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					                    ABBREVIATIONS AND ACRONYMS

    Ab        Antibody                   mo      Month
    Abn       Abnormal                   MRI     Magnetic resonance
    AFB       Acid-fast bacillus                   imaging
    Ag        Antigen                    N       Normal
    AIDS      Acquired immuno-           Neg     Negative
                deficiency syndrome       PCR     Polymerase chain reaction
    ALT       Alanine aminotransferase   NPO     Nothing by mouth
    ANA       Antinuclear antibody                 (nil per os)
    AST       Aspartate amino-           PO      Orally (per os)
                transferase              Pos     Positive
    CF        Complement fixation         PMN     Polymorphonuclear
    CHF       Congestive heart failure             neutrophil (leukocyte)
    CIE       Counterimmuno-             PTH     Parathyroid hormone
                electrophoresis          RBC     Red blood cell
    CK        Creatine kinase            RPR     Rapid plasma reagin
    CNS       Central nervous system               (syphilis test)
    CSF       Cerebrospinal fluid         s       Second
    CXR       Chest x-ray                SIADH   Syndrome of
    d         Day                                  inappropriate anti-
    Diff      Differential cell count              diuretic hormone
    EDTA      Ethylenediaminetetra-                (secretion)
                acetic acid (edetate)    SLE     Systemic lupus ery-
    ELISA     Enzyme-linked                        thematosus
                immunosorbent assay      T3      Triiodothyronine
    FT4I      Free thyroxine index       T4      Tetraiodothyronine
    GI        Gastrointestinal                     (thyroxine)
    GNR       Gram-negative rod          TSH     Thyroid-stimulating
    GNCB      Gram-negative                        hormone
                coccobacillus            V       Variable
    GPC       Gram-positive coccus       VDRL    Venereal Disease
    GVCB      Gram-variable                        Research Laboratory
                coccobacillus                      (syphilis test)
    h         Hour                       WBC     White blood cell
    Ig        Immunoglobulin             wk      Week
    IM        Intramuscular(ly)          yr      Year
    IV        Intravenous(ly)            ↑       Increased
    min       Minute                     ↓       Decreased
    MN        Mononuclear cell           ↔       No change



Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
Pocket Guide to
Diagnostic
Tests
third edition

Diana Nicoll, MD, PhD, MPA
Clinical Professor and Vice Chair
Department of Laboratory Medicine
University of California, San Francisco
Associate Dean
University of California, San Francisco
Chief of Staff and Chief, Laboratory Medicine Service
Veterans Affairs Medical Center, San Francisco

Stephen J. McPhee, MD
Professor of Medicine
Division of General Internal Medicine
University of California, San Francisco

Michael Pignone, MD, MPH
Assistant Professor of Medicine
University of North Carolina, Chapel Hill

William M. Detmer, MD, MS
Assistant Clinical Professor of Medicine
Department of Health Evaluation Sciences
University of Virginia, Charlottesville

Tony M. Chou, MD
Assistant Clinical Professor of Medicine
University of California, San Francisco

With Associate Authors

Lange Medical Books/McGraw-Hill
Medical Publishing Division
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McGraw-Hill
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DOI: 10.1036/0071373853
                                            Contents
        Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . Inside Front Cover
        Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
        1. Basic Principles of Diagnostic Test Use
           and Interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
           Diana Nicoll, MD, PhD, MPA,
           and Michael Pignone, MD, MPH
        2. Laboratory Procedures in the Clinical Setting . . . . . . . 23
           Stephen J. McPhee, MD
        3. Common Laboratory Tests:
           Selection and Interpretation . . . . . . . . . . . . . . . . . . . . . . 41
           Diana Nicoll, MD, PhD, MPA, Stephen J. McPhee, MD,
           and Michael Pignone, MD, MPH
        4. Therapeutic Drug Monitoring:
           Principles and Test Interpretation . . . . . . . . . . . . . . . . 187
           Diana Nicoll, MD, PhD, MPA
        5. Microbiology: Test Selection . . . . . . . . . . . . . . . . . . . . 195
           Mary K. York, PhD
        6. Diagnostic Imaging: Test Selection
           and Interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
           Sean Perini, MD, and Susan D. Wall, MD
        7. Basic Electrocardiography . . . . . . . . . . . . . . . . . . . . . . 283
           G. Thomas Evans, Jr., MD
        8. Diagnostic Testing: Algorithms, Nomograms,
           and Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
           Stephen J. McPhee, MD, Diana Nicoll, MD, PhD, MPA,
           and Michael Pignone, MD, MPH

        Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403

        Quick Reference Guide . . . . . . . . . . . . . . . . . . . . . . Back Cover




Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
                      Associate Authors
    G. Thomas Evans, Jr., MD
    Associate Clinical Professor of Medicine
    University of California, San Francisco
    Director of Electrocardiography
    Moffit-Long Hospitals, San Francisco
    Basic Electrocardiography
    Sean Perini, MD
    Clinical Fellow
    Section of Interventional Radiology
    Department of Radiology
    University of California, San Francisco
    Diagnostic Testing: Algorithms, Nomograms, and Tables
    Susan D. Wall, MD
    Professor of Radiology and Assistant Chief
    Department of Radiology
    Veterans Affairs Medical Center, San Francisco
    Associate Dean, Graduate Medical Education
    University of California, San Francisco
    Diagnostic Imaging: Test Selection and Interpretation
    Mary K. York, PhD
    Clinical Professor of Laboratory Medicine
    University of California, San Francisco
    Microbiology: Test Selection




Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
                                     Preface
        Purpose
             Pocket Guide to Diagnostic Tests is intended to serve as a pocket
        reference manual for medical and other health professional students,
        house officers, and practicing physicians. It is a quick reference guide
        to the selection and interpretation of commonly used diagnostic tests,
        including laboratory procedures in the clinical setting, laboratory tests
        (chemistry, hematology, and immunology), microbiology tests (bacte-
        riology, virology, and serology), diagnostic imaging tests (plain radi-
        ography, CT, MRI, and ultrasonography), and electrocardiography.
             This book will enable readers to understand commonly used
        diagnostic tests and diagnostic approaches to common disease states.
        Outstanding Features
         • Over 350 tests are presented in a concise, consistent, and readable
           format.
         • Fields covered include internal medicine, pediatrics, general
           surgery, neurology, and gynecology.
         • Costs and risks of various procedures and tests are emphasized.
         • Literature references are included for most diagnostic tests.
         • An index for quick reference is included on the back cover.
        Organization
              This pocket reference manual is not intended to include all diag-
        nostic tests or disease states. Rather, the authors have selected those
        tests and diseases that are most common and relevant to the general
        practice of medicine.
              The Guide is divided into eight sections:
          1. Basic Principles of Diagnostic Test Use and Interpretation
          2. Laboratory Procedures in the Clinical Setting
          3. Common Laboratory Tests: Selection and Interpretation
          4. Therapeutic Drug Monitoring: Principles and Test Interpretation
          5. Microbiology: Test Selection
          6. Diagnostic Imaging: Test Selection and Interpretation
          7. Basic Electrocardiography
          8. Diagnostic Testing: Algorithms, Nomograms, and Tables
        Intended Audience
              In this era of rapidly changing medical technology, many new
        diagnostic tests are being introduced every year and are replacing older
        tests as they are shown to be more sensitive, specific, or cost-effective.

Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
In this environment, students, house officers, and practicing physicians
are looking for a pocket reference on diagnostic tests.
      Medical students will find the concise summary of diagnostic labo-
ratory, microbiologic, and imaging studies, and of electrocardiography in
this pocket-sized book of great help during clinical ward rotations.
      Busy house officers will find the clear organization and citations
to the current literature useful in devising proper patient management.
      Practitioners (internists, family physicians, pediatricians, surgeons,
and other specialists who provide generalist care) may use the Guide as
a refresher manual to update their understanding of laboratory tests and
diagnostic approaches.
      Nurses and other health practitioners will find the format and
scope of the Guide valuable for understanding the use of laboratory
tests in patient management.
      In 1998, the contents of this book were integrated with the con-
tents of Pocket Guide to Commonly Prescribed Drugs, 2nd ed., by
Glenn N. Levine, MD, in a new CD-ROM, Current Medical Diagnosis
& Treatment 1998 on CD-ROM. An updated version of the CD-ROM,
including this book, will be published in 2000.
Acknowledgments
      We wish to thank our associate authors for their contributions to
this book. In addition, we are grateful to the many physicians, residents,
and students who contributed useful suggestions and to Jim Ransom for
his careful editing of the manuscript.
      We welcome comments and recommendations from our readers
for future editions.

                                           Diana Nicoll, MD, PhD, MPA
                                                Stephen J. McPhee, MD
                                            Michael Pignone, MD, MPH
                                           William M. Detmer, MD, MS
                                                    Tony M. Chou, MD

San Francisco
September 2000
                                                                               1
                     Basic Principles of Diagnostic
                      Test Use and Interpretation *




                    Diana Nicoll, MD, PhD, and Michael Pignone, MD, MPH




        The clinician’s main task is to make reasoned decisions about patient
        care despite incomplete clinical information and uncertainty about
        clinical outcomes. While data elicited from the history and physical
        examination are often sufficient for making a diagnosis or for guiding
        therapy, more information may be required. In these situations,
        clinicians often turn to diagnostic tests for help.


        BENEFITS; COSTS, AND RISKS
        When used appropriately, diagnostic tests can be of great assistance to
        the clinician. Tests can be helpful for screening, ie, to identify risk fac-
        tors for disease and to detect occult disease in asymptomatic persons.
        Identification of risk factors may allow early intervention to prevent
        disease occurrence, and early detection of occult disease may reduce


        *Chapter modified, with permission, from Tierney LM Jr, McPhee SJ, Papadakis MA

        (editors): Current Medical Diagnosis & Treatment 2000. McGraw-Hill, 2000.
                                              1
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
2     Pocket Guide to Diagnostic Tests

disease morbidity and mortality through early treatment. Optimal
screening tests meet the criteria listed in Table 1–1.
      Tests can also be helpful for diagnosis, ie, to help establish or
exclude the presence of disease in symptomatic persons. Some tests
assist in early diagnosis after onset of symptoms and signs; others assist
in differential diagnosis of various possible diseases; others help deter-
mine the stage or activity of disease.
      Finally, tests can be helpful in patient management. Tests
can help (1) evaluate the severity of disease, (2) estimate prognosis,
(3) monitor the course of disease (progression, stability, or resolution),
(4) detect disease recurrence, and (5) select drugs and adjust therapy.
      When ordering diagnostic tests, clinicians should weigh the poten-
tial benefits against the potential costs and disadvantages:

    (1) Some tests carry a risk of morbidity or mortality—eg, cerebral
        angiogram leads to stroke in 1% of cases.
    (2) The discomfort associated with tests such as sigmoidoscopy or
        barium enema will deter some patients from completing a
        diagnostic work-up.
    (3) The result of a diagnostic test often has implications for further
        care in that a test result may mandate further testing or frequent
        follow-up. This means that a patient with a positive fecal occult
        blood test may incur significant cost, risk, and discomfort during
        follow-up sigmoidoscopy, barium enema, or colonoscopy.
    (4) A false-positive test may lead to further unnecessary testing.
        Classifying a healthy patient as diseased based on a falsely
        positive diagnostic test can cause psychologic distress and may
        lead to risks from unnecessary therapy.

                   TABLE 1–1. CRITERIA FOR USE OF
                   SCREENING PROCEDURES.

                    Characteristics of population
                       1. Sufficiently high prevalence of disease.
                       2. Likely to be compliant with subsequent tests
                          and treatments.
                    Characteristics of disease
                       1. Significant morbidity and mortality.
                       2. Effective and acceptable treatment available.
                       3. Presymptomatic period detectable.
                       4. Improved outcome from early treatment.
                    Characteristics of test
                       1. Good sensitivity and specificity.
                       2. Low cost and risk.
                       3. Confirmatory test available and practical.
                   Basic Principles of Diagnostic Test Use and Interpretation   3

  (5) A diagnostic or screening test may identify cases of disease that
      would not otherwise have been recognized and that would not
      have affected the patient. For example, early-stage, low-grade
      prostate cancer detected by PSA screening in an 84-year-old man
      with known severe congestive heart failure will probably not
      become symptomatic or require treatment during his lifetime.
  (6) An individual test such as MRI of the head can cost more than
      $1400, and diagnostic tests as a whole account for approximately
      one-fifth of health care expenditures in the USA.


PERFORMANCE OF DIAGNOSTIC TESTS
Factors affecting both the patient and the specimen are important. The
most crucial element in a properly conducted laboratory test is an
appropriate specimen.

Patient Preparation
Preparation of the patient is important for certain tests—eg, a fasting
state is needed for optimal glucose and triglyceride measurements; pos-
ture and sodium intake must be strictly controlled when measuring
renin and aldosterone levels; and strenuous exercise should be avoided
before taking samples for creatine kinase determinations, since vigor-
ous muscle activity can lead to falsely abnormal results.

Specimen Collection
Careful attention must be paid to patient identification and specimen
labeling. Knowing when the specimen was collected may be important.
For instance, aminoglycoside levels cannot be interpreted appropriately
without knowing whether the specimen was drawn just before
(“trough” level) or after (“peak” level) drug administration. Drug lev-
els cannot be interpreted if they are drawn during the drug’s distribu-
tion phase (eg, digoxin levels drawn during the first 6 hours after an oral
dose). Substances that have a circadian variation (eg, cortisol) can be
interpreted only in the context of the time of day the sample was drawn.
     During specimen collection, other principles should be remem-
bered. Specimens should not be drawn above an intravenous line, as this
may contaminate the sample with intravenous fluid. Excessive tourni-
quet time will lead to hemoconcentration and an increased concentra-
tion of protein-bound substances such as calcium. Lysis of cells during
collection of a blood specimen will result in spuriously increased serum
4     Pocket Guide to Diagnostic Tests

levels of substances concentrated in cells (eg, lactate dehydrogenase
and potassium). Certain test specimens may require special handling or
storage (eg, blood gas specimens). Delay in delivery of specimens to
the laboratory can result in ongoing cellular metabolism and therefore
spurious results for some studies (eg, low blood glucose).


TEST CHARACTERISTICS
Table 1–2 lists the general characteristics of useful diagnostic tests.
Most of the principles detailed below can be applied not only to labo-
ratory and radiologic tests but also to elements of the history and phys-
ical examination.

Accuracy
The accuracy of a laboratory test is its correspondence with the true
value. An inaccurate test is one that differs from the true value even
though the results may be reproducible (Figures 1–1A and 1–1B). In
the clinical laboratory, accuracy of tests is maximized by calibrating
laboratory equipment with reference material and by participation in
external quality control programs.

Precision
Test precision is a measure of a test’s reproducibility when repeated on
the same sample. An imprecise test is one that yields widely varying
results on repeated measurements (Figure 1–1B). The precision of diag-
nostic tests, which is monitored in clinical laboratories by using control
material, must be good enough to distinguish clinically relevant
changes in a patient’s status from the analytic variability of the test. For
instance, the manual white blood cell differential count is not precise

TABLE 1–2. PROPERTIES OF USEFUL DIAGNOSTIC TESTS.

 1. Test methodology has been described in detail so that it can be accurately and reliably reproduced.
 2. Test accuracy and precision have been determined.
 3. The reference range has been established appropriately.
 4. Sensitivity and specificity have been reliably established by comparison with a gold standard.
    The evaluation has used a range of patients, including those who have different but commonly
    confused disorders and those with a spectrum of mild and severe, treated and untreated disease.
    The patient selection process has been adequately described so that results will not be
    generalized inappropriately.
 5. Independent contribution to overall performance of a test panel has been confirmed if a test is
    advocated as part of a panel of tests.
                         Basic Principles of Diagnostic Test Use and Interpretation            5




             A                                 B                                C


Figure 1–1. Relationship between accuracy and precision in diagnostic tests. The center of
the target represents the true value of the substance being tested. Figure (A) represents a diag-
nostic test which is precise but inaccurate; on repeated measurement, the test yields very sim-
ilar results, but all results are far from the true value. Figure (B) shows a test which is
imprecise and inaccurate; repeated measurement yields widely different results, and the
results are far from the true value. Figure (C) shows an ideal test, one that is both precise and
accurate.


enough to detect important changes in the distribution of cell types,
because it is calculated by subjective evaluation of a small sample (100
cells). Repeated measurements by different technicians on the same
sample result in widely different results. Automated differential counts
are more precise because they are obtained from machines that use
objective physical characteristics to classify a much larger sample
(10,000 cells).

Reference Range
Reference ranges are method- and laboratory-specific. In practice, they
often represent test results found in 95% of a small population presumed
to be healthy; by definition, then, 5% of healthy patients will have a pos-
itive (abnormal) test (Figure 1–2). As a result, slightly abnormal results
should be interpreted critically—they may be either truly abnormal or
falsely abnormal. The practitioner should be aware also that the more
tests ordered, the greater the chance of obtaining a falsely abnormal
result. For a healthy person subjected to 20 independent tests, there is a
64% chance that one test result will lie outside the reference range (Table
1–3). Conversely, values within the reference range may not rule out the
actual presence of disease since the reference range does not establish the
distribution of results in patients with disease.
      It is important to consider also whether published reference ranges
are appropriate for the patient being evaluated, since some ranges
depend on age, sex, weight, diet, time of day, activity status, or posture.
For instance, the reference ranges for hemoglobin concentration are age-
6    Pocket Guide to Diagnostic Tests




                individuals tested
                    Number of




                                          -2   -1 Mean 1 2
                            Abnormal             Normal          Abnormal
                             (2.5%)               (95%)           (2.5%)
                                               Test results
                                          (percent of population)

Figure 1–2. The reference range is usually defined as within 2 standard deviations of the mean
test result (shown as –2 and 2) in a small population of healthy volunteers. Note that in this
example, test results are normally distributed; however, many biologic substances will have
distributions that are skewed.


and sex-dependent. Chapter 3 contains the reference ranges for com-
monly used chemistry and hematology tests. Test performance charac-
teristics such as sensitivity and specificity are needed to interpret results
and are discussed below.

Interfering Factors
The results of diagnostic tests can be altered by external factors, such
as ingestion of drugs; and internal factors, such as abnormal physiologic
states.
     External interferences can affect test results in vivo or in vitro. In
vivo, alcohol increases γ-glutamyl transpeptidase, and diuretics can affect


     TABLE 1–3. RELATIONSHIP BETWEEN THE NUMBER OF TESTS AND THE
     PROBABILITY THAT A HEALTHY PERSON WILL HAVE ONE OR MORE
     ABNORMAL RESULTS.

                                                     Probability That One or More Results
                Number of Tests                                Will Be Abnormal
                                      1                               5%
                                      6                             26%
                                     12                             46%
                                     20                             64%
                    Basic Principles of Diagnostic Test Use and Interpretation   7

sodium and potassium concentrations. Cigarette smoking can induce
hepatic enzymes and thus reduce levels of substances such as theo-
phylline that are metabolized by the liver. In vitro, cephalosporins may
produce spurious serum creatinine levels due to interference with a com-
mon laboratory method.
     Internal interferences result from abnormal physiologic states
interfering with the test measurement. As an example, patients with
gross lipemia may have spuriously low serum sodium levels if the test
methodology used includes a step in which serum is diluted before
sodium is measured. Because of the potential for test interference, clin-
icians should be wary of unexpected test results and should investigate
reasons other than disease that may explain abnormal results, including
laboratory error.

Sensitivity and Specificity
Clinicians should use measures of test performance such as sensitiv-
ity and specificity to judge the quality of a diagnostic test for a par-
ticular disease. Test sensitivity is the likelihood that a diseased patient
has a positive test. If all patients with a given disease have a positive
test (ie, no diseased patients have negative tests), the test sensitivity
is 100%. A test with high sensitivity is useful to exclude a diagnosis
because a highly sensitive test will render few results that are falsely
negative. To exclude infection with the AIDS virus, for instance, a
clinician might choose a highly sensitive test such as the HIV anti-
body test.
      A test’s specificity is the likelihood that a healthy patient has a
negative test. If all patients who do not have a given disease have neg-
ative tests (ie, no healthy patients have positive tests), the test specificity
is 100%. A test with high specificity is useful to confirm a diagnosis,
because a highly specific test will have few results that are falsely pos-
itive. For instance, to make the diagnosis of gouty arthritis, a clinician
might choose a highly specific test, such as the presence of negatively
birefringent needle-shaped crystals within leukocytes on microscopic
evaluation of joint fluid.
      To determine test sensitivity and specificity for a particular dis-
ease, the test must be compared against a “gold standard,” a procedure
that defines the true disease state of the patient. For instance, the sensi-
tivity and specificity of the ventilation/perfusion scan for pulmonary
embolus are obtained by comparing the results of scans with the gold
standard, pulmonary arteriography. Application of the gold standard
examination to patients with positive scans establishes specificity. Fail-
ure to apply the gold standard examination following negative scans
8     Pocket Guide to Diagnostic Tests

may result in an overestimation of sensitivity, since false negatives will
not be identified. However, for many disease states (eg, pancreatitis),
such a gold standard either does not exist or is very difficult or expen-
sive to apply. Therefore, reliable estimates of test sensitivity and speci-
ficity are sometimes difficult to obtain.
      Sensitivity and specificity can also be affected by the population
from which these values are derived. For instance, many diagnostic tests
are evaluated first using patients who have severe disease and control
groups who are young and well. Compared with the general population,
this study group will have more results that are truly positive (because
patients have more advanced disease) and more results that are truly
negative (because the control group is healthy). Thus, test sensitivity
and specificity will be higher than would be expected in the general pop-
ulation, where more of a spectrum of health and disease are found. Clin-
icians should be aware of this spectrum bias when generalizing
published test results to their own practice.
      Test sensitivity and specificity depend on the threshold above
which a test is interpreted to be abnormal (Figure 1–3). If the threshold
is lowered, sensitivity is increased at the expense of lowered specificity,
or vice versa.
      Figure 1–4 shows how test sensitivity and specificity can be cal-
culated using test results from patients previously classified by the gold
standard as diseased or nondiseased.


                                        No
                individuals tested




                                     disease                         Disease
                   Number of




                                               A         B C
                                                Test results

Figure 1–3. Hypothetical distribution of test results for healthy and diseased individuals. The
position of the “cutoff point” between “normal” and “abnormal” (or “negative” and “positive”)
test results determines the test’s sensitivity and specificity. If point “A” is the cutoff point, the
test would have 100% sensitivity but low specificity. If point “C” is the cutoff point, the test would
have 100% specificity but low sensitivity. For most tests, the cutoff point is determined by the
reference range, ie, the range of test results that are within 2 standard deviations of the mean
(point “B”). In some situations, the cutoff is altered to enhance either sensitivity or specificity.
                          Basic Principles of Diagnostic Test Use and Interpretation           9


                     Disease
                 Present Absent

    Positive         TP           FP        TP = (Sensitivity)(Pretest probability)
                                            FP = (1–Specificity)(1–Pretest probability)
 Test




                                            FN = (1–Sensitivity)(Pretest probability)
                                            TN = (Specificity)(1–Pretest probability)
   Negative          FN           TN



                              Number of diseased
                              patients with positive test                          TP
         Sensitivity =                                                 =
                            Number of diseased patients                        TP + FN


                                Number of nondiseased
                                patients with negative test                       TN
         Specificity =                                                 =
                            Number of nondiseased patients                     TN + FP


  Posttest                                                                         TP
  probability after =      Probability of disease if test positive =
  positive test                                                                 TP + FP

                            (Sensitivity)(Pretest probability)
                      =
                            (Sensitivity)(Pretest probability) +
                            (1–Specificity)(1–Pretest probability)



Figure 1–4. Calculation of sensitivity, specificity, and probability of disease after a positive
test (posttest probability). (TP, true positive; FP, false positive; FN, false negative; TN, true
negative.)


     The performance of two different tests can be compared by plotting
the sensitivity and (1 minus the specificity) of each test at various refer-
ence range cutoff values. The resulting receiver operator characteris-
tic (ROC) curve will often show which test is better; a clearly superior
test will have an ROC curve that always lies above and to the left of the
inferior test curve, and, in general, the better test will have a larger area
under the ROC curve. For instance, Figure 1–5 shows the ROC curves
for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP)
in the diagnosis of prostate cancer. PSA is a superior test because it has
higher sensitivity and specificity for all cutoff values.
10     Pocket Guide to Diagnostic Tests

                       1
                                                                                                1
                      .9                                                         2
                                                                    4
                                                                                          0.2
                      .8
                                                    6
                      .7
        Sensitivity




                      .6                 10                             0.3
                      .5
                                                   0.4
                                                                               PSA µg/L
                      .4       20
                      .3                                                       PAP U/L
                                    0.6
                                 0.8
                      .2
                               1.2
                      .1
                           0        .1        .2         .3    .4         .5     .6      .7         .8
                                                         1 – Specificity

Figure 1–5. Receiver operator characteristic (ROC) curves for prostate-specific antigen (PSA)
and prostatic acid phosphatase (PAP) in the diagnosis of prostate cancer. For all cutoff val-
ues, PSA has higher sensitivity and specificity; therefore, it is a better test based on these per-
formance characteristics. (Modified and reproduced, with permission, from Nicoll D et al:
Routine acid phosphatase testing for screening and monitoring prostate cancer no longer jus-
tified. Clin Chem 1993;39:2540.)



USE OF TESTS IN DIAGNOSIS AND MANAGEMENT
The value of a test in a particular clinical situation depends not only on
the test’s sensitivity and specificity but also on the probability that the
patient has the disease before the test result is known (pretest prob-
ability). The results of a valuable test will substantially change the
probability that the patient has the disease (posttest probability).
Figure 1–4 shows how posttest probability can be calculated from the
known sensitivity and specificity of the test and the estimated pretest
probability of disease (or disease prevalence).
     The pretest probability of disease has a profound effect on the
posttest probability of disease. As demonstrated in Table 1–4, when a
test with 90% sensitivity and specificity is used, the posttest probabil-
ity can vary from 1% to 99% depending on the pretest probability of
disease. Furthermore, as the pretest probability of disease decreases, it
becomes less likely that someone with a positive test actually has the
disease and more likely that the result represents a false positive.
                  Basic Principles of Diagnostic Test Use and Interpretation   11

              TABLE 1–4. INFLUENCE OF PRETEST PROBABILITY ON
              THE POSTTEST PROBABILITY OF DISEASE WHEN A
              TEST WITH 90% SENSITIVITY AND 90% SPECIFICITY
              IS USED.

                  Pretest Probability      Posttest Probability

                         0.01                      0.08
                         0.50                      0.90
                         0.99                      0.999




      As an example, suppose the clinician wishes to calculate the
posttest probability of prostate cancer using the PSA test and a cut-off
value of 4 ng/mL. Using the data shown in Figure 1–5, sensitivity is
90% and specificity is 60%. The clinician estimates the pretest proba-
bility of disease given all the evidence and then calculates the posttest
probability using the approach shown in Figure 1–5. The pretest
probability that an otherwise healthy 50-year-old man has prostate
cancer is equal to the prevalence of prostate cancer in that age group
(probability = 10%) and the posttest probability is only 20%—ie, even
though the test is positive, there is still an 80% chance that the patient
does not have prostate cancer (Figure 1–6A). If the clinician finds a
prostate nodule on rectal examination, the pretest probability of prostate
cancer rises to 50% and the posttest probability using the same test is
69% (Figure 1–6B). Finally, if the clinician estimates the pretest
probability to be 98% based on a prostate nodule, bone pain, and lytic
lesions on spine x-rays, the posttest probability using PSA is 99%
(Figure 1–6C). This example illustrates that pretest probability has a
profound effect on posttest probability and that tests provide more infor-
mation when the diagnosis is truly uncertain (pretest probability about
50%) than when the diagnosis is either unlikely or nearly certain.

ODDS-LIKELIHOOD RATIOS
An easier way to calculate the posttest probability of disease is to use
the odds-likelihood approach. Sensitivity and specificity are combined
into one entity called the likelihood ratio (LR).

                      Probability of result in diseased persons
             LR =
                    Probability of result in nondiseased persons
      Every test has two likelihood ratios, one corresponding to a posi-
tive test (LR+) and one corresponding to a negative test (LR−):
12       Pocket Guide to Diagnostic Tests


A
  Pretest
 probability      Posttest
                 probability

           Positive
            test



     0                                   .5                                     1
                               Probability of disease

                                     Pretest
                                    probability    Posttest
B                                                 probability

                                            Positive
                                             test



     0                                   .5                                     1
                               Probability of disease

                                                                   Pretest
                                                                  probability    Posttest
                                                                                probability
C


     0                                   .5                                     1
                               Probability of disease

Figure 1–6. Effect of pretest probability and test sensitivity and specificity on the posttest
probability of disease. (See text for explanation.)


                        Probability that test is positive in diseased persons
           LR + =
                      Probability that test is positive in nondiseased persons

                        Sensitivity
                 =
                      1 − Specificity

                        Probability that test is negative in diseased persons
           LR − =
                      Probability that test is negative in nondiseased persons

                      1 − Sensitivity
                 =
                        Specificity
                          Basic Principles of Diagnostic Test Use and Interpretation     13

     Lists of likelihood ratios can be found in some textbooks, journal
articles, and computer programs (see Table 1–5 for sample values).
Likelihood ratios can be used to make quick estimates of the usefulness
of a contemplated diagnostic test in a particular situation. The simplest
method for calculating posttest probability from pretest probability and
likelihood ratios is to use a nomogram (Figure 1–7). The clinician
places a straightedge through the points that represent the pretest prob-
ability and the likelihood ratio and then reads the posttest probability
where the straightedge crosses the posttest probability line.


 TABLE 1–5. LIKELIHOOD RATIOS (LR) FOR DIAGNOSTIC TESTS.

                   Test                              Disease               LR+    LR−

  Amylase (↑)                                Pancreatitis                   9.1   0.2
  Anti-dsDNA (↑)                             SLE                           37     0.28
  Antinuclear antibody                       SLE                            4.5   0.13
  Carcinoembryonic antigen                   Dukes A colon cancer           1.6   0.87
  Creatine kinase MB                         Myocardial infarction         32     0.05
  Esophagogastroduodenoscopy (+)             Upper GI bleeding             18     0.11
  ESR > 30 mm/h                              Temporal arteritis             3.3   0.01
  Exercise echocardiography                  Coronary artery disease        6.2   0.23
    (new wall motion abnormalities)
  Exercise ECG (ST depression > 1 mm)        Coronary artery disease        5.9   0.39
  Ferritin                                   Iron deficiency anemia         85     0.15
  Free T4 (↑)                                Hyperthyroidism               19     0.05
  Free thyroxine index                       Hyperthyroidism                6.8   0.06
  Hepatitis A IgM antibody                   Hepatitis A                   99     0.01
  Heterophil (+)                             Infectious mononucleosis      97     0.03
  Metanephrines (↑)                          Pheochromocytoma              11     0.23
  Pleural fluid protein > 3 g/dL              Exudative pleural effusion    10     0.12
  Technetium Tc 99m pyrophosphate scan       Myocardial infarction        > 360   0.64
    (highly focal uptake)
  Testosterone (↓)                           Erectile dysfunction          32     0.03
  TSH (↑)                                    Hypothyroidism                99     0.01
  24-Hour urinary free cortisol (↑)          Hypercortisolism              10     0.07
14     Pocket Guide to Diagnostic Tests


                           .1                                      99

                           .2


                           .5                                      95

                            1          1000                        90
                                        500
                            2           200                        80
                                        100
                                         50                        70
                            5
                                          20                       60
                                          10                       50
                           10
                                           5                       40

                          20               2                       30
                   %                       1                              %
                          30                                       20
                                                  .5
                          40                      .2
                                                                   10
                          50                      .1
                          60                      .05
                                                                   5
                          70                      .02
                                                  .01
                          80                      .005             2
                                                  .002
                          90                      .001             1

                          95                                       .5


                                                                   .2

                         99                                      .1
                      Pretest             Likelihood           Posttest
                     probability             ratio            probability

Figure 1–7. Nomogram for determining posttest probability from pretest probability and likeli-
hood ratios. To figure the posttest probability, place a straightedge between the pretest pro-
bability and the likelihood ratio for the particular test. The posttest probability will be where
the straightedge crosses the posttest probability line. (Adapted and reproduced, with per-
mission, from Fagan TJ: Nomogram for Bayes’s theorem. N Engl J Med 1975;293:257.)
                   Basic Principles of Diagnostic Test Use and Interpretation   15

     A more formal way of calculating posttest probabilities uses the
likelihood ratio as follows:
               Pretest odds × Likelihood ratio = Posttest odds

     To use this formulation, probabilities must be converted to odds,
where the odds of having a disease are expressed as the chance of hav-
ing the disease divided by the chance of not having the disease. For
instance, a probability of 0.75 is the same as 3 1 odds (Figure 1–8).
     To estimate the potential benefit of a diagnostic test, the clinician
first estimates the pretest odds of disease given all available clinical
information and then multiplies the pretest odds by the positive and
negative likelihood ratios. The results are the posttest odds, or the odds
that the patient has the disease if the test is positive or negative. To
obtain the posttest probability, the odds are converted to a probability
(Figure 1–8).
     For example, if the clinician believes that the patient has a 60%
chance of having a myocardial infarction (pretest odds of 3 2) and the
creatine kinase MB test is positive (LR+ = 32), then the posttest odds of
having a myocardial infarction are


                         Probability
        Odds =
                       1 – Probability

               Example: If probability = 0.75, then

                                 0.75                0.75           3
               Odds =                        =                  =       = 3:1
                               1 – 0.75              0.25           1

                             Odds
        Probability =
                            Odds + 1

               Example: If odds = 3:1, then

                                      3/1                   3
              Probability =                      =                  = 0.75
                                   3/1 + 1              3+1


         Figure 1–8. Formulas for converting between probability and odds.
16     Pocket Guide to Diagnostic Tests


     3        96               48 1      48                     
       × 32 =    or 48 1 odds          =       = 96% probability
     2        2                48 1 + 1 48 + 1                  

If the CKMB test is negative (LR− = 0.05), then the posttest odds of
having a myocardial infarction are

     3          0.15       0.15 2       0.15                   
       × 0.05 =      odds            =         = 7% probability
     2           2         0.15 2 + 1 0.15 + 2                 

Sequential Testing
To this point, the impact of only one test on the probability of disease
has been discussed, whereas during most diagnostic workups, clinicians
obtain clinical information in a sequential fashion. To calculate the
posttest odds after three tests, for example, the clinician might estimate
the pretest odds and use the appropriate likelihood ratio for each test:
                Pretest odds × LR1 × LR 2 × LR 3 = Posttest odds

When using this approach, however, the clinician should be aware of a
major assumption: the chosen tests or findings must be conditionally
independent. For instance, with liver cell damage, the aspartate amino-
transferase (AST) and alanine aminotransferase (ALT) enzymes may
be released by the same process and are thus not conditionally inde-
pendent. If conditionally dependent tests are used in this sequential
approach, an overestimation of posttest probability will result.

Threshold Approach to Decision Making
A key aspect of medical decision making is the selection of a treatment
threshold, ie, the probability of disease at which treatment is indicated.
Figure 1–9 shows a possible way of identifying a treatment threshold by
considering the value (utility) of the four possible outcomes of the
treat/don’t treat decision.
      A diagnostic test is useful only if it shifts the disease probability
across the treatment threshold. For example, a clinician might decide
to treat with antibiotics if the probability of streptococcal pharyngitis
in a patient with a sore throat is greater than 25% (Figure 1–10A). If,
after reviewing evidence from the history and physical examination,
the clinician estimates the pretest probability of strep throat to be 15%,
then a diagnostic test such as throat culture (LR+ = 7) would be useful
only if a positive test would shift the posttest probability above 25%.
Use of the nomogram shown in Figure 1–7 indicates that the posttest
                         Basic Principles of Diagnostic Test Use and Interpretation             17




Figure 1–9. The “treat/don’t treat” threshold. (A) Patient does not have disease and is not
treated (highest utility). (B) Patient does not have disease and is treated (lower utility than A).
(C) Patient has disease and is treated (lower utility than A). (D) Patient has disease and is not
treated (lower utility than C).




probability would be 55% (Figure 1–10B); thus, ordering the test
would be justified as it affects patient management. On the other hand,
if the history and physical examination had suggested that the pretest
probability of strep throat was 60%, the throat culture (LR− = 0.33)
would be indicated only if a negative test would lower the posttest
probability below 25%. Using the same nomogram, the posttest prob-
ability after a negative test would be 33% (Figure 1–10C). Therefore,
ordering the throat culture would not be justified.
      This approach to decision making is now being applied in the clin-
ical literature.

Decision Analysis
Up to this point, the discussion of diagnostic testing has focused on test
characteristics and methods for using these characteristics to calculate
the probability of disease in different clinical situations. Although use-
ful, these methods are limited because they do not incorporate the many
outcomes that may occur in clinical medicine or the values that patients
and clinicians place on those outcomes. To incorporate outcomes and
values with characteristics of tests, decision analysis can be used.
      The basic idea of decision analysis is to model the options in a
medical decision, assign probabilities to the alternative actions, assign
values (utilities) to the various outcomes, and then calculate which deci-
sion gives the greatest value. To complete a decision analysis, the clin-
ician would proceed as follows:
18       Pocket Guide to Diagnostic Tests


A                Treat/don't treat
                    threshold




          Don't treat                                    Treat


     0                                       .5                                          1
                                 Probability of disease



           Pretest
B                                                  Posttest
          probability
                                                  probability

                                Positive
                                 test




          Don't treat                                    Treat


     0                                       .5                                          1
                                 Probability of disease


                                                    Pretest
                          Posttest                 probability
C                        probability

                                       Negative
                                         test




          Don't treat                                    Treat


     0                                       .5                                          1
                                 Probability of disease

Figure 1–10. Threshold approach applied to test ordering. If the contemplated test will not
change patient management, the test should not be ordered. (See text for explanation.)
                        Basic Principles of Diagnostic Test Use and Interpretation           19

   (1) Draw a decision tree showing the elements of the medical decision.
   (2) Assign probabilities to the various branches.
   (3) Assign values (utilities) to the outcomes.
   (4) Determine the expected utility (the product of probability and
       utility) of each branch.
   (5) Select the decision with the highest expected utility.

Figure 1–11 shows a decision tree where the decision to be made is
whether to treat without testing, perform a test and then treat based on
the test result, or perform no tests and give no treatment. The clinician




Figure 1–11. Generic tree for a clinical decision where the choices are (1) to treat the patient
empirically, (2) to test and then treat if the test is positive, or (3) to withhold therapy. The
square node is called a decision node, and the round nodes are called chance nodes.
(p, pretest probability of disease; Sens, sensitivity; Spec, specificity.)
20   Pocket Guide to Diagnostic Tests

begins the analysis by building a decision tree showing the important
elements of the decision. Once the tree is built, the clinician assigns
probabilities to all the branches. In this case, all the branch probabili-
ties can be calculated from (1) the probability of disease before the
test (pretest probability), (2) the chance of a positive test if the dis-
ease is present (sensitivity), and (3) the chance of a negative test if the
disease is absent (specificity). Next, the clinician assigns utility val-
ues to each of the outcomes.
     After the expected utility is calculated, the clinician may identify
which alternative has the highest value by this analysis.
     Although time-consuming, decision analysis can help to structure
complex clinical problems and to make difficult clinical decisions.

Evidence-Based Medicine
The focus over the past decade on evidence-based medicine stresses
the examination of evidence from clinical research—rather than intu-
ition and pathophysiologic reasoning—as a basis for clinical decision
making. Evidence-based medicine relies on systematic reviews of the
medical literature to inform clinical practice. Meta-analysis uses statis-
tical techniques to combine evidence from different studies.
      Clinical practice guidelines are systematically developed state-
ments intended to assist practitioners and patients in making decisions
about health care. Clinical algorithms and practice guidelines are now
ubiquitous in medicine. Their utility and validity depend on the quality
of the evidence that shaped the recommendations, on their being kept
current, and on their acceptance and appropriate application by clini-
cians. While clinicians are concerned about the effect of guidelines on
professional autonomy, many organizations are trying to use compli-
ance with practice guidelines as a measure of quality of care.

Computer Access to Medical Information
The development of medical information science and computer tech-
nology now offer a vast amount of clinical information on CD-ROM or
over the World Wide Web.


REFERENCES
Dekay ML, Asch DA: Is the defensive use of diagnostic tests good for
    patients, or bad? Med Decis Making 1998;18:19.
Detsky AS et al: Primer on medical decision analysis. (Five parts.) Med
    Decis Making 1997;17:123.
                 Basic Principles of Diagnostic Test Use and Interpretation   21

Jadad AR, Haynes RB: The Cochrane collaboration: Advances and
    challenges in improving evidence-based decision making. Med
    Decis Making 1998;18:2.
Maynard A: Evidence-based medicine: An incomplete method for
    informing treatment choices. Lancet 1997;349:126.
Panzer RJ, Black ER, Griner PF (editors): Diagnostic Strategies
    for Common Medical Problems, 2nd ed. American College of
    Physicians, 1999.
Sackett DL et al: Clinical Epidemiology. A Basic Science for Clinical
    Medicine, 2nd ed. Little, Brown, 1991.
Sox HC: The evaluation of diagnostic tests: Principles, problems, and
    new developments. Annu Rev Med 1996;47:463.
Tugwell P et al: Laboratory evaluation in the diagnosis of Lyme
    disease. Ann Intern Med 1997;127:1109. (Sensitivity, specificity,
    likelihood ratios, and pretest and posttest probabilities used to
    formulate guidelines for clinical diagnosis of Lyme disease.)
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                                                                                                 2
                                           Laboratory Procedures
                                            in the Clinical Setting




                                                                       Stephen J. McPhee, MD




        This chapter presents information on how to perform common bedside
        laboratory procedures. Information on interpretation of results of body
        fluid analysis is included in some of the sections. Test results can be
        used for patient care only if the tests have been performed according to
        strict federal guidelines.

        Contents                                                                                 Page
        1. Obtaining and processing body fluids...........................................24
            A. Safety considerations...........................................................24
            B. Specimen handling ..............................................................24
        2. Basic staining methods .................................................................25
             A. Gram stain ...........................................................................25
             B. Wright stain of peripheral blood smear...............................27
        3. Other bedside laboratory procedures ............................................28
             A. Urinalysis ............................................................................28
             B. Vaginal fluid wet preparation..............................................33
             C. Skin or vaginal fluid KOH preparation ...............................33
             D. Synovial fluid examination for crystals...............................35
             E. Pulse oximetry.....................................................................36
                                                       23
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
24      Pocket Guide to Diagnostic Tests

1. OBTAINING AND PROCESSING BODY FLUIDS
     A. Safety Considerations
        General Safety Considerations
           Because all patient specimens are potentially infectious, the
           following precautions should be observed:
           a. Universal body fluid and needle stick precautions must be
              observed at all times.
           b. Disposable gloves and sometimes gown, mask, and gog-
              gles should be worn when collecting specimens.
           c. Gloves should be changed and hands washed after contact
              with each patient. Dispose of gloves in an appropriate bio-
              hazard waste container.
           d. Any spills should be cleaned up with 10% bleach solution.
        Handling and Disposing of Needles and Gloves
           a. Do not resheath needles.
           b. Discard needles and gloves only into designated containers.
           c. Do not remove a used needle from a syringe by hand.
              The needle may be removed using a specially designed
              waste collection system, or the entire assembly may (if
              disposable) be discarded as a unit into a designated
              container.
           d. When obtaining blood cultures, it is hazardous and unnec-
              essary to change needles.
           e. Do not place phlebotomy or other equipment on the pa-
              tient’s bed.
     B. Specimen Handling
        Identification of Specimens
           a. Identify the patient before obtaining the specimen. (If the
               patient is not known to you, ask for the name and check the
               wristband.)
           b. Label each specimen container with the patient’s name and
               identification number.
        Specimen Tubes: Standard specimen tubes are now widely
        available and are easily identified by the color of the stopper (see
        also p 37):
           a. Red-top tubes contain no anticoagulants or preservatives
               and are used for chemistry tests.
           b. Marbled-top tubes contain material that allows ready
               separation of serum and clot by centrifugation.
           c. Lavender-top tubes contain EDTA and are used for hema-
               tology tests (eg, blood or cell counts, differentials).
                           Laboratory Procedures in the Clinical Setting   25

       d. Green-top tubes contain heparin and are used for tests that
          require plasma or anticoagulation.
       e. Blue-top tubes contain citrate and are used for coagulation
          tests.
       f. Gray-top tubes contain fluoride and are used for some che-
          mistry tests (eg, glucose) if the specimen cannot be ana-
          lyzed immediately.
    Procedure
       a. When collecting multiple specimens, fill sterile tubes used
          for bacteriologic tests, then tubes without additives (ie,
          red-top tubes) before filling those with additives to avoid
          the potential for bacterial contamination, transfer of anti-
          coagulants, etc. However, be certain to fill tubes contain-
          ing anticoagulants before the blood specimen clots.
       b. The recommended order of filling tubes is (by type and
          color): (1) blood culture, (2) red top, (3) blue top, (4) green
          top, (5) lavender top.
       c. Fill each stoppered tube completely. Tilt each tube con-
          taining anticoagulant or preservative to mix thoroughly.
          Place any specimens on ice as required (eg, arterial blood).
          Deliver specimens to the laboratory promptly.
       d. For each of the major body fluids, Table 2–1 summarizes
          commonly requested tests and requirements for specimen
          handling and provides cross-references to tables and fig-
          ures elsewhere in this book for help in interpretation of the
          results.


2. BASIC STAINING METHODS
 A. Gram Stain
    Preparation of Smear
       a. Obtain a fresh specimen of the material to be stained (eg,
          sputum) and smear a small amount on a glass slide. Thin
          smears give the best results (eg, press a sputum sample
          between two glass slides).
       b. Let the smear air-dry before heat-fixing, because heating a
          wet smear will usually distort cells and organisms.
       c. Heat-fix the smear by passing the clean side of the slide
          quickly through a Bunsen burner or other flame source (no
          more than three or four times). The slide should be warm,
          not hot.
       d. Let the slide cool before staining.
26       Pocket Guide to Diagnostic Tests

TABLE 2–1. BODY FLUID TESTS, HANDLING, AND INTERPRETATION.

                        Commonly               Specimen Tube and            Interpretation
 Body Fluid           Requested Tests               Handling                    Guide

 Arterial blood   pH, PO2, PCO2               Glass syringe. Evacuate air   See acid-base
                                               bubbles; remove needle;       nomogram
                                               position rubber cap; place    p 337.
                                               sample on ice; deliver
                                               immediately.
 Ascitic fluid     Cell count, differential    Lavender top                  See ascitic fluid
                  Protein, amylase            Red top                        profiles, p 365.
                  Gram stain, culture         Sterile
                  Cytology (if neoplasm       Cytology
                   suspected)
 Cerebrospinal    Cell count, differential    Tube #1                       See cerebrospinal
  fluid            Gram stain, culture         Tube #2                        fluid profiles,
                  Protein, glucose            Tube #3                        p 369.
                  VDRL or other studies       Tube #4
                   (oligoclonal bands)
                  Cytology (if neoplasm       Cytology
                   suspected)
 Pleural fluid     Cell count, differential    Lavender top                  See pleural fluid
                  Protein, glucose, amylase   Red top                        profiles, p 382.
                  Gram stain, culture         Sterile
                  Cytology (if neoplasm       Cytology
                   suspected)
 Synovial fluid    Cell count, differential    Lavender top                  See synovial fluid
                  Protein, glucose            Red top                        profiles, p 389,
                  Gram stain, culture         Sterile                        and Figure 2–6.
                  Microscopic examination     Green top
                   for crystals
                  Cytology (if neoplasm       Cytology
                   [villonodular synovitis,
                   metastatic disease]
                   suspected)
 Urine            Urinalysis                                                See Table 8–24,
                   Dipstick                   Clean tube                     p 395.
                   Microscopic examination    Centrifuge tube               See Table 2–2,
                   Gram stain, culture        Sterile                        p 31.
                  Cytology (if neoplasm       Cytology                      See Figure 2–3,
                   suspected)                                                p 34.


         Staining Technique
            a. Put on gloves.
            b. Stain with crystal violet (10 seconds).
            c. Rinse with gently running water (5 seconds).
            d. Flood with Gram iodine solution (10–30 seconds).
            e. Rinse with gently running water (5 seconds).
                          Laboratory Procedures in the Clinical Setting   27

     f. Decolorize with acetone-alcohol solution until no more
        blue color leaches from the slide (5 seconds).
     g. Rinse immediately with water (5 seconds).
     h. Counterstain with safranin O (10 seconds).
     i. Rinse with water (5 seconds).
     j. Let the slide air-dry (or carefully blot with filter paper),
        then examine it under the microscope.
   Microscopic Examination
     a. Examine the smear first using the low-power lens for leuko-
        cytes and fungi. Screen for the number and color of poly-
        morphonuclear cells (cell nuclei should be pink, not blue).
     b. Examine using the high-power oil-immersion lens for
        microbial forms. Screen for intracellular organisms.
        Review the slide systematically for (1) fungi (mycelia,
        then yeast), (2) small gram-negative rods (bacteroides,
        haemophilus, etc) (3) gram-negative cocci (neisseria, etc),
        (4) gram-positive rods (listeria, etc), and (5) gram-positive
        cocci (streptococcus, staphylococcus, etc).
     c. Label positive slides with the patient’s name and
        identification number and save them for later review.
     d. Figure 2–1 illustrates typical findings on a Gram-stained
        smear of sputum.

B. Wright Stain of Peripheral Blood Smear
   Preparation of Smear
      a. Obtain a fresh specimen of blood by pricking the patient’s
         finger with a lancet. If alcohol is used to clean the finger-
         tip, wipe it off first with a gauze pad.
      b. Place a single drop of blood on a glass slide. Lay a second
         glass slide over the first one and rapidly pull it away
         lengthwise to leave a thin smear.
      c. Let the smear air-dry. Do not heat-fix.
   Staining Technique
      a. Stain with fresh Wright stain (1 minute).
      b. Gently add an equal amount of water and gently blow on the
         smear to mix the stain and water. Repeat by adding more
         water and blowing to mix. Look for formation of a shiny sur-
         face scum. Then allow the stain to set (3–4 minutes).
      c. Rinse with gently running water (5 seconds).
      d. Clean the back of the slide with an alcohol pad if necessary.
   Microscopic Examination
      a. Examine the smear first using the low-power lens to select
         a good area for study (red and white cells separated from
         one another).
28     Pocket Guide to Diagnostic Tests




     White blood cells           Red blood cells         Squamous epithelial cells




 Curschmann's spirals             Bronchial epithelial cells



Gram            Gram                 Yeast                 Acid-fast         P carinii
cocci           rods                                       bacilli

Figure 2–1. Common findings on microscopic examination of the sputum. Most elements
can be seen on Gram-stained smears except for acid-fast bacilli (auramine-rhodamine stain)
and Pneumocystis carinii (Giemsa stain). (Modified and reproduced, with permission from
Krupp MA et al: Physician’s Handbook, 21st ed. Originally published by Lange Medical Pub-
lications. Copyright © 1985 by The McGraw-Hill Companies, Inc.)


            b. Then move to the high-power oil-immersion lens. Review
               the slide systematically for (1) platelet morphology, (2)
               white cells (differential types, morphology, toxic granula-
               tions and vacuoles, etc), and (3) red cells (size, shape,
               color, stippling, nucleation, etc).
            c. Label slides with the patient’s name and identification
               number and save them for later review.
            d. See Figure 2–2 for examples of common peripheral blood
               smear abnormalities.


3. OTHER BEDSIDE LABORATORY PROCEDURES
     A. Urinalysis
        Collection and Preparation of Specimen
           a. Obtain a midstream urine specimen from the patient. The
              sample must be free of skin epithelium or bacteria, secre-
              tions, hair, lint, etc.
                               Laboratory Procedures in the Clinical Setting      29


RED BLOOD CELLS




   Normal             Target cells       Teardrop cells             Elliptocytes
   red cells                                                        (ovalocytes)




Acanthocytes          Macrocytes          Spherocytes           Stomatocytes




 Hypochromic         Schistocytes         Howell-Jolly              Basophilic
 microcytic          (schizocytes)        bodies                    stippling
 red cells



                      Echinocytes          Sickle cells              Bite cells

WHITE BLOOD CELLS




  Monocyte            Eosinophil          Lymphocyte                 Basophil




                            Neutrophil
                            (polymorphonuclear
                            leukocyte)
         Band                                       Neutrophil with
         neutrophil                                 toxic granulations

PLATELETS
                             Hypersegmented
                             neutrophil



               Figure 2–2. Common peripheral blood smear findings.
30   Pocket Guide to Diagnostic Tests

        b. Examine the specimen while fresh (still warm). Otherwise,
           bacteria may proliferate, casts and crystals may dissolve,
           and particulate matter may settle out. (Occasionally, amor-
           phous crystals precipitate out, obscuring formed elements.
           In cold urine, they are amorphous urate crystals; these may
           be dissolved by gently rewarming the urine. In alkaline
           urine, they are amorphous phosphate crystals; these may
           be dissolved by adding 1 mL of acetic acid.)
        c. Place 10 mL in a tube and centrifuge at 2000–3000 rpm for
           3–5 minutes.
        d. Discard the supernatant. Resuspend the sediment in the
           few drops that remain by gently tilting the tube.
        e. Place a drop on a glass slide, cover it with a coverslip, and
           examine under the microscope; no stain is needed. If bac-
           terial infection is present, a single drop of methylene blue
           applied to the edge of the coverslip, or a Gram-stained smear
           of an air-dried, heat-fixed specimen, can assist in distin-
           guishing gram-negative rods (eg, E coli, proteus, klebsiella)
           from gram-positive cocci (eg, enterococcus, Staphylococcus
           saprophyticus).
     Procedural Technique
        a. While the urine is being centrifuged, examine the remain-
           der of the specimen by inspection and reagent strip (“dip-
           stick”) testing.
        b. Inspect the specimen for color and clarity. Normally, urine
           is yellow or light orange. Dark orange urine is caused by
           ingestion of the urinary tract analgesic phenazopyridine
           (Pyridium, others); red urine, by hemoglobinuria,
           myoglobinuria, beets, senna, or rifampin therapy; green
           urine, by Pseudomonas infection or iodochlorhydroxyquin
           or amitriptyline therapy; brown urine, by bilirubinuria or
           fecal contamination; black urine, by intravascular hemoly-
           sis, alkaptonuria, melanoma, or methyldopa therapy; pur-
           plish urine, by porphyria; and milky white urine, by pus,
           chyluria, or amorphous crystals (urates or phosphates). Tur-
           bidity of urine is caused by pus, red blood cells, or crystals.
        c. Reagent strips provide information about specific gravity,
           pH, protein, glucose, ketones, bilirubin, heme, nitrite, and
           esterase (Table 2–2). Dip a reagent strip in the urine and
           compare it with the chart on the bottle. Follow the timing
           instructions carefully. Note: Reagent strips cannot be
           relied on to detect some proteins (eg, globulins, light
           chains) or sugars (other than glucose).
        d. Record the results.
                                 Laboratory Procedures in the Clinical Setting              31

TABLE 2–2. COMPONENTS OF THE URINE DIPSTICK.1

                            Lowest
                           Detectable
      Test    Values        Range                            Comments

 Specific     1.001–      1.000–1.030        Highly buffered alkaline urine may yield low
  gravity     1.035                          specific gravity readings. Moderate protein-
                                             uria (100–750 mg/dL) may yield high read-
                                             ings. Loss of concentrating or diluting
                                             capacity indicates renal dysfunction.
 pH          5–9 units   5–8.5 units        Excessive urine on strip may cause protein
                                             reagent to run over onto pH area, yielding
                                             falsely low pH reading.
 Protein     O           15–30 mg/dL        False-positive readings can be caused by
                          albumin            highly buffered alkaline urine. Reagent more
                                             sensitive to albumin than other proteins.
                                             A negative result does not rule out the pres-
                                             ence of globulins, hemoglobin, Bence Jones
                                             proteins, or mucoprotein.
                                                1+ = 30 mg/dL       3+ = 300 mg/dL
                                                2+ = 100 mg/dL 4+ = ≥ 2000 mg/dL
 Glucose     O           75–125 mg/dL       Test is specific for glucose. False-negative
                                             results occur with urinary ascorbic acid con-
                                             centrations ≥ 50 mg/dL and with ketone body
                                             levels ≥ 50 mg/dL Test reagent reactivity also
                                             varies with specific gravity and temperature.
                                                Trace = 100 mg/dL 1 = 1000 mg/dL
                                                1⁄4 = 250 mg/dL       2 = ≥ 2000 mg/dL
                                                1⁄2 = 500 mg/dL
 Ketone      O           5–10 mg/dL         Test does not react with acetone or b-hydroxy-
                          acetoacetate       butyric acid. (Trace) false-positive results
                                             may occur with highly pigmented urines
                                             or those containing levodopa metabolites
                                             or sulfhydryl-containing compounds
                                             (eg, mesna).
                                             Trace = 5 mg/dL        Moderate = 40 mg/dL
                                             Small = 15 mg/dL Large = 80–160 mg/dL
 Bilirubin   O           0.4–0.8 mg/dL      Indicates hepatitis (conjugated bilirubin).
                                             False-negative readings can be caused by
                                             ascorbic acid concentrations ≥ 25 mg/dL.
                                             False-positive readings can be caused by
                                             etodolac metabolites. Test is less sensitive
                                             than Ictotest Reagent tablets.

                                                                                 (continued )
32         Pocket Guide to Diagnostic Tests

TABLE 2–2 (CONT’D). COMPONENTS OF THE URINE DIPSTICK.1

                                     Lowest
                                    Detectable
     Test            Values          Range                              Comments

 Blood              O2            0.015–              Test equally sensitive to myoglobin and hemo-
                                   0.062 mg/dL         globin (including both intact erythrocytes and
                                   hemoglobin          free hemoglobin). False-positive results can be
                                                       caused by oxidizing contaminants (hypo-
                                                       chlorite) and microbial peroxidase (urinary
                                                       tract infection). Test sensitivity is reduced in
                                                       urines with high specific gravity, captopril, or
                                                       heavy proteinuria.
 Nitrite            O             0.06–0.1 mg/dL      Test depends on the conversion of nitrate
                                   nitrite ion         (derived from the diet) to nitrite by gram-
                                                       negative bacteria in urine. Test specific for
                                                       nitrite. False-negative readings can be caused
                                                       by ascorbic acid. Test sensitivity is reduced in
                                                       urines with high specific gravity.
 Leukocytes         O3            6–15 WBCs/hpf       Indicator of urinary tract infection. Test detects
  (esterase)                                           esterases contained in granulocytic leukocytes.
                                                       Test sensitivity is reduced in urines with high
                                                       specific gravity, elevated glucose concentra-
                                                       tions (≥ 4 g/dL), or presence of cephalexin,
                                                       cephalothin, tetracycline, or high concentra-
                                                       tions of oxalate.

1 Package    insert, revised 9/95. Bayer Diagnostics Reagent Strips for Urinalysis, Bayer Corporation.
2 Except   in menstruating females.
3 Except   in females with vaginitis.


           Microscopic Examination
             a. Examine the area under the coverslip under the low-power
                and high-dry lenses for cells, casts, crystals, and bacteria. (If
                a Gram stain is done, examine under the oil immersion lens.)
             b. Cells may be red cells, white cells, squamous cells, transi-
                tional (bladder) epithelial cells, or atypical (tumor) cells. Red
                cells suggest upper or lower urinary tract infections (cysti-
                tis, prostatitis, pyelonephritis), glomerulonephritis, collagen
                vascular disease, trauma, renal calculi, tumors, drug reac-
                tions, and structural abnormalities (polycystic kidneys).
                White cells suggest inflammatory processes such as urinary
                tract infection (most common), collagen vascular disease, or
                interstitial nephritis. Red cell casts are considered patho-
                gnomonic of glomerulonephritis; white cell casts, of pyelo-
                nephritis; and fatty (lipid) casts, of nephrotic syndrome.
                          Laboratory Procedures in the Clinical Setting   33

       c. The finding on a Gram-stained smear of unspun, clean,
          fresh urine of even one bacterium per field under the oil-
          immersion lens correlates fairly well with bacterial culture
          colony counts of greater than 100,000 organisms per µL.
       d. See Table 8–24, p 395, for a guide to interpretation of urin-
          alysis; and Figure 2–3 for a guide to microscopic findings
          in urine.
B. Vaginal Fluid Wet Preparation
   Preparation of Smear and Staining Technique
      a. Place a small amount of vaginal discharge on a glass slide.
      b. Add 2 drops of sterile saline solution.
      c. Place a coverslip over the area to be examined.
   Microscopic Examination
      a. Examine under the microscope, using the high-dry lens
         and a low light source.
      b. Look for motile trichomonads (undulating protozoa pro-
         pelled by four flagella). Look for clue cells (vaginal epithe-
         lial cells with large numbers of organisms attached to
         them, obscuring cell borders), pathognomonic of Gard-
         nerella vaginalis-associated vaginosis.
      c. See Figure 2–4 for an example of a positive wet prep (tricho-
         monads, clue cells) and Table 8–25, p 397 for the dif-
         ferential diagnosis of vaginal discharge.
C. Skin or Vaginal Fluid KOH Preparation
   Preparation of Smear and Staining Technique
      a. Obtain a skin specimen by using a No. 15 scalpel blade to
         scrape scales from the skin lesion onto a glass slide or to
         remove the top of a vesicle onto the slide. Or place a sin-
         gle drop of vaginal discharge on the slide.
      b. Place 1 or 2 drops of potassium hydroxide (10–20%) on
         top of the specimen on the slide. Lay a coverslip over the
         area to be examined.
      c. Heat the slide from beneath with a match or Bunsen burner
         flame until the slide contents begin to bubble.
      d. Clean carbon off the back side of the slide with an alcohol
         pad if necessary.
      Note: A fishy amine odor upon addition of KOH to a vaginal
      discharge is typical of bacterial vaginosis caused by Gard-
      nerella vaginalis.
   Microscopic Examination
      a. Examine the smear under the high-dry lens for mycelial
         forms. Branched, septate hyphae are typical of derma-
         tophytosis (eg, trichophyton, epidermophyton, microspo-
34    Pocket Guide to Diagnostic Tests


             Amorphous phosphates



                                                                 Amorphous
                               Calcium                           urates
                              carbonate
                                crystals
                                             Uric acid crystals


                               Mucus
                                                    Epithelial
                               threads
                                                      cells


                         Cylindroid

          Triple                              Waxy                    Calcium
                                              cast                    oxalate
      phosphate
        crystals              Bacteria                                crystals
                                                         Fatty
                                                         cast
                                        White
                                       cells and
                     Granular          white cell
                     cast                casts
                    Hyaline                                       Fat
                     cast                                         droplets
     Calcium
     phosphate
     crystals
                                                    Epithelial
                                                    cell cast
                    Red                                   Sodium
                    blood cells               Spermatozoa urate crystals


                                                           Cystine crystals

                                            Tyrosine
           Ammonium                         needles
           urate crystals                                  Leucine spheres
         ALKALINE REACTION                           ACID REACTION

Figure 2–3. Microscopic findings on examination of the urine. (Modified and reproduced,
with permission from Krupp MA et al: Physician’s Handbook, 21st ed. Originally published
by Lange Medical Publications. Copyright © 1985 by The McGraw-Hill Companies, Inc.)
                                   Laboratory Procedures in the Clinical Setting     35

                         Trichomonad




                                     White
                                     blood
                                     cells

                             Clue cell




                      Normal
                      epithelial
                      cell



                                               White blood
                                                   cell


Figure 2–4. Wet preparation showing trichomonads, white blood cells, and “clue” cells.

             rum species); branched, septate pseudohyphae with or
             without budding yeast forms are seen with candidiasis
             (candida species); and short, curved hyphae plus clumps of
             spores (“spaghetti and meatballs”) are seen with tinea ver-
             sicolor (Malassezia furfur).
          b. See Figure 2–5 for an example of a positive KOH prep.
 D. Synovial Fluid Examination for Crystals
    Preparation of Smear
       a. No stain is necessary.
       b. Place a small amount of synovial fluid on a glass slide.
       c. Place a coverslip over the area to be examined.
    Microscopic Examination
       a. Examine under a polarized light microscope with a red
          compensator, using the high-dry lens and a moderately
          bright light source.
36     Pocket Guide to Diagnostic Tests




                                    Pseudohyphae




                                                    Budding
                                                    yeast




Figure 2–5. KOH preparation showing mycelial forms (pseudohyphae) and budding yeast typ-
ical of Candida albicans.




           b. Look for needle-shaped, negatively birefringent urate crys-
              tals (crystals parallel to the axis of the compensator appear
              yellow) in gout or rhomboidal, positively birefringent cal-
              cium pyrophosphate crystals (crystals parallel to the axis of
              the compensator appear blue) in pseudogout.
           c. See Figure 2–6 for examples of positive synovial fluid
              examinations for these two types of crystals.

     E. Pulse Oximetry
        Indications
           To measure oxygen saturation in a noninvasive and often con-
           tinuous fashion.
                                    Laboratory Procedures in the Clinical Setting        37




                   Gout                                      Pseudogout

Figure 2–6. Examination of synovial fluid for crystals, using a compensated, polarized micro-
scope. In gout, crystals are needle-shaped, negatively birefringent, and composed of
monosodium urate. In pseudogout, crystals are rhomboidal, positively birefringent, and
composed of calcium pyrophosphate dihydrate. In both diseases, crystals can be found free-
floating or within polymorphonuclear cells.


        Contraindications
           a. Hypotension, hypothermia, low perfusion states, severe
              or rapid desaturation, and severe anemia (hemoglobin
              < 5 g/dL) cause inaccurate readings.
           b. Hyperbilirubinemia, methemoglobinemia, fetal hemoglob-
              inemia, and carboxyhemoglobinemia can falsely elevate
              oxygen saturation measurements.
           c. Excessive ambient light, simultaneous use of a blood pres-
              sure cuff, the presence of intravascular dyes (eg, methyl-
              ene blue), and electrical interference (eg, MRI scanners,
              electrosurgery) can also cause erroneous readings.
        Approach to the Patient
           The patient should be positioned close to the pulse oximeter
           and should hold the probe site still. The sampling area should
           have good circulation and be free of skin irritation.
        Procedural Technique
           a. Plug the pulse oximeter into a grounded AC power outlet
              or make sure that sufficient battery power is available.
              Turn the oximeter on and wait until self-calibration is
              complete.
38   Pocket Guide to Diagnostic Tests

         b. Select the probe to be used and connect it to the pulse
            oximeter. The probe consists of a light source (a red light-
            emitting device [LED] in most cases) and a photodetector.
            Probes are available for the ear, finger, and, in neonates,
            the foot, ankle, palm, calf, and forearm.
         c. Attach the probe to the patient after cleansing the sur-
            rounding skin with an alcohol swab. Some probes come
            with double-sided adhesive disks that improve probe sig-
            nal.
         d. Watch the waveform and pulse indicators to assess the
            quality of the signal. Readjust if a poor signal is present.
         e. Set alarm warnings on the device.
         f. Check the probe site at least every 4 hours. Care should be
            taken not to apply tension to the probe cables.
      Possible Complications
        Allergic reaction to adhesives.
      Comments
        Because of the curvilinear nature of the oxygen-hemoglobin
        dissociation curve, oxygen saturation (SaO2) is not directly pro-
        portionate to oxygen partial pressure (PaO2). Therefore, a rela-
        tively small change in oxygen saturation (eg, from 94% to 83%)
        can represent a large change in PaO2 (eg, from 80 mm Hg to 50
        mm Hg). In addition, the dissociation curve varies markedly
        from patient to patient and with pH, temperature, and altitude.
        To ensure accurate assessment of oxygenation, one should cor-
        relate pulse oximetry with arterial blood gas analysis.


REFERENCES
Gram Stain
Fournier AM: The Gram stain. Ann Intern Med 1998;128:776.
Hirschmann JV: The sputum Gram stain. J Gen Intern Med 1991;6:261.
Popescu A, Doyle RJ: The Gram stain after more than a century.
     Biotech Histochem 1996;71:145.
Reed WW et al: Sputum gram’s stain in community-acquired pneumo-
     coccal pneumonia. A meta-analysis. West J Med 1996;165:197.

Urinalysis
Jou WW, Powers RD: Utility of dipstick urinalysis as a guide to man-
     agement of adults with suspected infection or hematuria. South
     Med J 1998;91:266.
Lorincz AE et al: Urinalysis: current status and prospects for the future.
     Ann Clin Lab Sci 1999;29:169.
                            Laboratory Procedures in the Clinical Setting   39

Misdraji J, Nguyen PL: Urinalysis. When—and when not—to order.
    Postgrad Med 1996;100:173.
Semeniuk H et al: Evaluation of the leukocyte esterase and nitrite urine
    dipstick screening tests for detection of bacteriuria in women with
    suspected uncomplicated urinary tract infections. J Clin Microbiol
    1999;37:3051.

Vaginal Wet Prep
Ferris DG et al: Office laboratory diagnosis of vaginitis. Clinician-
     performed tests compared with a rapid nucleic acid hybridization
     test. J Fam Pract 1995;41:575.
Thihnkhamrop J: Vaginal fluid pH as a screening test for vaginitis. Int
     J Gynaecol Obstet 1999;66:143.
Wiesenfeld HC et al: The infrequent use of office-based diagnostic tests
     for vaginitis. Am J Obstet Gynecol 1999;181:39.

Synovial Fluid Examination
Schumacher HR: Crystal-induced arthritis: an overview. Am J Med
    1996;100:46S.

Pulse Oximetry
Franklin ML: Transcutaneous measurement of partial pressure of oxy-
     gen and carbon dioxide. Respir Care Clin North Am 1995;1:11.
Grap MJ: Pulse oximetry. Crit Care Nurs 1998;18:94.
Jensen LA, Onyskiw JE, Prasad NG: Meta-analysis of arterial oxygen
     saturation monitoring by pulse oximetry in adults. Heart Lung
     1998;27:387.
Ortiz FO et al: Accuracy of pulse oximetry in sickle cell disease. Am J
     Respir Crit Care Med 1999;159:447.
Sinex JE: Pulse oximetry: principles and limitations. Am J Emerg Med
     1999;17:59.
Smatlak P et al: Clinical evaluation of noninvasive monitoring of oxygen
     saturation in critically ill patients. Am J Crit Care 1998;7:370.
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                                                                            3
                          Common Laboratory Tests:
                         Selection and Interpretation




                      Diana Nicoll, MD, PhD, MPA, Stephen J. McPhee, MD,
                                           and Michael Pignone, MD, MPH




        HOW TO USE THIS SECTION

        This section contains information about commonly used laboratory
        tests. It includes most of the blood, urine, and cerebrospinal fluid tests
        found in this book, with the exception of drug levels. Entries are in out-
        line format and are arranged alphabetically.

        Test/Reference Range/Collection
        This first outline listing begins with the common test name, the speci-
        men analyzed, and any test name abbreviation (in parentheses).
             Below this in the first outline listing is the reference range for
        each test. The first entry is in conventional units, and the second entry
        (in [brackets]) is in SI units (Système International d’Unités). Any
        panic values for a particular test are placed here after the word
        “Panic.” The reference ranges provided are from several large med-
        ical centers; consult your own clinical laboratory for those used in
        your institution.
                                           41
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
42   Pocket Guide to Diagnostic Tests

     This outline listing also shows which tube to use for collecting
blood and other body fluids, how much the test costs (in relative sym-
bolism; see below), and how to collect the specimen. Listed below are
the common collection tubes and their contents:

             Tube Top Color Tube Contents            Typically Used In

             Lavender        EDTA                    Complete blood count
             Marbled         Serum separator         Serum chemistry tests
             Red             None                    Blood banking (serum)
             Blue            Citrate                 Coagulation studies
             Green           Heparin                 Plasma studies
             Yellow          Acid citrate            HLA typing
             Navy            Trace metal free        Trace metals (eg, lead)
             Gray            Inhibitor of glycolysis Lactic acid
                                (sodium fluoride)



The scale used for the cost of each test is:

                          Approximate Symbol Used
                             Cost       in Tables

                           $1–20            $
                           $21–50           $$
                           $51–100          $$$
                           > $100           $$$$



Physiologic Basis
This outline listing contains physiologic information about the substance
being tested. Information on classification and biologic importance, as
well as interactions with other biologic substances and processes, is
included.

Interpretation
This outline lists clinical conditions that affect the substance being
tested. Generally, conditions with higher prevalence will be listed first.
When the sensitivity of the test for a particular disease is known, that
                    Common Laboratory Tests: Selection and Interpretation   43

information will follow the disease name in parentheses, eg, “rheuma-
toid arthritis (83%).” Some of the common drugs that can affect the test
substance in vivo will also be included in this outline listing.

Comments
This outline listing sets forth general information pertinent to the use
and interpretation of the test and important in vitro interferences with
the test procedure. Appropriate general references are also listed.

Test Name
The test name is placed as a header to the rest of the outline list to allow
for quick referencing.
                                                                                                                                                                      44
Test /Range/Collection           Physiologic Basis                         Interpretation                                 Comments
ABO grouping, serum The four blood groups A, B, O, and         In the US white population, 45% are    For both blood donors and recipients,




                                                                                                                                                                      Pocket Guide to Diagnostic Tests
  and red cells         AB are determined by the presence       type O, 40% A, 11% B, 4% AB.           routine ABO grouping includes both
(ABO)                   of antigens A and B or their absence   In the African-American population,     red cell and serum testing, as checks
                        (O) on a patient’s red blood cells.     49% are type O, 27% A, 20% B,          on each other.
Red                    Antibodies are present in serum for      4% AB.                                Tube testing is as follows: patient’s red




                                                                                                                                                      ABO Grouping
$                       which red cells lack antigen.          In the US Asian population, 40% are     cells are tested with anti-A and anti-B
Properly identified and                                          type O, 28% A, 27% B, 5% AB.           for the presence or absence of agglu-
  labeled blood speci-                                         In the Native American population, 79% tination (forward or cell grouping),
  mens are critical.                                            are type O, 16% A, 4% B, <1% AB.       and patient’s serum is tested against
                                                                                                       known A and B cells (reverse or
                                                                                                       serum grouping).
                                                                                                      Technical Manual of the American
                                                                                                       Association of Blood Banks, 11th ed.
                                                                                                       American Association of Blood
                                                                                                       Banks, 1993.
Acetaminophen, serum In overdose, liver and renal toxicity     Increased in: Acetaminophen over-           Do not delay acetylcysteine
(Tylenol; others)     are produced by the hydroxylated          dose. Interpretation of serum aceta-        (Mucomyst) treatment (140 mg/kg
                      metabolite if it is not conjugated        minophen level depends on time since        orally) if stat levels are unavailable.
10–20 mg/L            with glutathione in the liver.            ingestion. Levels drawn <4 hours after     Lancet 1971;1:519.
[66–132 µmol/L]                                                 ingestion cannot be interpreted since      Pediatrics 1975;55:871.
Panic: >50 mg/L




                                                                                                                                                      Acetaminophen
                                                                the drug is still in the absorption and    Lancet 1976;2:109.
                                                                distribution phase. Use nomogram
Marbled                                                         (Figure 8–1, p 336) to evaluate possible
$$                                                              toxicity. Levels >150 mg/dL at 4 hours
For suspected overdose,                                         or >50 mg/dL at 12 hours after inges-
 draw two samples at                                            tion suggest toxicity. Nomogram
 least 4 hours apart, at                                        inaccurate for chronic ingestions.
 least 4 hours after
 ingestion. Note time
 of ingestion, if known.
 Order test stat.
Acetoacetate, serum    Acetoacetate, acetone, and β-hydroxy- Present in: Diabetic ketoacidosis, alco-   Nitroprusside test is semiquantitative;
 or urine               butyrate contribute to ketoacidosis   holic ketoacidosis, prolonged fasting,     it detects acetoacetate and is sensitive
                        when oxidative hepatic metabolism     severe carbohydrate restriction with       down to 5–10 mg/dL.
0 mg/dL [µmol/L]        of fatty acids is impaired.           normal fat intake.                        Trace = 5 mg/dL, small = 15 mg/dL,
                       Proportions in serum vary but are                                                 moderate = 40 mg/dL, large =
Marbled or urine        generally 20% acetoacetate, 78%                                                  80 mg/dL [1 mg/dL = 100 µmol/L].
  container             β-hydroxybutyrate, and 2% acetone.                                              β-Hydroxybutyrate is not a ketone and




                                                                                                                                                    Acetoacetate
$                                                                                                        is not detected by the nitroprusside
Urine sample should                                                                                      test. Acetone is also not reliably




                                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
  be fresh.                                                                                              detected by this method.
                                                                                                        Failure of test to detect β-hydroxy-
                                                                                                         butyrate in ketoacidosis may produce
                                                                                                         a seemingly paradoxical increase in
                                                                                                         ketones with clinical improvement as
                                                                                                         nondetectable β-hydroxybutyrate is
                                                                                                         replaced by detectable acetoacetate.
                                                                                                        Br Med J 1972;2:565.
Acetylcholine recep-   Acetylcholine receptor antibodies are Positive in: Myasthenia gravis.            Titer has been found to correlate with




                                                                                                                                                    Acetylcholine receptor antibody
 tor antibody, serum    involved in the pathogenesis of      Sensitivity = 73%.                          clinical severity.
                        myasthenia gravis. Sensitive radio- Single fiber EMG may have best               J Neurol Neurosurg Psychiatry
Negative                assay or ELISA is available based on sensitivity.                                1993;56:496.
                        inhibition of binding of 125I alpha-                                            Clin Chem 1993;39:2053.
Marbled                 bungarotoxin to the acetylcholine                                               Muscle Nerve 1992;15:720.
$$                      receptor.




                                                                                                                                                                                      45
                                                                                                                                                                                      46
Test /Range/Collection              Physiologic Basis                          Interpretation                               Comments
Adrenocorticotropic       Pituitary ACTH (release stimulated by Increased in: Pituitary (40–200 pg/mL) ACTH levels (RIA) can only be inter-




                                                                                                                                                                                      Pocket Guide to Diagnostic Tests
 hormone, plasma           hypothalamic corticotropin-releasing and ectopic (200–71,000 pg/mL) Cush- preted when measured with cortisol
(ACTH)                     factor) stimulates cortisol release   ing’s syndrome, primary adrenal insuf- after standardized stimulation or sup-
                           from the adrenal gland. There is      ficiency (>250 pg/mL), adrenogenital    pression tests (see Adrenocortical




                                                                                                                                                        Adrenocorticotropic hormone
20–100 pg/mL               feedback regulation of the system     syndrome with impaired cortisol        insufficiency algorithm, p 338, and
[4–22 pmol/L]              by cortisol.                          production.                            Cushing’s syndrome algorithm, p 340).
                          ACTH is secreted episodically and     Decreased in: Adrenal Cushing’s syn- Postgrad Med 1998;104:61.
Heparinized plastic        shows circadian variation, with       drome (<20 pg/mL), pituitary ACTH
 container                 highest levels at 6:00–8:00 AM;       (secondary adrenal) insufficiency
$$$$                       lowest levels at 9:00–10:00 PM.       (<50 pg/mL).
Send promptly to labo-
 ratory on ice. ACTH
 is unstable in plasma,
 is inactivated at room
 temperature, and
 adheres strongly to
 glass. Avoid all
 contact with glass.
Alanine aminotrans-       Intracellular enzyme involved in        Increased in: Acute viral hepatitis (ALT     ALT is the preferred enzyme for evalu-




                                                                                                                                                        Alanine aminotransferase
 ferase, serum             amino acid metabolism. Present in       > AST), biliary tract obstruction            ation of liver injury.
(ALT, SGPT, GPT)           large concentrations in liver, kidney; (cholangitis, choledocholithiasis), alco-    Screening ALT in low-risk populations
                           in smaller amounts, in skeletal mus-    holic hepatitis and cirrhosis (AST >         has a low (12%) positive predictive
0–35 U/L                   cle and heart. Released with tissue     ALT), liver abscess, metastatic or pri-      value.
[0–0.58 µkat/L]            damage, particularly liver injury.      mary liver cancer; right heart failure,     Compr Ther 1994;20:50.
(laboratory-specific)                                               ischemia or hypoxia, injury to liver        Hosp Pract (Off Ed) Nov 1994;29:32.
                                                                   (“shock liver”), extensive trauma. Drugs    Dig Dis Sci 1993;38:2145.
Marbled                                                            that cause cholestasis or hepatotoxicity.
$                                                                 Decreased in: Pyridoxine (vitamin B6)
                                                                   deficiency.
Albumin, serum   Major component of plasma proteins; Increased in: Dehydration, shock,            Serum albumin gives an indication of
                  influenced by nutritional state,        hemoconcentration.                        severity in chronic liver disease.
3.4–4.7 g/dL      hepatic function, renal function, and Decreased in: Decreased hepatic syn-      Useful in nutritional assessment if
[34–47 g/L]       various diseases. Major binding pro- thesis (chronic liver disease, malnutri-    there is no impairment in production
                  tein. While there are more than        tion, malabsorption, malignancy,          or increased loss of albumin and is an
Marbled           50 different genetic variants (allo-   congenital analbuminemia [rare]).         independent risk factor for all-cause
                                                                                                   mortality in the elderly (age >70).




                                                                                                                                            Albumin
$                 albumins), only occasionally does a    Increased losses (nephrotic syndrome,
                  mutation cause abnormal binding        burns, trauma, hemorrhage with fluid      There is a 10% reduction in serum
                  (eg, in familial dysalbuminemic        replacement, fistulas, enteropathy,        albumin level in late pregnancy




                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
                  hyperthyroxinemia).                    acute or chronic glomerulonephritis).     (related to hemodilution).
                                                         Hemodilution (pregnancy, CHF).           J Med Genet 1994;31:355.
                                                         Drugs: estrogens.                        Proc Natl Acad Sci U S A
                                                                                                   1994;91:6476.
                                                                                                  JAMA 1994;272:1036.
                                                                                                  JAGS 1993;41:545.




                                                                                                                                                      47
                                                                                                                                                                  48
Test /Range/Collection          Physiologic Basis                      Interpretation                          Comments
Aldosterone, plasma   Aldosterone is the major mineralocor- Increased in: Primary hyper-         Testing for hyperaldosteronism and




                                                                                                                                                                  Pocket Guide to Diagnostic Tests
                       ticoid hormone and is a major regu-   aldosteronism (72%).                 hypoaldosteronism must be done
Salt-loaded            lator of extracellular volume and    Decreased in: Primary or secondary    using specific protocols, and results
 (120 meq Na+/d):      serum potassium concentration.        hypoaldosteronism.                   must be interpreted based on refer-
Supine: 3–10          For evaluation of hyperaldosteronism                                        ence values from the laboratory
Upright: 5–30 ng /dL   (associated with hypertension and                                          performing the test.
                       hypokalemia), patients should be                                          24-hour urinary excretion of aldos-
Salt-depleted          salt-loaded and recumbent when                                             terone is the most sensitive test for




                                                                                                                                            Aldosterone, plasma
 (10 meq Na+/d):       specimen is drawn.                                                         hyperaldosteronism. (See
Supine: 12–36         For evaluation of hypoaldosteronism                                         Aldosterone, urine, below.)
Upright: 17–137 ng/dL (associated with hyperkalemia),                                            The significance of an elevated plasma
[1 ng/dL =             patients should be salt-depleted and                                       aldosterone level is difficult to inter-
 27.7 pmol/L]          upright when specimen is drawn.                                            pret without simultaneous determina-
                                                                                                  tion of plasma renin activity (PRA).
Lavender or green                                                                                 In primary aldosteronism, plasma
$$$$                                                                                              aldosterone is usually elevated while
Early AM fasting speci-                                                                           PRA is low; in secondary hyperaldo-
 men. Separate imme-                                                                              steronism, both plasma aldosterone
 diately and freeze.                                                                              and PRA are usually elevated.
                                                                                                 Am J Med 1983;74:641.
                                                                                                 Med Clin North Am 1988;72:1117.
                                                                                                 Mayo Clin Proc 1990;65:96.
Aldosterone, urine*     Secretion of aldosterone is controlled Increased in: Primary and secondary     Urinary aldosterone is the most sensi-
                         by the renin-angiotensin system.       hyperaldosteronism, some patients with tive test for primary hyperaldosteron-
Salt-loaded (120 meq     Renin (synthesized and stored in       essential hypertension.                 ism. Levels >14 µg/24 h after 3 days
 Na+/d for 3–4 days):    juxtaglomerular cells of kidney)      Decreased in: Primary hypo-              of salt-loading have a 96% sensitivity
 1.5–12.5 µg/24 h        is released in response to both        aldosteronism (eg, 18-hydroxylase defi- and 93% specificity for primary
                         decreased perfusion pressure at the    ciency), secondary hypoaldosteronism    hyperaldosteronism. Only 7% of
Salt-depleted (20 meq    juxtaglomerular apparatus and nega- (hyporeninemic hypoaldosteronism).         patients with essential hypertension
 Na+/d for 3–4 days):    tive sodium balance. Renin then                                                have urinary aldosterone levels >14
 18–85 µg/24 h           hydrolyses angiotensinogen to                                                  µg/24 h after salt-loading.




                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
                                                                                                                                                 Aldosterone, urine
[1 µg/24 h = 2.77        angiotensin I, which is converted to                                          Neither serum potassium nor plasma
 nmol/d]                 angiotensin II, which then stimulates                                          renin activity (PRA) is a satisfactory
                         the adrenal gland to produce                                                   screening test for hyperaldosteron-
Bottle containing boric aldosterone.                                                                    ism. Hypokalemia is present in only
 acid                                                                                                   73% of patients with hyperaldoste-
$$$$                                                                                                    ronism on a normal sodium diet, and
                                                                                                        in 86% after salt loading. Suppressed
                                                                                                        PRA has only a 64% sensitivity and
                                                                                                        83% specificity for hyper-
                                                                                                        aldosteronism.
                                                                                                       Am J Med 1983;74:641.
                                                                                                       Med Clin North Am 1988;72:1117.
                                                                                                       Mayo Clin Proc 1990;65:96.
                                                                                                       Endocrinol Metab Clin North Am
                                                                                                        1994;23:271.
* To evaluate hyperaldosteronism, patient is salt-loaded and recumbent. Obtain 24-hour urine for aldosterone (and sodium to check that sodium
 excretion is >250 meq/day). To evaluate hypoaldosteronism, patient is salt-depleted and upright; check patient for hypotension before 24-hour
 urine collected.




                                                                                                                                                                      49
                                                                                                                                                                            50
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Alkaline phosphatase, Alkaline phosphatases are found in        Increased in: Obstructive hepatobiliary Alkaline phosphatase performs well in




                                                                                                                                                                            Pocket Guide to Diagnostic Tests
 serum                 liver, bone, intestine, and placenta.     disease, bone disease (physiologic bone measuring the extent of bone metas-
                                                                 growth, Paget’s disease, osteomalacia,   tases in prostate cancer.
41–133 IU/L                                                      osteogenic sarcoma, bone metastases), Normal in osteoporosis.




                                                                                                                                                    Alkaline phosphatasee
[0.7–2.2 µkat/L]                                                 hyperparathyroidism, rickets, benign    Alkaline phosphatase isoenzyme sepa-
 (method- and age-                                               familial hyperphosphatasemia, preg-      ration by electrophoresis or differen-
 dependent)                                                      nancy (third trimester), GI disease      tial heat inactivation is unreliable.
                                                                 (perforated ulcer or bowel infarct),     Use γ-glutamyl transpeptidase
Marbled                                                          hepatotoxic drugs.                       (GGT), which increases in hepatobil-
$                                                               Decreased in: Hypophosphatasia.           iary disease but not in bone disease,
                                                                                                          to infer origin of increased alkaline
                                                                                                          phosphatase (ie, liver or bone).
                                                                                                         Endocrinol Metab Clin North Am
                                                                                                          1990;19:1.
                                                                                                         Int J Urol 1997;4:572.
Amebic serology,         Test for presence of Entamoeba his-    Increased in: Current or past infection In some endemic areas, as many as




                                                                                                                                                    Amebic serology
 serum                    tolytica by detection of antibodies    with E histolytica. Amebic abscess        44% of those tested have positive
                          which develop 2–4 weeks after          (91%), amebic dysentery (84%),            serologies.
<1 64 titer               infection.                             asymptomatic cyst carriers (9%),         Precipitin or indirect hemagglutination
                         Tissue invasion by the organism may     patients with other diseases and healthy (IHA) and recombinant antigen-based
Marbled                   be necessary for antibody production. people (2%).                               ELISA tests are available.
$$                                                                                                        N Engl J Med 1978;298:262.
                                                                                                          Ann Trop Parasitol 1993;87:31.
Ammonia, plasma       Ammonia is liberated by bacteria in       Increased in: Liver failure, hepatic        Correlates poorly with degree of he-
 (NH3)                 the large intestine or by protein         encephalopathy (especially if protein       patic encephalopathy. Test not useful
18–60 µg/dL            metabolism and is rapidly converted consumption is high or if there is GI             in adults with known liver disease.
[11–35 µmol/L]         to urea in liver.                         bleeding), fulminant hepatic failure,      Test is not as useful as CSF glutamine
                      In liver disease or portal-systemic        Reye’s syndrome, portacaval shunting,       (see p 97).
Green                  shunting, the blood ammonia               cirrhosis, urea cycle metabolic defects,   Klin Wochenschr 1990;68:175.
$$                     concentration increases.                  urea-splitting urinary tract infection     Baillieres Clin Gastroenterol
Separate plasma from In acute liver failure, elevation of blood with urinary diversion, and organic          1992;6:609.
 cells immediately.    ammonia may cause brain edema; in         acidemias. Drugs: diuretics, acetazol-     Proc Soc Exp Biol Med 1994;206:329.




                                                                                                                                                     Ammonia

                                                                                                                                                               Common Laboratory Tests: Selection and Interpretation
 Avoid hemolysis.      chronic liver failure, it may be          amide, asparaginase, fluorouracil
 Analyze immediately. responsible for hepatic                    (5-FU) (transient), others.
 Place on ice.         encephalopathy.                          Spuriously increased by any ammonia-
                                                                 containing detergent on laboratory
                                                                 glassware.
                                                                Decreased in: Decreased production by
                                                                 gut bacteria (kanamycin, neomycin).
                                                                 Decreased gut absorption (lactulose).




                                                                                                                                                               51
                                                                                                                                                                                           52
Test /Range/Collection             Physiologic Basis                          Interpretation                                Comments
Amylase, serum           Amylase hydrolyzes complex              Increased in: Acute pancreatitis             Macroamylasemia is indicated by high




                                                                                                                                                                                           Pocket Guide to Diagnostic Tests
                          carbohydrates.                          (70–95%), pancreatic pseudocyst, pan-        serum but low urine amylase.
20–110 U/L               Serum amylase is derived primarily       creatic duct obstruction (cholecystitis,    Serum lipase is an alternative test for
[0.33–1.83 µkat/L]        from pancreas and salivary glands       choledocholithiasis, pancreatic carci-       acute pancreatitis.
 (laboratory-specific)     and is increased with inflammation       noma, stone, stricture, duct sphincter      Amylase isoenzymes are not of practi-
                          or obstruction of these glands.         spasm), bowel obstruction and infarc-        cal use because of technical problems.




                                                                                                                                                           Amylase
Marbled                  Other tissues have some amylase          tion, mumps, parotitis, diabetic keto-      Gastroenterol Clin North Am
$                         activity, including ovaries, small and acidosis, penetrating peptic ulcer,           1990;19:793.
                          large intestine, and skeletal muscle.   peritonitis, ruptured ectopic pregnancy,    J Gastroenterol 1994;29:189.
                                                                  macroamylasemia. Drugs: azathioprine,       Gastroenterologist 1994;2:119.
                                                                  hydrochlorothiazide.                        Pancreas 1998;16:45.
                                                                 Decreased in: Pancreatic insufficiency,
                                                                  cystic fibrosis. Usually normal or low
                                                                  in chronic pancreatitis.
Angiotensin-             ACE is a dipeptidyl carboxypeptidase Increased in: Sarcoidosis (sensitivity          Test is not useful as a screening test for




                                                                                                                                                           Angiotensin-converting enzyme
 converting enzyme,       that converts angiotensin I to the     = 63%, specificity = 93%, LRT = 9.0)           sarcoidosis (low sensitivity).
 serum                    vasopressor, angiotensin II.           (when upper limit of normal is 50),          Specificity is compromised by positive
(ACE)                    ACE is normally present in the kid-     hyperthyroidism, acute hepatitis, pri-        tests in diseases more common than
                          neys and other peripheral tissues. In  mary biliary cirrhosis, diabetes mellitus,    sarcoidosis.
12–35 U/L                 granulomatous disease, ACE levels      multiple myeloma, osteoarthritis, amy-       Some advocate measurement of ACE to
[<590 nkat/L]             increase, derived from epithelioid     loidosis, Gaucher’s disease, pneumo-          follow disease activity in sarcoidosis.
 (method-dependent)       cells within granulomas.               coniosis, histoplasmosis, miliary            J Clin Pathol 1983;36:938.
                                                                 tuberculosis. Drugs: dexamethasone.
Marbled                                                         Decreased in: Renal disease, obstructive
$$                                                               pulmonary disease, hypothyroidism.
Antibody screen,       Detects antibodies to non-ABO red        Positive in: Presence of alloantibody,   In practice, a type and screen (ABO
 serum                  blood cell antigens in recipient’s       autoantibody.                            and Rh grouping and antibody
                        serum, using reagent red cells                                                    screen) is adequate workup for
Red                     selected to possess antigens against                                              patients undergoing operative proce-




                                                                                                                                                   Antibody screen
$                       which common antibodies can be                                                    dures unlikely to require transfusion.
Properly identified and produced.                                                                         A negative antibody screen implies
  labeled blood speci- Further identification of the specificity                                            that a recipient can receive type-
  mens are critical.    of any antibody detected (using pan-                                              specific (ABO-Rh identical) blood
                        els of red cells of known antigenicity)                                           with minimal risk.




                                                                                                                                                                          Common Laboratory Tests: Selection and Interpretation
                        makes it possible to test donor blood                                            Technical Manual of the American
                        for the absence of the corresponding                                              Association of Blood Banks, 11th ed.
                        antigen.                                                                          American Association of Blood
                                                                                                          Banks, 1993.
Antidiuretic hor-       Antidiuretic hormone (vasopressin) is Increased in: Nephrogenic diabetes         Test very rarely indicated. Measure-
 mone, plasma            a hormone secreted from the poste-      insipidus, syndrome of inappropriate     ment of serum and urine osmolality
(ADH)                    rior pituitary that acts on the distal  antidiuretic hormone (SIADH). Drugs:     usually suffices.
                         nephron to conserve water and regu- nicotine, morphine, chlorpropamide,         Test not indicated in diagnosis of
If serum osmolality      late the tonicity of body fluids.        clofibrate, cyclophosphamide.             SIADH.
  >290 mosm/kg H2O:     Water deprivation provides both an      Normal relative to plasma osmolality     Patients with SIADH show decreased




                                                                                                                                                   Antidiuretic hormone
  2–12 pg/mL             osmotic and a volume stimulus for       in: Primary polydipsia.                  plasma sodium and decreased plasma
If serum osmolality      ADH release by increasing plasma       Decreased in: Central (neurogenic)        osmolality, usually with high urine
  <290 mosm/kg H2O:      osmolality and decreasing plasma        diabetes insipidus. Drugs: ethanol,      osmolality relative to plasma. These
  <2 pg/mL               volume.                                 phenytoin.                               findings in a normovolemic patient
                        Water administration lowers plasma                                                with normal thyroid and adrenal func-
Lavender                 osmolality and expands blood vol-                                                tion are sufficient to make the diagno-
$$$$                     ume, inhibiting the release of ADH                                               sis of SIADH without measuring
Draw in two chilled      by the osmoreceptor and the atrial                                               ADH itself.
 tubes and deliver to    volume receptor mechanisms.                                                     Semin Nephrol 1994;14:368.
 lab on ice. Specimen
 for serum osmolality
 must be drawn at




                                                                                                                                                                          53
 same time.
                                                                                                                                                                                     54
Test /Range/Collection             Physiologic Basis                          Interpretation                              Comments
Antiglobulin test,      Direct antiglobulin test demonstrates    Positive in: Autoimmune hemolytic          A positive DAT implies in vivo red




                                                                                                                                                                                     Pocket Guide to Diagnostic Tests
  direct, red cells      in vivo coating of washed red cells      anemia, hemolytic disease of the new-      cell coating by immunoglobulins or
(Direct Coombs, DAT) with globulins, in particular IgG            born, alloimmune reactions to recently     complement. Such red cell coating
                         and C3d.                                 transfused cells, and drug-induced         may or may not be associated with
Negative                Washed red cells are tested directly      hemolysis. Drugs: cephalosporins,          immune hemolytic anemia. Poly-
                         with antihuman globulin reagent.         levodopa, methadone, methyldopa,           specific and anti-IgG reagents detect




                                                                                                                                                       Antiglobulin test, direct
Lavender or red          DAT is positive (shows agglutina-        penicillin, phenacetin, quinidine.         approximately 500 molecules of IgG
                         tion) immediately when IgG coats                                                    per red cell, but autoimmune hemo-
$                        red cells. Complement or IgA coat-                                                  lytic anemia has been reported with
Blood anticoagulated     ing may only be demonstrated after                                                  IgG coating below this level.
  with EDTA is used to incubation at room temperature.                                                      10% of hospital patients have a posi-
  prevent in vitro                                                                                           tive DAT without clinical manifesta-
  uptake of complement                                                                                       tions of immune-mediated hemolysis.
  components. A red                                                                                         A false-positive DAT is often seen in
  top tube may be used,                                                                                      patients with hypergammaglobuline-
  if necessary.                                                                                              mia, eg, in some HIV-positive patients.
                                                                                                            Technical Manual of the American Asso-
                                                                                                             ciation of Blood Banks, 11th ed. Amer-
                                                                                                             ican Association of Blood Banks, 1993.
Antiglobulin test,       Demonstrates presence in patient’s      Positive in: Presence of alloantibody or   The technique is used in antibody




                                                                                                                                                       Antiglobulin test, indirect
  indirect, serum         serum of unexpected antibody to ABO autoantibody. Drugs: methyldopa.               detection and identification and in
(Indirect Coombs)         and Rh-compatible red blood cells.                                                 the major cross-match prior to trans-
                         First, the patient’s serum is incubated                                             fusion (see Type and Cross-Match,
Negative                  in vitro with reagent red cells and                                                p 175).
                          washed to remove unbound globu-                                                   Technical Manual of the American
Red                       lins. Then antihuman globulin (AHG,                                                Association of Blood Banks, 11th ed.
$                         Coombs) reagent is added. Aggluti-                                                 American Association of Blood
                          nation of red cells indicates that                                                 Banks, 1993.
                          serum contains antibodies to antigens
                          present on the reagent red cells.
  1-Antiprotease        α1-Antiprotease is an α1 globulin        Increased in: Inflammation, infection,      Smoking is a much more common
 ( 1-antitrypsin),       glycoprotein serine protease inhibitor rheumatic disease, malignancy, and           cause of chronic obstructive pulmo-




                                                                                                                                                     α1-Antiprotease
 serum                   (Pi) whose deficiency leads to exces- pregnancy because it is an acute phase         nary disease in adults than is
                         sive protease activity and panacinar     reactant.                                  α1-antiprotease deficiency.
110–270 mg/dL            emphysema in adults or liver disease Decreased in: Congenital l-antiprotease       N Engl J Med 1978;299:1045.
[1.1–2.7 g/L]            in children (seen as ZZ and SZ phe-      deficiency, nephrotic syndrome.            N Engl J Med 1978;299:1099.
                         notypes). Cirrhosis of the liver and                                               Curr Opin Pulm Med 1996;2:155.
Marbled                  liver cancer in adults are also associ-
$$                       ated with the Pi Z phenotype.




                                                                                                                                                                                 Common Laboratory Tests: Selection and Interpretation
Antistreptolysin O      Detects the presence of antibody to     Increased in: Recent infection with         Standardization of (Todd) units may
 titer, serum            the antigen streptolysin O produced     group A beta-hemolytic streptococci:        vary significantly from laboratory to
(ASO)                    by group A streptococci.                scarlet fever, erysipelas, streptococcal    laboratory.
                        Streptococcal antibodies appear about pharyngitis/tonsillitis (40–50%),             ASO titers are not useful in manage-
Children <5 years: <85; 2 weeks after infection. Titer rises to rheumatic fever (80–85%), poststrepto-       ment of acute streptococcal




                                                                                                                                                      Antistreptolysin O titer
5–19 years: <170         a peak at 4–6 weeks and may remain coccal glomerulonephritis. Some                  pharyngitis.
Adults: <85 Todd units elevated for 6 months to 1 year.          collagen-vascular diseases.                In patients with rheumatic fever, test
 (laboratory-specific) Test is based on the neutralization of Certain serum lipoproteins, bacterial           may be a more reliable indicator of
                         hemolytic activity of streptolysin O    growth products, or oxidized strepto-       recent streptococcal infection than
Marbled                  toxin by antistreptolysin O anti-       lysin O may result in inhibition of         throat culture.
$$                       bodies in serum.                        hemolysis and thus cause false-            An increasing titer is more suggestive
                                                                 positive results.                           of acute streptococcal infection than
                                                                                                             a single elevated level. Even with
                                                                                                             severe infection, ASO titers will
                                                                                                             rise in only 70–80% of patients.
                                                                                                            N Engl J Med 1970;282:23,78.
                                                                                                            J Clin Epidemiol 1993;46:1181.




                                                                                                                                                                                 55
                                                                                                                                                                                  56
Test /Range/Collection             Physiologic Basis                           Interpretation                              Comments
Antithrombin III (AT Antithrombin III is a serine protease        Increased by: Oral anticoagulants.           Congenital and acquired AT III




                                                                                                                                                                                  Pocket Guide to Diagnostic Tests
 III), plasma             inhibitor that protects against throm- Decreased in: Congenital and acquired          deficiency results in a hypercoagu-
84–123% (qualitative)     bus formation by inhibiting thrombin AT III deficiency (renal disease, chro-           lable state, venous thrombo-
22–39 mg/dL               and factors IXa, Xa, XIa, XIIa, plas- nic liver disease), oral contraceptive          embolism, and heparin resistance.
 (quantitative)           min, and kallikrein. It accounts for     use, chronic disseminated intravascular     Congenital AT III deficiency is pre-
                          70–90% of the anticoagulant activity coagulation, acute venous thrombosis             sent in 1 2000–1 5000 people and
Blue                      of human plasma. Its activity is         (consumption), and heparin therapy.          is autosomal codominant. Het-
$$                        enhanced 100-fold by heparin.                                                         erozygotes have AT III levels




                                                                                                                                                     Antithrombin III
Transport to lab on ice. There are two types of assay: func-                                                    20–60% of normal.
 Plasma must be sepa- tional (qualitative) and immunologic                                                     Semin Thromb Hemost 1982;8:276.
 rated and frozen in a    (quantitative). Since the immuno-                                                    Thromb Haemost 1993;69:231.
 polypropylene tube       logic assay cannot rule out functional
 within 2 hours.          AT III deficiency, a functional assay
                          should be ordered first. Functional
                          assays test AT III activity in inhibit-
                          ing thrombin or factor Xa. Given an
                          abnormal functional assay, the quan-
                          titative immunologic test indicates
                          whether there is decreased synthesis
                          of AT III or intact synthesis of a dys-
                          functional protein.
Aspartate amino-         Intracellular enzyme involved in amino Increased in: Acute viral hepatitis            Test is not indicated for diagnosis




                                                                                                                                                     Aspartate aminotransferase
 transferase, serum       acid metabolism. Present in large con- (ALT > AST), biliary tract obstruction         of myocardial infarction.
(AST, SGOT, GOT)          centrations in liver, skeletal muscle,  (cholangitis, choledocholithiasis),          AST/ALT ratio > 1 suggests cirrho-
                          brain, red cells, and heart. Released   alcoholic hepatitis and cirrhosis             sis in patients with hepatitis C.
0–35 IU/L                 into the bloodstream when tissue is     (AST > ALT), liver abscess, metastatic       Compr Ther 1994;20:50.
[0–0.58 µkat/L]           damaged, especially in liver injury.    or primary liver cancer; right heart fail-   Hosp Pract (Off Ed) Nov
(laboratory-specific)                                              ure, ischemia or hypoxia, injury to liver     1994;29:32.
                                                                  (“shock liver”), extensive trauma. Drugs     Am J Gastroenterol 1998;93:44.
Marbled                                                           that cause cholestasis or hepatotoxicity.
$                                                                Decreased in: Pyridoxine (vitamin B6)
                                                                  deficiency.
B cell immunoglobu- In general, the percentage of B lympho- Positive in: B cell neoplasms such as      Samples with > 10% of cells show-




                                                                                                                                                 B cell immunoglobulin heavy
                                                                                                                                                  chain gene rearrangement
 lin heavy chain gene cytes with identical immunoglobulin     lymphoma.                                 ing a given B cell rearrangement
 rearrangement          heavy chain gene rearrangements is                                              are considered positive. However,
Whole blood, bone       very low; in malignancies, however,                                             a large monoclonal population is
 marrow, or frozen tis- the clonal expansion of one popula-                                             consistent with—but not diagnos-
 sue                    tion leads to a large number of cells                                           tic of—malignancy.
                        with identical B cell immunoglobulin                                           Arch Path Lab Med 1988;112:117.
Lavender                heavy chain gene rearrangements.
$$$$                    Southern blot is used to identify a




                                                                                                                                                                               Common Laboratory Tests: Selection and Interpretation
                        monoclonal population.

bcr/abl translocation   Approximately 95% of chronic           Positive in: Chronic myelogenous        This assay will detect the 9;22




                                                                                                                                                 bcr/abl translocation
Blood                    myelogenous leukemia (CML) is          leukemia (sensitivity 95%) and acute    translocation if it has taken place in
                         associated with the “Philadelphia      lymphocytic leukemia (sensitivity       >10% of the cells. CML patients
Lavender                 chromosome,” a translocation that      10–15%).                                with bone marrow transplants can
$$$$                     moves the c-abl proto-oncogene                                                 be monitored for recurrence of dis-
                         from chromosome 9 to the break-                                                ease with this test.
                         point cluster (bcr) region of chromo-                                         N Engl J Med 1988;319:990.
                         some 22. Southern blot is used to
                         identify the translocation.




                                                                                                                                                                               57
                                                                                                                                                                  58
Test /Range/Collection             Physiologic Basis                          Interpretation                             Comments
Bilirubin, serum        Bilirubin, a product of hemoglobin    Increased in: Acute or chronic hepatitis, Assay of total bilirubin includes con-




                                                                                                                                                                  Pocket Guide to Diagnostic Tests
                         metabolism, is conjugated in the      cirrhosis, biliary tract obstruction, toxic jugated (direct) and unconjugated
0.1–1.2 mg/dL            liver to mono- and diglucuronides     hepatitis, neonatal jaundice, congenital (indirect) bilirubin plus delta bilirubin
[2–21 µmol/L]            and excreted in bile.                 liver enzyme abnormalities (Dubin-           (conjugated bilirubin bound to
                        Some conjugated bilirubin is bound to Johnson, Rotor’s, Gilbert’s, Crigler-         albumin).
Direct (conjugated to    serum albumin, so-called D (delta)    Najjar syndromes), fasting, hemolytic It is usually clinically unnecessary to
 glucuronide) biliru-    bilirubin.                            disorders. Hepatotoxic drugs.                fractionate total bilirubin. The frac-
 bin: 0.1–0.4 mg/dL     Elevated serum bilirubin occurs in                                                  tionation is unreliable by the diazo
 [<7 µmol/L];            liver disease, biliary obstruction,                                                reaction and may underestimate




                                                                                                                                                      Bilirubin
Indirect (unconjugated) or hemolysis.                                                                       unconjugated bilirubin. Only conju-
 bilirubin:                                                                                                 gated bilirubin appears in the urine,
 0.2–0.7 mg/dL                                                                                              and it is indicative of liver disease;
[<12 µmol/L]                                                                                                hemolysis is associated with
                                                                                                            increased unconjugated bilirubin.
Marbled                                                                                                    Persistence of delta bilirubin in serum
$$                                                                                                          in resolving liver disease means that
                                                                                                            total bilirubin does not effectively
                                                                                                            indicate the time course of resolution.
                                                                                                           Pediatrics 1992;89:80.
                                                                                                           Br J Hosp Med 1994;51:181.
                                                                                                           Pediatr Rev 1994;15:233.
Bleeding time           This is a test of platelet function, not a Increased in: Platelet disorders, throm- Test is useful as a screening test (with
                         test of coagulation factors.               bocytopenia, Bernard-Soulier syn-         aspirin challenge) for diagnosis of
2–10 minutes                                                        drome, thrombasthenia. Also elevated      von Willebrand’s disease and platelet
                                                                    in some forms of von Willebrand’s dis- disorders.
$$                                                                  ease, which is a disorder of factor VIII Test adds no clinically useful informa-
Test done by laboratory                                             coagulant activity and not primarily a    tion to the prediction of clinically sig-
 personnel. Simplate                                                platelet disorder. Drugs: aspirin and     nificant bleeding beyond that
 (presterilized device                                              other preparations containing aspirin.    obtained from the history, physical
 with spring-loaded                                                                                           examination, and other laboratory




                                                                                                                                                                          Common Laboratory Tests: Selection and Interpretation
                                                                                                                                                          Bleeding time
 blade) is used to make                                                                                       tests—platelet count, blood urea
 single cut 1 mm deep                                                                                         nitrogen (BUN), prothrombin time
 and 6 mm long on                                                                                             (PT), and partial thromboplastin time
 dorsal aspect of fore-                                                                                       (PTT).
 arm after inflation of                                                                                       In patients with no history of bleeding
 sphygmomanometer                                                                                             and no intake of nonsteroidal anti-
 to 40 mm Hg. Filter                                                                                          inflammatory drugs, an increased
 paper is used to                                                                                             bleeding time does not correlate with
 absorb blood from                                                                                            actual surgical bleeding.
 wound margins every                                                                                         Semin Thromb Hemost 1990;16:1.
 30 seconds, and time                                                                                        Blood 1994;84:3363.
 to cessation of bleed-                                                                                      Med Clin North Am 1994;78:577.
 ing is noted.




                                                                                                                                                                          59
                                                                                                                                                                               60
Test /Range/Collection             Physiologic Basis                          Interpretation                                Comments
Blood urea nitrogen,     Urea, an end product of protein me-      Increased in: Renal failure (acute or       Urease assay method commonly used.




                                                                                                                                                                               Pocket Guide to Diagnostic Tests
 serum                    tabolism, is excreted by the kidney.     chronic), urinary tract obstruction, de-   BUN/Cr ratio (normally 12 1–20 1) is
(BUN)                    BUN is directly related to protein        hydration, shock, burns, CHF, GI            decreased in acute tubular necrosis,




                                                                                                                                                         Blood urea nitrogen
                          intake and nitrogen metabolism and       bleeding. Nephrotoxic drugs                 advanced liver disease, low protein
8–20 mg/dL                inversely related to the rate of         (eg, gentamicin).                           intake, and following hemodialysis.
[2.9–7.1 mmol/L]          excretion of urea.                      Decreased in: Hepatic failure, nephrotic    BUN/Cr ratio is increased in dehydra-
                         Urea concentration in glomerular fil-      syndrome, cachexia (low-protein and         tion, GI bleeding, and increased
Marbled                   trate is the same as in plasma, but its high-carbohydrate diets).                    catabolism.
$                         tubular reabsorption is inversely                                                   Nursing 1994;24:88.
                          related to the rate of urine formation.                                             Ann Emerg Med 1992;21:713.
                          Thus, the BUN is a less useful mea-
                          sure of glomerular filtration rate than
                          the serum creatinine (Cr).
Brucella antibody,       Patients with acute brucellosis gener- Increased in: Brucella infection (except      This test will detect antibodies against
 serum                    ally develop an agglutinating anti-     B canis) (97% within 3 weeks of ill-         all of the Brucella species except
                          body titer of ≥ 1 160 within 3 weeks. ness); recent brucellergin skin test;          B canis.




                                                                                                                                                         Brucella antibody
<1 80 titer              The titer may rise during the acute      infections with Francisella tularensis,     A fourfold or greater rise in titer in
                          infection, with relapses, brucellergin Yersinia enterocolitica, salmonella,          separate specimens drawn 1–4 weeks
Marbled                   skin testing, or use of certain         Rocky mountain spotted fever; vacci-         apart is indicative of recent exposure.
$                         vaccines (see Interpretation).          nations for cholera and tularemia.          Final diagnosis depends on isolation of
                         The agglutinin titer usually declines   Normal in: B canis infection.                 organism by culture.
                          after 3 months or after successful                                                  J Clin Microbiol 1980;11:691.
                          therapy. Low titers may persist                                                     J Infect Dis 1989;159:219.
                          for years.                                                                          Rev Infect Dis 1991;13:359.




                                                                                                                                                         C-reactive protein
C-reactive protein,      Marker of inflammation.                  Increased in: Inflammatory states.            Elevated C-reactive protein level ap-
 serum                                                                                                         pears to be an independent risk factor
                                                                                                               for coronary heart disease events.
0–2 mg/dL                                                                                                     Ann Intern Med 1999;130:933.

Marbled
$
C1 esterase inhibitor   C1 esterase inhibitor (C1 INH) is an     Decreased in: Hereditary angioedema    C1 esterase inhibitor deficiency is an
 (C1 INH), serum         alpha-globulin, which controls the       (HAE) (85%) (15% of patients with      uncommon cause of angioedema.
                         first stage of the classic complement     HAE will have normal levels by         There are two subtypes of hereditary
Method-dependent         pathway and inhibits thrombin, plas- immunoassay, but the protein is non-       angioedema. In one, the protein is
                         min, and kallikrein. Deficiency re-       functional and levels determined by    absent; in the other, it is nonfunc-
Marbled                  sults in spontaneous activation of       the functional assay will be low).     tional. Acquired angioedema has
$$                       C1, leading to consumption of C2                                                been attributed to massive con-
                         and C4. The functional assay in-                                                sumption of C1 INH (presumably by
                         volves the measurement of C1 INH                                                tumor or lymphoma-related immune




                                                                                                                                                                            Common Laboratory Tests: Selection and Interpretation
                         as it inhibits the hydrolysis of a sub-                                         complexes) or to anti-C1 INH auto-
                         strate ester by C1 esterase. Immuno-                                            antibody.




                                                                                                                                                    C1 esterase inhibitor
                         assay of C1 INH is also available.                                             When clinical suspicion exists, a serum
                                                                                                         C4 level screens for HAE. Low levels
                                                                                                         of C4 are present in all cases during an
                                                                                                         attack. C1 esterase inhibitor levels are
                                                                                                         not indicated unless either the C4 level
                                                                                                         is low or there is a very high clinical
                                                                                                         suspicion of HAE in a patient with
                                                                                                         normal C4 during an asymptomatic
                                                                                                         phase between attacks. In acquired C1
                                                                                                         INH deficiency, the C1 level is also
                                                                                                         significantly decreased (often 10% of
                                                                                                         normal), whereas in HAE the C1 level
                                                                                                         is normal or only slightly decreased.
                                                                                                        Am J Med 1990;88:656.
                                                                                                        Ann Allergy 1991;67(2 Part 1):107.
                                                                                                        Med Clin North Am 1992;76:805.
                                                                                                        South Med J 1992;85:1084.




                                                                                                                                                                            61
                                                                                                                                                                      62
Test /Range/Collection               Physiologic Basis                            Interpretation                             Comments
C-peptide, serum           C-peptide is an inactive by-product of Increased in: Renal failure, ingestion of Test is most useful to detect factitious




                                                                                                                                                                      Pocket Guide to Diagnostic Tests
                            the cleavage of proinsulin to active   oral hypoglycemic drugs, insulinomas,     insulin injection (increased insulin,
0.8–4.0 ng/mL [µg/L]        insulin. Its presence indicates        B cell transplants.                       decreased C-peptide) or to detect
                            endogenous release of insulin.        Decreased in: Factitious hypoglycemia      endogenous insulin production in
Marbled                    C-peptide is largely excreted by the    due to insulin administration, pancre-    diabetic patients receiving insulin
$$$                         kidney.                                atectomy, type I diabetes mellitus        (C-peptide present).




                                                                                                                                                         C-peptide
Fasting sample                                                     (decreased or undetectable).             A molar ratio of insulin to C-peptide in
 preferred.                                                                                                  peripheral venous blood >1.0 in a
                                                                                                             hypoglycemic patient is consistent
                                                                                                             with surreptitious or inadvertent
                                                                                                             insulin administration but not
                                                                                                             insulinoma.
                                                                                                            Arch Intern Med 1977;137:625.
                                                                                                            Am J Med 1989;86:335.
                                                                                                            Arch Intern Med 1993;153:650.
Calcitonin, plasma         Calcitonin is a 32-amino-acid poly-        Increased in: Medullary thyroid carci- Test is useful to diagnose and monitor
                             peptide hormone secreted by the           noma (>500 pg/mL on two occasions),     medullary thyroid carcinoma, although
Male:                        parafollicular C cells of the thyroid.    Zollinger-Ellison syndrome, pernicious stimulation tests may be necessary
 <90 pg/mL [ng/L]          It decreases osteoclastic bone resorp-      anemia, pregnancy (at term), newborns, (eg, pentagastrin test).




                                                                                                                                                         Calcitonin
Female:                      tion and lowers serum calcium             carcinoma (breast, lung, pancreas),    Genetic testing is now available for the
 <70 pg/mL [ng/L]            levels.                                   chronic renal failure.                  diagnosis of multiple endocrine neo-
                                                                                                               plasia type II. (MEN II is the most
Green                                                                                                          common familial form of medullary
$$$                                                                                                            thyroid carcinoma.)
Fasting sample                                                                                                Mayo Clin Proc 1975;50:53.
 required. Place on ice.                                                                                      Ann Intern Med 1995;122:118.
Calcium, serum (Ca2+) Serum calcium is the sum of ionized Increased in: Hyperparathyroidism,             Need to know serum albumin to inter-
                         calcium plus complexed calcium and malignancies secreting parathyroid            pret calcium level. For every decrease
8.5–10.5 mg/dL           calcium bound to proteins (mostly     hormone–related protein (PTHrP)            in albumin by 1 mg/dL, calcium
[2.1–2.6 mmol/L]         albumin).                             (especially squamous cell carcinoma of     should be corrected upward by
Panic: <6.5 or          Level of ionized calcium is regulated  lung and renal cell carcinoma), vitamin    0.8 mg/dL. In 10% of patients with
  >13.5 mg/dL            by parathyroid hormone and            D excess, milk-alkali syndrome, multi-     malignancies, hypercalcemia is attrib-
                         vitamin D.                            ple myeloma, Paget’s disease of bone       utable to coexistent hyperparathy-




                                                                                                                                                   Calcium, serum
Marbled                                                        with immobilization, sarcoidosis, other    roidism, suggesting that serum PTH
$                                                              granulomatous disorders, familial          levels should be measured at initial




                                                                                                                                                                    Common Laboratory Tests: Selection and Interpretation
Prolonged venous sta-                                          hypocalciuria, vitamin A intoxication,     presentation of all hypercalcemic
  sis during collection                                        thyrotoxicosis, Addison’s disease.         patients (see pp 134 and 354).
  causes false increase                                        Drugs: antacids (some), calcium salts,    Ann Intern Med 1990;112:499.
  in serum calcium.                                            chronic diuretic use (eg, thiazides),     Nursing 1993;23:69.
                                                               lithium, others.                          Clin Endocrinol 1994;41:407.
                                                              Decreased in: Hypoparathyroidism, vit-
                                                               amin D deficiency, renal insufficiency,
                                                               pseudohypoparathyroidism, magne-
                                                               sium deficiency, hyperphosphatemia,
                                                               massive transfusion, hypoalbuminemia.




                                                                                                                                                                    63
                                                                                                                                                                64
Test /Range/Collection            Physiologic Basis                        Interpretation                        Comments
Calcium, ionized,      Calcium circulates in three forms: as Increased in: ↓ blood pH.              Ionized calcium measurements are not




                                                                                                                                                                Pocket Guide to Diagnostic Tests
 serum                  free Ca2+ (47%), protein-bound to      Decreased in: ↑ blood pH, citrate,    needed except in special circum-
                        albumin and globulins (43%), and as heparin, EDTA.                           stances, eg, massive blood transfu-
4.4–5.4 mg/dL           calcium-ligand complexes (10%)                                               sion, liver transplantation, neonatal
 (at pH 7.4)            (with citrate, bicarbonate, lactate,                                         hypocalcemia, and cardiac surgery.
[1.1–1.3 mmol/L]        phosphate, and sulfate). Protein                                             Validity of test depends on sample
                        binding is highly pH-dependent, and                                          integrity.




                                                                                                                                             Calcium, ionized
Whole blood specimen acidosis results in an increased free                                          Ann Clin Lab Sci 1991;21:297.
 must be collected      calcium fraction. Ionized Ca2+ is the
 anaerobically and      form that is physiologically active.
 anticoagulated with    Ionized calcium is a more accurate
 standardized amounts reflection of physiologic status than
 of heparin. Tourni-    total calcium in patients with altered
 quet application must serum proteins (renal failure, nephro-
 be brief. Specimen     tic syndrome, multiple myeloma,
 should be analyzed     etc), altered concentrations of
 promptly.              calcium-binding ligands, and acid-
                        base disturbances. Measurement of
Marbled                 ionized calcium is by ion-selective
$$                      electrodes.
Calcium, urine (UCa)    Ordinarily there is moderate urinary Increased in: Hyperparathyroidism,          Approximately one-third of patients
                         calcium excretion, the amount        osteolytic bone metastases, myeloma,        with hyperparathyroidism have nor-
100–300 mg/24 h          depending on dietary calcium,        osteoporosis, vitamin D intoxication,       mal urine calcium excretion.
[2.5–7.5 mmol/24 h or parathyroid hormone (PTH) level,        distal RTA, idiopathic hypercalciuria,     The extent of calcium excretion can be
 2.3–3.3 mmol/12 h]      and protein intake.                  thyrotoxicosis, Paget’s disease, Fan-       expressed as a urine calcium (UCa)/
                        Renal calculi occur much more often   coni’s syndrome, hepatolenticular           urine creatinine (UCr) ratio.
Urine bottle containing in hyperparathyroidism than in other degeneration, schistosomiasis, sar-         Normally,
 hydrochloric acid       hypercalcemic states.                coidosis, malignancy (breast, bladder),
$$$                                                           osteitis deformans, immobilization.                 U Ca ( mg dL )
                                                                                                                                    < 0.14




                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
Collect 24-hour urine                                         Drugs: acetazolamide, calcium salts,                 U Cr ( mg dL )
 or 12-hour overnight                                         cholestyramine, corticosteroids,
 urine.                                                       dihydrotachysterol, initial diuretic use   and
                                                              (eg, furosemide), others.
                                                             Decreased in: Hypoparathyroidism,                    U Ca ( mmol L )
                                                                                                                                    < 0.40




                                                                                                                                                     Calcium, urine
                                                              pseudohypoparathyroidism, rickets,                  U Cr ( mmol L )
                                                              osteomalacia, nephrotic syndrome,
                                                              acute glomerulonephritis, osteoblastic     Hypercalciuria is defined as a ratio
                                                              bone metastases, hypothyroidism,            >0.20 or >0.57, respectively.
                                                              celiac disease, steatorrhea, hypo-         Test is useful in the evaluation of renal
                                                              calciuric hypercalcemia, other causes       stones but is not usually needed for the
                                                              of hypocalcemia. Drugs: aspirin,            diagnosis of hyperparathyroidism,
                                                              bicarbonate, chronic diuretic use           which can be made using serum cal-
                                                              (eg, thiazides, chlorthalidone),            cium (see above) and PTH measure-
                                                              estrogens, indomethacin, lithium,           ments (see pp 134 and 354). It may be
                                                              neomycin, oral contraceptives.              useful in hypercalcemic patients to
                                                                                                          rule out familial hypocalciuric hyper-
                                                                                                          calcemia.
                                                                                                         In the diagnosis of hypercalciuria, UCa /
                                                                                                          UCr ratios in random single-voided
                                                                                                          urine specimens correlate well with
                                                                                                          24-hour calcium excretions.
                                                                                                         Arch Intern Med 1991;151:1587.




                                                                                                                                                                      65
                                                                                                         Miner Electrolyte Metab 1993;19:385.
                                                                                                                                                                           66
Test /Range/Collection             Physiologic Basis                           Interpretation                              Comments
Carbon dioxide           Bicarbonate-carbonic acid buffer is     Increased in: Primary metabolic alkalo- Total CO2 determination is indicated




                                                                                                                                                                           Pocket Guide to Diagnostic Tests
 (CO2), total, serum      one of the most important buffer        sis, compensated respiratory acidosis,      for all seriously ill patients on
(bicarbonate)             systems in maintaining normal           volume contraction, mineralocorticoid       admission.
                          body fluid pH.                           excess, congenital chloridorrhea.         If arterial blood gas studies are done,
22–28 meq/L [mmol/L] Total CO2 is measured as the sum of          Drugs: diuretics (eg, thiazide,             total CO2 test is redundant.




                                                                                                                                                       Carbon dioxide
Panic: <15 or             bicarbonate concentration plus          furosemide).                              Simultaneous measurement of pH and
  >40 meq/L [mmo/L]       carbonic acid concentration plus       Decreased in: Metabolic acidosis, com-       PCO2 is required to fully characterize
                          dissolved CO2.                          pensated respiratory alkalosis. Fanconi’s a patient’s acid-base status.
Marbled                  Since bicarbonate makes up 90–95%        syndrome, volume overload. Drugs:
$                         of the total CO2 content, total CO2 is acetazolamide, outdated tetracycline.
Do not leave exposed      a useful surrogate for bicarbonate
  to air since this will  concentration.
  cause falsely low
  CO2 levels.
Carboxyhemoglobin,       Carbon monoxide (CO) combines          Increased in: Carbon monoxide poison-        Test (if available within minutes,




                                                                                                                                                       Carboxyhemoglobin
 whole blood              irreversibly with hemoglobin at the    ing. Exposure to automobile exhaust or       together with O2 saturation by ox-
(HbCO)                    sites that normally bind oxygen. This smoke from fires. Cigarette smokers            imeter) is useful in evaluation of
                          produces a decrease in oxygen satu-    can have up to 9% carboxyhemoglobin,         CO poisoning.
< 9% [< 0.09]             ration and a shift in the oxyhemoglo- nonsmokers have <2%.                         PO2 is usually normal in CO poisoning.
                          bin dissociation curve, resulting in                                               Test measures carboxyhemoglobin
Lavender                  decreased release of oxygen to the                                                  spectrophotometrically.
$$                        tissues.                                                                           N Engl J Med 1989;321:1474.
Do not remove stopper.
Carcinoembryonic     CEA is an oncofetal antigen, a glyco-    Increased in: Colon cancer (72%), lung Screening: Test is not sensitive or spe-
 antigen, serum       protein associated with certain          cancer (76%), pancreatic cancer (91%), cific enough to be useful in cancer
(CEA)                 malignancies, particularly epithelial    stomach cancer (61%), cigarette smok- screening.
                      tumors.                                  ers, benign liver disease (acute 50%        Monitoring after surgery: Test is




                                                                                                                                                     Carcinoembryonic antigen
0–2.5 ng/mL [µg/L]                                             and chronic 90%), benign GI disease           used to follow progression of colon
                                                               (peptic ulcer, pancreatitis, colitis). Ele- cancer after surgery (elevated CEA
Marbled                                                        vations >20 ng/mL are generally asso-         levels suggest recurrence 3–6 months
$$                                                             ciated with malignancy. For breast            before other clinical indicators),
                                                               cancer recurrence (using 5 ng/mL              although such monitoring has not yet




                                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
                                                               cut-off), sensitivity = 44.4% and             been shown to improve survival rates.
                                                               specificity = 95.5%.                         If monitoring is done, the same assay
                                                                                                             method must be used consistently in
                                                                                                             order to eliminate any method-
                                                                                                             dependent variability.
                                                                                                           JAMA 1983;270:943.
                                                                                                           Ann Intern Med 1991;115:623.
                                                                                                           Br Cancer Treat 1995;37:209.




                                                                                                                                                                                67
                                                                                                                                                                      68
Test /Range/Collection             Physiologic Basis                          Interpretation                             Comments
CD4/CD8 ratio, whole Lymphocyte identification depends            Increased in: Rheumatoid arthritis, type Progressive decline in the number and




                                                                                                                                                                      Pocket Guide to Diagnostic Tests
  blood                    on specific cell surface antigens       I diabetes mellitus, SLE without renal     function of CD4 lymphocytes seems
                           (clusters of differentiation, CD),     disease, primary biliary cirrhosis,        to be the most characteristic immuno-
Ratio: 0.8–2.9             which can be detected with mono-       atopic dermatitis, Sézary syndrome,        logic defect in AIDS. Absolute CD4
CD4: 359–1725              clonal antibodies using flow            psoriasis, chronic autoimmune              measurement is particularly useful
  cells/µL (29–61%)        cytometry.                             hepatitis.                                 (more useful than the CD4/CD8 ratio)
CD8: 177–1106             CD4 cells are predominantly helper- Decreased in: AIDS/HIV infection, SLE in determining eligibility for therapy
  cells/µL (18–42%)        inducer cells of the immunologic       with renal disease, acute CMV infec-       (usually when CD4 < 500 cells/µL)
                           system. They react with peptide class tion, burns, graft-versus-host disease,     and in monitoring the progress of the




                                                                                                                                                      CD4/CD8 ratio
Lavender                   II major histocompatibility complex    sunburn, myelodysplasia syndromes,         disease.
$$$                        antigens and augment B cell re-        acute lymphocytic leukemia in re-         Most AIDS-defining infections occur
If an absolute CD4         sponses and T cell lymphokine          mission, recovery from bone marrow         when the CD4 count drops below 200
  count is required, also secretion. CD4 cells are the            transplantation, herpes infection, infec-  cells/µL.
  request a CBC and        major target of HIV-1.                 tious mononucleosis, measles, ataxia-     Absolute CD4 count depends, analyti-
  differential.           CD8 cells can be divided into suppres- telangiectasia, vigorous exercise.          cally, on the reliability of the white
                           sor cells, which decrease B cell                                                  blood cell differential count, as well
                           responses, and cytotoxic T cells.                                                 as on the percentage of CD4 cells
                                                                                                             identified using the appropriate
                                                                                                             monoclonal antibody.
                                                                                                            Hematol Oncol Clin North Am
                                                                                                             1991;5:215.
                                                                                                            Arch Intern Med 1994;154:1561.
Centromere antibody, Anticentromere antibodies are anti-   Positive in: CREST (70–90%), sclero-      In patients with connective tissue dis-
 serum                bodies to nuclear proteins of the     derma (10–15%), Raynaud’s disease         ease, the predictive value of a posi-
(ACA)                 kinetochore plate.                    (10–30%).                                 tive test is >95% for scleroderma or
                                                                                                      related disease (CREST, Raynaud’s




                                                                                                                                               Centromere antibody
Negative                                                                                              disease). Diagnosis of CREST is made
                                                                                                      clinically (calcinosis, Raynaud’s
Marbled                                                                                               disease, esophageal dysmotility,
$$                                                                                                    sclerodactyly, and telangiectasia).
                                                                                                     In the absence of clinical findings, the




                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
                                                                                                      test has low predictive value.
                                                                                                     (See also Autoantibodies table, p 367.)
                                                                                                     Rheum Dis Clin North Am
                                                                                                      1992;18:483.
                                                                                                     Ann Rheum Dis 1993;52:586.
                                                                                                     Clin Rheumatol 1994;13:427.
                                                                                                     Ann Rheum Dis 1995;54:148.
Ceruloplasmin, serum Ceruloplasmin, a 120,000–             Increased in: Acute and chronic inflam-    Slitlamp examination for Kayser-
                      160,000 MW α2-glycoprotein syn-       mation, pregnancy. Drugs: oral contra-    Fleischer rings and serum cerulo-




                                                                                                                                               Ceruloplasmin, serum
20–35 mg/dL           thesized by the liver, is the main    ceptives, phenytoin.                      plasmin level recommended for
[200–350 mg/L]        (95%) copper-carrying protein in     Decreased in: Wilson’s disease (hepato-    diagnosis of Wilson’s disease.
                      human serum.                          lenticular degeneration) (95%), CNS      Serum copper level is very rarely indi-
Marbled                                                     disease other than Wilson’s (15%),        cated. Screening all patients with
$$                                                          liver disease other than Wilson’s         liver disease is ineffective.
                                                            (23%), malabsorption, malnutrition,      5% of patients with Wilson’s disease
                                                            primary biliary cirrhosis, nephrotic      have low-normal levels of
                                                            syndrome, severe copper deficiency,        ceruloplasmin.
                                                            Menkes’ disease (X-linked inherited      Q J Med 1987;65:959.
                                                            copper deficiency).                       J Hepatol 1997;27:358.




                                                                                                                                                                      69
                                                                                                                                                                 70
Test /Range/Collection             Physiologic Basis                          Interpretation                             Comments
Chloride, serum (Cl−)    Chloride, the principal inorganic        Increased in: Renal failure, nephrotic    Test is helpful in assessing normal and




                                                                                                                                                                 Pocket Guide to Diagnostic Tests
                           anion of extracellular fluid, is impor- syndrome, renal tubular acidosis,          increased anion gap metabolic acido-
98–107 meq/L               tant in maintaining normal acid-base dehydration, overtreatment with saline, sis and in distinguishing hyper-
 [mmol/L]                  balance and normal osmolality.          hyperparathyroidism, diabetes insipi-     calcemia due to primary
                         If chloride is lost (as HCl or NH4Cl),    dus, metabolic acidosis from diarrhea     hyperparathyroidism (high serum
Marbled                    alkalosis ensues; if chloride is        (loss of HCO–), respiratory alkalosis,
                                                                                  3                          chloride) from that due to malignancy
$                          ingested or retained, acidosis          hyperadrenocorticism. Drugs: aceta-       (normal serum chloride).
                           ensues.                                 zolamide (hyperchloremic acidosis),      Exp Clin Endocrinol 1991;98:179.
                                                                   androgens, hydrochlorothiazide,          Crit Care Med 1992;20:227.
                                                                   salicylates (intoxication).




                                                                                                                                                      Chloride
                                                                  Decreased in: Vomiting, diarrhea,
                                                                   gastrointestinal suction, renal failure
                                                                   combined with salt deprivation, over-
                                                                   treatment with diuretics, chronic respi-
                                                                   ratory acidosis, diabetic ketoacidosis,
                                                                   excessive sweating, SIADH, salt-losing
                                                                   nephropathy, acute intermittent por-
                                                                   phyria, water intoxication, expansion
                                                                   of extracellular fluid volume, adrenal
                                                                   insufficiency, hyperaldosteronism,
                                                                   metabolic alkalosis. Drugs: chronic
                                                                   laxative or bicarbonate ingestion,
                                                                   corticosteroids, diuretics.
Cholesterol, serum      Cholesterol level is determined by       Increased in: Primary disorders: poly-       It is important to treat the cause of
                         lipid metabolism, which is in turn       genic hypercholesterolemia, familial          secondary hypercholesterolemia
Desirable <200           influenced by heredity, diet, and         hypercholesterolemia (deficiency of            (eg, hypothyroidism). Need to check
Borderline 200–239       liver, kidney, thyroid, and other        LDL receptors), familial combined             total cholesterol and HDL cholesterol
High risk >240 mg/dL     endocrine organ functions.               hyperlipidemia, familial dysbetalipo-         because cardiovascular risk may be
[Desirable <5.2         Total cholesterol (TC) = low density      proteinemia. Secondary disorders:             increased with relatively modest total
Borderline 5.2–6.1       lipoprotein (LDL) cholesterol + high hypothyroidism, uncontrolled diabetes             cholesterol elevation if HDL choles-
High risk                density lipoprotein (HDL) choles-        mellitus, nephrotic syndrome, biliary         terol is low.
  >6.2 mmol/L]           terol + (triglycerides [TG] / 5)         obstruction, anorexia nervosa, hepa-        National Cholesterol Education Program




                                                                                                                                                           Cholesterol

                                                                                                                                                                         Common Laboratory Tests: Selection and Interpretation
                         (valid only if TG < 400).                toma, Cushing’s syndrome, acute               Expert Panel has published clinical rec-
Marbled                 Since LDL cholesterol is the clinically intermittent porphyria. Drugs:                  ommendations for cholesterol manage-
$                        important entity, it is calculated as    corticosteroids.                              ment (see JAMA 1993 reference).
Fasting preferred for                                            Decreased in: Severe liver disease           Arch Intern Med 1988;148:36.
  LDL cholesterol.                                    TG          (acute hepatitis, cirrhosis, malignancy),   JAMA 1993;260:3015.
  HDL and total choles-        LDL = TC − HDL −                   hyperthyroidism, severe acute or chro-      Med Clin North Am 1994;78:117.
  terol can be measured                                5          nic illness, malnutrition, malabsorption    Circulation 1995;91:908.
  nonfasting.                                                     (eg, HIV), extensive burns, familial        JAMA 1998;279:1615.
                        This calculation is valid only if speci- (Gaucher’s disease, Tangier disease),
                         men is obtained fasting (in order to     abetalipoproteinemia, intestinal
                         obtain relevant triglyceride level).     lymphangiectasia.




                                                                                                                                                                         71
                                                                                                                                                                                                       72
Test /Range/Collection            Physiologic Basis                         Interpretation                               Comments
Chorionic              Human chorionic gonadotropin is a       Increased in: Pregnancy (including          Routine pregnancy testing is done by




                                                                                                                                                                                                       Pocket Guide to Diagnostic Tests
 gonadotropin,          glycoprotein made up of two sub-        ectopic pregnancy), hyperemesis gravi-      qualitative serum or urine hCG test.
   -subunit,            units (α and β). Human glycoproteins darum, trophoblastic tumors (hydatidi-         Test will be positive (>50 mIU/mL)




                                                                                                                                                      Chorionic gonadotropin, -subunit, quantitative
 quantitative, serum    such as LH, FSH, and TSH share the form mole, choriocarcinoma of uterus),           in most pregnant women at the time
(β-hCG)                 α subunit of hCG, but the β subunit     some germ cell tumors (teratomas of         of or shortly after the first missed
                        is specific for hCG. hCG is produced ovary or testicle, seminoma), ectopic           menstrual period.
Males and nonpregnant by trophoblastic tissue, and its detec- hCG production by other malignancies         Quantitative hCG testing is indicated
 females: undetectable tion in serum or urine is the basis for  (stomach, pancreas, lung, colon, liver).    for (1) the evaluation of suspected
 or <2 mIU/mL [IU/L] pregnancy testing. Serum hCG can           Failure of elevated serum levels to         ectopic pregnancy (where levels are
                        be detected as early as 24 hours after decrease after surgical resection of         lower than in normal pregnancy at the
Marbled                 implantation at a concentration of      trophoblastic tumor indicates metasta-      same gestational age) if the routine
$$                      5 mIU/mL.                               tic tumor; levels rising from normal        pregnancy test is negative; (2) the
                       During normal pregnancy, serum lev- indicate tumor recurrence.                       evaluation of threatened abortion. In
                        els double every 2–3 days and are      Decreasing over time: Threatened             both situations, hCG levels fail to
                        50–100 mIU/mL at the time of the        abortion.                                   demonstrate the normal early preg-
                        first missed menstrual period. Peak                                                  nancy increase.
                        levels are reached 60–80 days after                                                Test is also indicated for following the
                        the last menstrual period (LMP)                                                     course of trophoblastic and germ cell
                        (30,000–100,000 mIU/mL), and                                                        tumors.
                        levels then decrease to a plateau                                                  Hum Reprod 1992;7:701.
                        of 5,000–10,000 mIU/mL at about                                                    West J Med 1993;159:195.
                        120 days after LMP and persist                                                     Urology 1994;44:392.
                        until delivery.
Clostridium difficile     Clostridium difficile, a motile, gram- Positive in: Antibiotic-associated diar-      Definitive diagnosis of disease caused
 enterotoxin, stool       positive rod, is the major recognized   rhea (15–25%), antibiotic-associated        by C difficile toxin is by endoscopic
                          agent of antibiotic-associated diar-    colitis (50–75%), and pseudomembra-         detection of pseudomembranous




                                                                                                                                                       Clostridium difficile enterotoxin
Negative (≤1 10 titer)    rhea, which is toxigenic in origin (see nous colitis (90–100%). About 3% of         colitis.
                          Antibiotic-associated colitis, p 224).  healthy adults and 10–20% of hospital-     Direct examination of stool for leuko-
Urine or stool container There are two toxins (A and B) pro-      ized patients have C difficile in their      cytes, gram-positive rods, or blood is
$$$                       duced by C difficile. Cell culture is    colonic flora. There is also a high car-     not helpful.
Must be tested within     used to detect the cytopathic effect of rier rate of C difficile and its toxin in   Culture of C difficile is not routinely
 12 hours of collection the toxins, whose identity is con-        healthy neonates.                           performed, as it would isolate numer-




                                                                                                                                                                                          Common Laboratory Tests: Selection and Interpretation
 as toxin (B) is labile.  firmed by neutralization with                                                        ous nontoxigenic C difficile strains.
                          specific antitoxins.                                                                Rev Infect Dis 1990;12:S243.
                         Toxin A (more weakly cytopathic in                                                  Eur J Clin Microbiol 1996;15:561.
                          cell culture) is enterotoxic and pro-
                          duces enteric disease.
                         Toxin B (more easily detected in stan-
                          dard cell culture assays) fails to pro-
                          duce intestinal disease.
Clotting time, acti-    A bedside or operating room test that Prolonged in: Heparin therapy, severe Many consider this test unreliable. Re-
 vated, whole blood      assesses heparinization by measuring deficiency of clotting factors (except      producibility of prolonged ACTs is
(ACT)                    time taken for whole blood to clot.   factors VII and XIII), functional         poor.




                                                                                                                                                       Clotting time, activated
                                                               platelet disorders, afibrinogenemia, cir- Increasingly, the ACT has been used in
114–186 seconds                                                culating anticoagulants.                  the operating room, dialysis units,
                                                              Normal in: Thrombocytopenia, factor        critical care centers and during inter-
Special black tube                                             VII deficiency, von Willebrand’s           ventional cardiology/radiology proce-
$$                                                             disease.                                  dures to monitor anticoagulation and
Performed at patient                                                                                     titrate heparin dosages.
 bedside. Avoid trau-                                                                                   At centers without experience, should
 matic venipuncture,                                                                                     not be used to regulate therapeutic
 which may cause con-                                                                                    heparin dosage adjustments; use par-
 tamination with tissue                                                                                  tial thromboplastin time (PTT) instead.
 juices and decrease                                                                                    Am J Crit Care 1993;2(1):81.




                                                                                                                                                                                          73
 clotting time.                                                                                         Clin Cardiol 1994;17(7):357.
                                                                                                                                                                               74
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Coccidioides anti-    Screens for presence of antibodies to Positive in: Infection by coccidioides        Diagnosis is based upon culture and




                                                                                                                                                                               Pocket Guide to Diagnostic Tests
 bodies, serum or CSF Coccidioides immitis. Some centers      (90%).                                       serologic testing. Precipitin and CF
                       use the mycelial-phase antigen,       Negative in: Coccidioidin skin testing,       tests detect 90% of primary sympto-
Negative               coccidioidin, to detect antibody.      many patients with chronic cavitary          matic cases.
                      IgM antibodies appear early in disease coccidioides; 5% of meningeal coccid-        Precipitin test is most effective in




                                                                                                                                                     Coccidioides antibodies
Marbled                in 75% of patients, begin to decrease ioides is negative by CSF complement          detecting early primary infection or
$$                     after week 3, and are rarely seen      fixation (CF) test.                           an exacerbation of existing disease.
                       after 5 months. They may persist in                                                 Test is diagnostic but not prognostic.
                       disseminated cases, usually in the                                                 CF test becomes positive later than
                       immunocompromised.                                                                  precipitin test, and titers can be used
                      IgG antibodies appear later in the                                                   to assess severity of infection. Titers
                       course of the disease.                                                              rise as the disease progresses and
                      Meningeal disease may have negative                                                  decline as the patient improves.
                       serum IgG and require CSF IgG                                                      Enzyme immunoassay now available;
                       antibody titers.                                                                    data suggest good performance.
                                                                                                          N Engl J Med 1995;332:1077.
                                                                                                          Am J Clin Pathol 1997;107:148.
Cold agglutinins,        Detects antibodies that agglutinate red Increased in: Chronic cold agglutinin   In Mycoplasma pneumonia, titers rise
 plasma                   blood cells in the cold (strongly at    disease, lymphoproliferative disorders  early, are maximal at 3–4 weeks after
                          4°C, weakly at 24°C, and weakly or      (eg, Waldenström’s macroglobulin-       onset, and then disappear rapidly.




                                                                                                                                                     Cold agglutinins
< 1 20 titer              not at all at 37°C).                    emia), autoimmune hemolytic anemia, These antibodies are usually IgM anti-I
                         These antibodies are present in pri-     collagen-vascular diseases, M pneumo- antibodies distinct from antibodies to
Lavender or blue          mary atypical pneumonias due to         niae pneumonia, infectious mononucle- M pneumoniae.
$$                        Mycoplasma pneumoniae, in certain       osis, mumps orchitis, cytomegalovirus, A rise in cold agglutinin antibody titer
Specimen should be        autoimmune hemolytic anemias, and tropical diseases (eg, trypanosomiasis). is suggestive of recent mycoplasma
 kept at 37 °C.           in normal persons (not clinically                                               infection but is found in other dis-
                          significant).                                                                    eases.
                                                                                                         N Engl J Med 1977;297:583.
Complement C3,    The classic and alternative comple-    Increased in: Many inflammatory con- Complement C3 levels may be useful
 serum             ment pathways converge at the C3       ditions as an acute phase reactant,       in following the activity of immune
                   step in the complement cascade.        active phase of rheumatic diseases (eg,   complex diseases.
64–166 mg/dL       Low levels indicate activation by one rheumatoid arthritis, SLE), acute viral The best test to detect inherited defi-
[640–1660 mg/L]    or both pathways.                      hepatitis, myocardial infarction, cancer, ciencies is CH50.
                  Most diseases with immune complexes diabetes mellitus, pregnancy, sarcoido- N Engl J Med 1987;316:1525.
Marbled            will show decreased C3 levels.         sis, amyloidosis, thyroiditis.




                                                                                                                                               Complement C3
$$                Test is usually performed as an        Decreased by: Decreased synthesis (pro-
                   immunoassay (by radial immuno-         tein malnutrition, congenital deficiency,




                                                                                                                                                               Common Laboratory Tests: Selection and Interpretation
                   diffusion or nephelometry).            severe liver disease), increased catabo-
                                                          lism (immune complex disease, mem-
                                                          branoproliferative glomerulonephritis
                                                          [75%], SLE, Sjögren’s syndrome,
                                                          rheumatoid arthritis, disseminated
                                                          intravascular coagulation, paroxysmal
                                                          nocturnal hemoglobinuria, autoimmune
                                                          hemolytic anemia, gram-negative
                                                          bacteremia), increased loss (burns,
                                                          gastroenteropathies).
Complement C4,    C4 is a component of the classic com- Increased in: Various malignancies        Low C4 accompanies acute attacks of
 serum             plement pathway. Depressed levels     (not clinically useful).                  hereditary angioedema, and C4 is




                                                                                                                                               Complement C4
                   usually indicate classic pathway     Decreased by: Decreased synthesis          used as a first-line test for the disease.
15– 45 mg/dL       activation.                           (congenital deficiency), increased         C1 esterase inhibitor levels are not
[150–450 mg/L]    Test is usually performed as an        catabolism (SLE, rheumatoid arthritis,    indicated for the evaluation of heredi-
                   immunoassay and not a functional      proliferative glomerulonephritis, hered- tary angioedema unless C4 is low.
Marbled            assay.                                itary angioedema), and increased loss    Congenital C4 deficiency occurs with
$$                                                       (burns, protein-losing enteropathies).    an SLE-like syndrome.
                                                                                                  N Engl J Med 1987;316:1525.
                                                                                                  Am J Med 1990;88:656.




                                                                                                                                                               75
                                                                                                                                                                       76
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Complement CH50,         The quantitative assay of hemolytic     Decreased with: >50–80% deficiency of This is a functional assay of biologic




                                                                                                                                                                       Pocket Guide to Diagnostic Tests
 plasma or serum          complement activity depends on the      classic pathway complement compo-      activity. Sensitivity to decreased
(CH50)                    ability of the classic complement       nents (congenital or acquired          levels of complement components




                                                                                                                                                     Complement CH50
                          pathway to induce hemolysis of red      deficiencies).                          depends on exactly how the test is
22– 40 U/mL               cells sensitized with optimal          Normal in: Deficiencies of the alterna-  performed.
(laboratory-specific)      amounts of anti-red cell antibodies.    tive pathway complement components. It is used to detect congenital and
                         For precise titrations of hemolytic                                             acquired severe deficiency disorders
Marbled                   complement, the dilution of serum                                              of the classic complement pathway.
$$$                       that will lyse 50% of the indicator                                           N Engl J Med 1987;316:1525.
                          red cells is determined as the CH50.
                         This arbitrary unit depends on the
                          conditions of the assay and is
                          therefore laboratory-specific.
Cortisol, plasma         Release of corticotropin-releasing     Increased in: Cushing’s syndrome, acute   Cortisol levels are useful only in the
 or serum                 factor (CRF) from the hypothalamus illness, surgery, trauma, septic shock,       context of standardized suppression
                          stimulates release of ACTH from the depression, anxiety, alcoholism, starva-     or stimulation tests. (See Cosyntropin
8:00 AM: 5–20 µg/dL       pituitary, which in turn stimulates    tion, chronic renal failure, increased    stimulation test, p 77, and Dexa-
[140–550 nmol/L]          release of cortisol from the adrenal.  CBG (congenital, pregnancy,               methasone suppression tests, p 83).




                                                                                                                                                     Cortisol
                          Cortisol provides negative feedback    estrogen therapy).                       Circadian fluctuations in cortisol levels
Marbled, lavender,        to this system.                       Decreased in: Addison’s disease;           limit usefulness of single measure-
 or green                Test measures both free cortisol and    decreased CBG (congenital, liver          ments.
$$                        cortisol bound to cortisol-binding     disease, nephrotic syndrome).            Analysis of diurnal variation of corti-
                          globulin (CBG).                                                                  sol is not useful diagnostically.
                         Morning levels are higher than                                                   Crit Care Clin 1991;7:23.
                          evening levels.                                                                 Endocrinol Metab Clin North Am
                                                                                                           1994;23:511.
Cortisol (urinary         Urinary free cortisol measurement is Increased in: Cushing’s syndrome,      This test replaces both the assessment
 free), urine              useful in the initial evaluation of sus- acute illness, stress.             of 17-hydroxycorticosteroids and the
                           pected Cushing’s syndrome (see           Not Increased in: Obesity.         17-ketogenic steroids in the initial




                                                                                                                                                   Cortisol (urinary free)
10–110 µg/24 h             Cushing’s syndrome algorithm,                                               diagnosis of Cushing’s syndrome.
[30–300 nmol/d]            p 340).                                                                    Not useful for the diagnosis of adrenal
                                                                                                       insufficiency.
Urine bottle containing                                                                               A shorter (12-hour) overnight collection
 boric acid.                                                                                           and measurement of the ratio of urine
$$$                                                                                                    free cortisol to urine creatinine appears




                                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
Collect 24-hour urine.                                                                                 to perform nearly as well as a 24-hour
                                                                                                       collection for urine free cortisol.
                                                                                                      Ann Intern Med 1992;116:211.
                                                                                                      Clin Endocrinol 1998;48:503.
Cosyntropin stimula- Cosyntropin (synthetic ACTH pre-           Decreased in: Adrenal insufficiency,   Test does not distinguish primary from
 tion test, serum or     paration) stimulates the adrenal to     pituitary insufficiency, AIDS.         secondary (pituitary) adrenal insuffi-




                                                                                                                                                   Cosyntropin stimulation test
 plasma                  release cortisol.                                                             ciency, since in secondary adrenal
                        A normal response is a doubling of                                             insufficiency the atrophic adrenal
Marbled, green, or       basal levels or an increment of                                               may be unresponsive to cosyntropin.
 lavender                7 µg/dL (200 nmol/L) to a level                                               Test may not reliably detect pituitary
$$$                      above 18 µg/dL (>504 nmol/L).                                                 insufficiency.
First draw a cortisol   A poor cortisol response to cosyntro-                                         Metyrapone test (p 127) may be useful
 level. Then adminis-    pin indicates adrenal insufficiency                                            to assess the pituitary-adrenal axis.
 ter cosyntropin (1 µg   (see Adrenocortical insufficiency                                             Crit Care Clin 1991;7:23.
 or 0.25 mg IV). Draw algorithm, Fig. 8-3, p 338).                                                    Resp Med 1991;85:511.
 another cortisol level                                                                               J Clin Endocrinol Metab
 in 30 minutes.                                                                                        1998;83:2726.




                                                                                                                                                                                  77
                                                                                                                                                                      78
Test /Range/Collection            Physiologic Basis                        Interpretation                              Comments
Creatine kinase, serum Creatine kinase splits creatine phos-   Increased in: Myocardial infarction,     CK is as sensitive a test as aldolase for




                                                                                                                                                                      Pocket Guide to Diagnostic Tests
(CK)                    phate in the presence of ADP to         myocarditis, muscle trauma,              muscle damage, so aldolase is not
                        yield creatine and ATP.                 rhabdomyolysis, muscular dystrophy,      needed.
32–267 IU/L            Skeletal muscle, myocardium, and         polymyositis, severe muscular exertion, During a myocardial infarction (MI),
[0.53–4.45 µkat/L]      brain are rich in the enzyme.           malignant hyperthermia, hypothyroid-     serum CK level rises rapidly (within
 (method-dependent) CK is released by tissue damage.            ism, cerebral infarction, surgery,       3–5 hours); elevation persists for




                                                                                                                                                    Creatine kinase
                                                                Reye’s syndrome, tetanus, generalized    2–3 days post-myocardial infarction.
Marbled                                                         convulsions, alcoholism, IM injections, Total CK is not specific enough for use
$                                                               DC countershock. Drugs: clofibrate,       in diagnosis of MI, but a normal total
                                                                HMG-Co A reductase inhibitors.           CK has a high negative predictive
                                                                                                         value. A more specific test is needed
                                                                                                         for diagnosis of MI (eg, CK-MB or
                                                                                                         cardiac troponin I). Cardiac troponin I
                                                                                                         and CK-MB or CK-MB mass concen-
                                                                                                         tration are better markers for myocar-
                                                                                                         dial infarction.
                                                                                                        Br Heart J 1994;72:112.
Creatine kinase MB,   CK consists of 3 isoenzymes, made up Increased in: Myocardial infarction,       CKMB is a relatively specific test for
 serum (CKMB)          of 2 subunits, M and B. The fraction cardiac trauma, certain muscular dys-      MI. It appears in serum approxi-
 enzyme activity       with the greatest electrophoretic    trophies, and polymyositis. Slight per-    mately 4 hours after infarction, peaks
                       mobility is CK1 (BB); CK2 (MB) is    sistent elevation reported in a few        at 12–24 hours, and declines over
<16 IU/L               intermediate and CK3 (MM) moves      patients on hemodialysis.                  48–72 hours. CKMB mass concentra-
[<0.27 µkat/L] or <4% slowest towards the anode.                                                       tion is a more sensitive marker of MI
 of total CK or       Skeletal muscle is characterized by                                              than CKMB isoenzymes or total CK
 <7 µg/L mass units    isoenzyme MM and brain by                                                       within 4–12 hours after infarction.
 (laboratory-specific)  isoenzyme BB.                                                                   Cardiac troponin I levels are useful in




                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
                                                                                                                                                 Creatine kinase MB
                      Myocardium has approximately 40%                                                 the late (after 48 hours) diagnosis of
Marbled                MB isoenzyme.                                                                   MI since, unlike CKMB, levels
$$                    Assay techniques include isoenzyme                                               remain elevated for 5–7 days. Within
                       separation by electrophoresis (iso-                                             48 hours, sensitivity and specificity of
                       enzyme activity units) or immuno-                                               troponin I are similar to CKMB.
                       assay using antibody specific for                                                Specificity of troponin I is higher than
                       MB fraction (mass units).                                                       CKMB in patients with skeletal mus-
                                                                                                       cle injury or renal failure, or post-
                                                                                                       operatively. Cardiac troponin I is
                                                                                                       therefore the preferred test.
                                                                                                      Estimation of CKMM and CKBB is
                                                                                                       not clinically useful. Use total CK.
                                                                                                      Br Heart J 1994;72:112.
                                                                                                      Clin Chem 1994;40(7 Pt1):1291.
                                                                                                      N Eng1 J Med 1994;330:670.
                                                                                                      N Eng1 J Med 1994;331:561.




                                                                                                                                                                      79
                                                                                                                                                             80
Test /Range/Collection            Physiologic Basis                       Interpretation                           Comments
Creatinine, serum        Endogenous creatinine is excreted by Increased in: Acute or chronic renal   In alkaline picrate method, substances




                                                                                                                                                             Pocket Guide to Diagnostic Tests
(Cr)                      filtration through the glomerulus and failure, urinary tract obstruction,    other than Cr (eg, acetoacetate,
                          by tubular secretion. Creatinine      nephrotoxic drugs, hypothyroidism.    acetone, β-hydroxybutyrate,
0.6–1.2 mg/dL             clearance is an acceptable clinical  Decreased in: Reduced muscle mass.     α-ketoglutarate, pyruvate, glucose)
[50–100 µmol/L]           measure of glomerular filtration rate                                        may give falsely high results. There-




                                                                                                                                                Creatinine
                          (GFR), though it sometimes overesti-                                        fore, patients with diabetic ketoacido-
Marbled                   mates GFR (eg, in cirrhosis).                                               sis may have spuriously elevated Cr.
$                        For each 50% reduction in GFR, serum                                        Cephalosporins may spuriously
                          creatinine approximately doubles.                                           increase or decrease Cr measurement.
                                                                                                     Increased bilirubin may spuriously
                                                                                                      decrease Cr.
                                                                                                     Clin Chem 1990;36:1951.
                                                                                                     Ann Pharmacother 1993;27:622.
Creatinine clearance, Widely used test of glomerular filtra- Increased in: High cardiac output, exer- Serum Cr may, in practice, be a more
 (C1Cr)                  tion rate (GFR). Theoretically reli-  cise, acromegaly, diabetes mellitus    reliable indicator of renal function
                         able, but often compromised by        (early stage), infections, hypo-       than 24-hour C1Cr unless urine collec-
Adults: 90–130 mL/       incomplete urine collection.          thyroidism.                            tion is carefully monitored. An 8-hour
 min/1.73 m2 BSA        Creatinine clearance is calculated    Decreased in: Acute or chronic renal    collection provides results similar to
                         from measurement of urine creati-     failure, decreased renal blood flow     those obtained by a 24-hour collection.
$$                       nine (UCr [mg/dL]), plasma/serum      (shock, hemorrhage, dehydration,      C1Cr will overestimate GFR to the
Collect carefully timed creatinine (PCr [mg/dL]), and urine    CHF). Drugs: nephrotoxic drugs.        extent that Cr is secreted by the renal
 24-hour urine and       flow rate (V [mL/min]) according to                                           tubules (eg, in cirrhosis).




                                                                                                                                                                       Common Laboratory Tests: Selection and Interpretation
 simultaneous            the formula:                                                                C1Cr can be estimated from the serum




                                                                                                                                                Creatinine clearance
 serum/plasma creati-                                                                                 creatinine using the following formula:
 nine sample. Record                              U Cr × V
 patient’s weight and          Cl Cr ( mL min ) =                                                         Cl Cr       (140 − Age) × Wt( kg)
                                                     PCr
 height.                                                                                               (mL min) =            72 × PCr
                        where
                                                                                                     Crit Care Med 1993;21:1487.
                                            24-hour urine                                            Pharmacotherapy 1993;13:135.
                                            volume(mL)                                               Arch Intern Med 1994;154:201.
                            V( mL min ) =
                                                  1440

                        Creatinine clearance is often “cor-
                         rected” for body surface area (BSA
                         [m2]) according to the formula:

                            Cl Cr         Cl Cr      1.73
                                    =              ×
                         (corrected) ( uncorrected) BSA




                                                                                                                                                                       81
                                                                                                                                                                              82
Test /Range/Collection            Physiologic Basis                         Interpretation                               Comments
Cryoglobulins, serum     Cryoglobulins are immunoglobulins      Increased in: Immunoproliferative disor-   All types of cryoglobulins may cause




                                                                                                                                                                              Pocket Guide to Diagnostic Tests
                          (IgG, IgM, IgA, or light chains)       ders (multiple myeloma, Waldenström’s      cold-induced symptoms, including
<0.12 mg/mL               which precipitate on exposure to       macroglobulinemia, chronic lympho-         Raynaud’s phenomenon, vascular
                          the cold.                              cytic leukemia, lymphoma), collagen-       purpura, and urticaria.
Marbled                  Type I cryoglobulins (25%) are mono- vascular disease (SLE, polyarteritis         Patients with type II and III cryoglobu-
$                         clonal proteins, most commonly IgM, nodosa, rheumatoid arthritis), hemolytic      linemia often have immune complex




                                                                                                                                                       Cryoglobulins
Must be immediately       occasionally IgG, and rarely IgA or    anemia, essential mixed cryoglobuline-     disease, with vascular purpura, arthri-
  transported to lab      Bence Jones protein, seen in multiple mia, hepatitis B and C infection.           tis, and nephritis.
  at 37°C                 myeloma and Waldenström’s                                                        Typing of cryoglobulins by electro-
                          macroglobulinemia.                                                                phoresis is not necessary for diag-
                         Type II (25%) are mixed cryoglobu-                                                 nosis or clinical management.
                          lins with a monoclonal component                                                 About 50% of essential mixed cryo-
                          (usually IgM but occasionally IgG or                                              globulinemia patients have evidence
                          IgA) that complexes with autologous                                               of hepatitis C infection.
                          normal IgG in the cryoprecipitate.                                               Am J Med 1980;68:757.
                         Type III (50%) are mixed polyclonal                                               JAMA 1982;248:2670.
                          cryoglobulins (IgM and IgG).                                                     Am J Med 1994;96:124.
Cryptococcal antigen, The capsular polysaccharide of Cryp- Increased in: Cryptococcal infection.           False-positive and false-negative results
 serum or CSF          tococcus neoformans potentiates                                                      have been reported. False-positives
                       opportunistic infections by the yeast.                                               due to rheumatoid factor can be re-




                                                                                                                                                       Cryptococcal antigen
Negative               The cryptococcal antigen test used is                                                duced by pretreatment of serum using
                       often a latex agglutination test.                                                    pronase before testing. Sensitivity and
Marbled (serum) or                                                                                          specificity of serum cryptococcal anti-
 glass or plastic                                                                                           gen titer for cryptococcal meningitis
 tube (CSF)                                                                                                 are 91% and 83%, respectively.
$$                                                                                                         Ninety-six percent of cryptococcal
                                                                                                            infections occur in AIDS patients.
                                                                                                           Infect Immun 1994;62:1507.
                                                                                                           J Clin Microbiol 1994;32:2158.
                                                                                                           J Med Assoc Thai 1999;82:65.
Cytomegalovirus         Detects the presence of antibody to   Increased in: Previous or active CMV      Serial specimens exhibiting a greater
 antibody, serum         CMV, either IgG or IgM.               infection. False-positive CMV IgM         than fourfold titer rise suggest a recent
(CMV)                   CMV infection is usually acquired      tests occur when rheumatoid factor or     infection. Active CMV infection must




                                                                                                                                                     Cytomegalovirus antibody
                         during childhood or early adulthood. infectious mononucleosis is present.       be documented by viral isolation.
Negative                 By age 20–40 years, 40–90% of the                                              Useful for screening of potential organ
                         population has CMV antibodies.                                                  donors and recipients.
Marbled                                                                                                 Detection of CMV IgM antibody in the
$$$                                                                                                      serum of a newborn usually indicates
                                                                                                         congenital infection. Detection of




                                                                                                                                                                                                 Common Laboratory Tests: Selection and Interpretation
                                                                                                         CMV IgG antibody is not diagnostic,
                                                                                                         since maternal CMV IgG antibody
                                                                                                         passed via the placenta can persist in
                                                                                                         newborn’s serum for 6 months.
                                                                                                        Rev Infect Dis 1988;10:S468.
Dexamethasone sup- In normal patients, dexamethasone          Positive in: Cushing’s syndrome (98% Good screening test for Cushing’s syn-




                                                                                                                                                     Dexamethasone suppression test (low-dose)
 pression test (single  suppresses the 8:00 AM serum corti-    sensitivity, 98% specificity in lean out- drome. If this test is abnormal, use
 low-dose, overnight), sol level to below 5 µg/dL.             patients), obese patients (13%), hospi-     high-dose test (see below) to deter-
 serum                 Patients with Cushing’s syndrome        talized or chronically ill patients (23%). mine etiology. (See also Cushing’s
                        have 8:00 AM levels >10 µg/dL                                                      syndrome algorithm, p 340.)
8:00 AM serum cortisol (>276 nmol/L).                                                                     Patients taking phenytoin may fail to
 level: <5 µg/dL                                                                                           suppress because of enhanced
[<140 nmol/L]                                                                                              dexamethasone metabolism.
                                                                                                          Depressed patients may also fail to
$$                                                                                                         suppress morning cortisol level.
Give 1 mg dexametha-                                                                                      Ann Clin Biochem 1997;
 sone at 11:00 PM. At                                                                                      34(Part 3):222.
 8:00 AM, draw serum
 cortisol level.




                                                                                                                                                                                                 83
                                                                                                                                                                                              84
Test /Range/Collection            Physiologic Basis                       Interpretation                             Comments
Dexamethasone sup-     Suppression of plasma cortisol levels Positive in: Cushing’s disease (88–92% Test indicated only after a positive low-




                                                                                                                                                                                              Pocket Guide to Diagnostic Tests
 pression test (high-   to < 50% of baseline with dexam-      sensitivity; specificity 57–100%).      dose dexamethasone suppression test.




                                                                                                                                                 Dexamethasone suppression test (high-dose)
 dose, overnight),      ethasone indicates Cushing’s disease                                        Sensitivity and specificity depend on
 serum                  (pituitary-dependent ACTH hyper-                                             sampling time and diagnostic criteria.
                        secretion) and differentiates this                                          The ovine corticotropin-releasing hor-
8:00 AM serum cortisol from adrenal and ectopic Cushing’s                                            mone (CRH) stimulation test and bila-
 level:                 syndrome (see Cushing’s syndrome                                             teral sampling of the inferior petrosal
 <5 µg/dL               algorithm, p 340).                                                           sinuses combined with CRH adminis-
[<140 nmol/L]                                                                                        tration are being evaluated for the def-
                                                                                                     initive diagnosis of Cushing’s disease.
$$                                                                                                  Measurement of urinary 17-hydroxy-
Give 8 mg dexa-                                                                                      corticosteroids has been replaced in
 methasone dose at                                                                                   this test by measurement of serum
 11:00 PM. At                                                                                        cortisol.
 8:00 AM, draw                                                                                      Ann Intern Med 1986;104:180.
 cortisol level.                                                                                    Ann Intern Med 1990;112:434.
                                                                                                    J Clin Endocrinol Metab 1994;78:418.
                                                                                                    N Engl J Med 1994;331:629.
                                                                                                    Medicine 1995;74:74.
                                                                                                    Ann Intern Med 1994;121:318.
                         IgG or IgM antibodies directed                                                High titers are seen only in SLE.




                                                                                                                                                 Double-stranded DNA antibody
Double-stranded-                                              Increased in: Systemic lupus erythe-
 DNA antibody             against host double-stranded DNA.    matosus (60–70% sensitivity, 95%        Titers of ds-DNA antibody correlate
 (ds-DNA Ab), serum                                            specificity) based on >1 10 titer.        well with disease activity and with
                                                              Not increased in: Drug-induced lupus.     occurrence of glomerulonephritis.
<1 10 titer                                                                                            (See also Autoantibodies table, p 367.)
                                                                                                       West J Med 1987;147:210.
Marbled                                                                                                Clin Immunol Immunopathol
$$                                                                                                      1988;47:121.
Epstein-Barr virus   Antiviral capsid antibodies (anti-VCA) Increased in: EB virus infection, infec-       Most useful in diagnosing infectious
 antibodies, serum    (IgM) often reach their peak at         tious mononucleosis.                          mononucleosis in patients who have
(EBV Ab)              clinical presentation and last up to   Antibodies to the diffuse (D) form of          the clinical and hematologic criteria
                      3 months; anti-VCA IgG antibodies       antigen (detected in the cytoplasm and        for the disease but who fail to develop




                                                                                                                                                      Epstein-Barr virus antibodies
Negative              last for life.                          nucleus of infected cells) are greatly        the heterophile agglutinins (10%) (see
                     Early antigen antibodies (anti-EA) are elevated in nasopharyngeal carcinoma.           Heterophile agglutination, p 107).
Marbled               next to develop, are most often posi- Antibodies to the restricted (R) form of       EBV antibodies cannot be used to
$$                    tive at 1 month after presentation,     antigen (detected only in the cytoplasm       diagnose “chronic” mononucleosis.
                      typically last for 2–3 months, and      of infected cells) are greatly elevated in    Chronic fatigue syndrome is not




                                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
                      may last up to 6 months in low titers. Burkitt’s lymphoma.                            caused by EBV.
                      Anti-EA may also be found in some                                                    The best indicator of primary infection
                      patients with Hodgkin’s disease,                                                      is a positive anti-VCA IgM (check for
                      chronic lymphocytic leukemia, and                                                     false-positives caused by rheumatoid
                      some other malignancies.                                                              factor).
                     Anti-EB nuclear antigen (anti-EBNA)                                                   Rose NR et al (editors): Manual of
                      antibody begins to appear in a minor-                                                 Clinical Laboratory Immunology,
                      ity of patients in the third or fourth                                                4th ed. American Society for
                      week but is uniformly present by                                                      Microbiology, 1992.
                      6 months.                                                                            J Clin Microbiol 1996;34:3240.
Erythrocyte count,   Erythrocytes are counted by auto-        Increased in: Secondary polycythemia         Lab Med 1983;14:509.
 whole blood          mated instruments using electrical       (hemoconcentration), polycythemia




                                                                                                                                                      Erythrocyte count
(RBC count)           impedance or light scattering.           vera. Spurious increase with increased
                                                               white blood cells.
4.2–5.6 × 106/µL                                              Decreased in: Anemia. Spurious
[× 1012/L]                                                     decrease with autoagglutination.

Lavender
$




                                                                                                                                                                                      85
                                                                                                                                                                                          86
Test /Range/Collection             Physiologic Basis                          Interpretation                               Comments
Erythrocyte sedimen- In plasma, erythrocytes (red blood        Increased in: Infections (osteomyelitis,      There is a good correlation between




                                                                                                                                                                                          Pocket Guide to Diagnostic Tests
  tation rate, whole    cells [RBCs]) usually settle slowly.    pelvic inflammatory disease [75%]),            ESR and C-reactive protein, but ESR




                                                                                                                                                         Erythrocyte sedimentation rate
  blood                 However, if they aggregate for any      inflammatory disease (temporal arteri-         is less expensive.
(ESR)                   reason (usually because of plasma       tis, polymyalgia rheumatica, rheumatic       Test is useful and indicated only for
                        proteins called acute phase reactants, fever), malignant neoplasms, parapro-          diagnosis and monitoring of temporal
Male: <10               eg, fibrinogen) they settle rapidly.     teinemias, anemia, pregnancy, chronic         arteritis and polymyalgia rheumatica.
Female: <15 mm/h       Sedimentation of RBCs occurs because renal failure, GI disease (ulcerative col-        The test is not sensitive or specific for
  (laboratory-specific)  their density is greater than plasma.   itis, regional ileitis). For endocarditis,    other conditions.
                       ESR measures the distance in mm that sensitivity = 93%.                               ESR is higher in women, blacks, and
Lavender                erythrocytes fall during 1 hour.       Decreased in: Polycythemia, sickle cell        older persons.
$                                                               anemia, spherocytosis, anisocytosis,         Low value is of no diagnostic
Test must be run                                                hypofibrinogenemia, hypogammaglo-              significance.
  within 2 hours after                                          bulinemia, congestive heart failure,         Am J Med 1985;78:1001.
  sample collection.                                            microcytosis. Drugs: high-dose               Ann Intern Med 1986;104:515.
                                                                corticosteroids.
Erythropoietin, serum Erythropoietin is a glycoprotein hor- Increased in: Anemias associated with            Test is not very useful in differentiat-
(EPO)                  mone produced in the kidney that         bone marrow hyporesponsiveness                ing polycythemia vera from second-
                       induces red blood cell production by (aplastic anemia, iron deficiency ane-             ary polycythemia.
5–20 mIU/mL            stimulating proliferation, differentia- mia), secondary polycythemia (high-           Since virtually all patients with severe




                                                                                                                                                         Erythropoietin
[4–26 IU/L]            tion, and maturation of erythroid        altitude hypoxia, COPD, pulmonary             anemia due to chronic renal failure
                       precursors.                              fibrosis), erythropoietin-producing            respond to EPO therapy, pretherapy
Marbled               Hypoxia is the usual stimulus for         tumors (cerebellar hemangioblastomas,         EPO levels are not indicated.
$$$                    production of EPO.                       pheochromocytomas, renal tumors),            Patient receiving EPO as chronic ther-
                      In conditions of bone marrow hypo-        pregnancy, polycystic kidney disease.         apy should have iron deficiency
                       responsiveness, EPO levels are          Decreased in: Anemia of chronic dis-           screening routinely.
                       elevated.                                ease, renal failure, inflammatory states,     Curr Opin Nephrol Hypertens
                      In chronic renal failure, EPO produc-     primary polycythemia (polycythemia            1994;3:620.
                       tion is decreased.                       vera) (39%).                                 Haematologica 1997;82:406.
Ethanol, serum         Measures serum level of ethyl alcohol Present in: Ethanol ingestion.               Whole blood alcohol concentrations
(EtOH)                  (ethanol).                                                                         are about 15% lower than serum
                                                                                                           concentrations.
0 mg/dL [mmol/L]                                                                                          Each 0.1 mg/dL of ethanol contributes




                                                                                                                                                     Ethanol
                                                                                                           about 22 mosm/kg to serum
Marbled                                                                                                    osmolality.
$$                                                                                                        Legal intoxication in many states is
Do not use alcohol                                                                                         defined as >80 mg/dL (>17 mmol/L).
 swab. Do not remove                                                                                      N Engl J Med 1976;294:757.




                                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
 stopper.
Factor V (Leiden)      The Leiden mutation is a single          Positive in: Hypercoagulability second-   The presence of mutation is only a risk
 mutation               nucleotide base substitution leading     ary to factor V mutation (specificity      factor for thrombosis, not an absolute




                                                                                                                                                     Factor V (Leiden) mutation
Blood                   to an amino acid substitution (gluta-    approaches 100%).                         marker for disease. Homozygotes
                        mine replaces arginine) at one of the                                              have a 50- to 100-fold increase in risk
Lavender or blue        sites where coagulation factor V is                                                of thrombosis (relative to the general
$$$$                    cleaved by activated protein C. The                                                population) and heterozygotes have a
                        mutation causes factor V to be par-                                                7-fold increase in risk. The current
                        tially resistant to protein C, which is                                            PCR and reverse dot blot assay only
                        involved in inhibiting coagulation.                                                detects the Leiden mutation of factor
                        Factor V mutations may be present                                                  V; other mutations may yet be
                        in up to half of the cases of unex-                                                discovered.
                        plained venous thrombosis and are                                                 N Engl J Med 1995;332:912.
                        seen in 95% of patients with acti-                                                Nature 1994;369:64.
                        vated protein C resistance.                                                       Ann Intern Med 1999;130:643.




                                                                                                                                                                                  87
                                                                                                                                                                              88
Test /Range/Collection              Physiologic Basis                           Interpretation                              Comments
Factor VIII assay,     Measures activity of factor VIII (anti- Increased in: Inflammatory states (acute Normal hemostasis requires at least




                                                                                                                                                                              Pocket Guide to Diagnostic Tests
 plasma                 hemophilic factor), a key factor of     phase reactant), last trimester of preg-  25% of factor VIII activity.
                        the intrinsic clotting cascade.         nancy, oral contraceptives.              Symptomatic hemophiliacs usually




                                                                                                                                                          Factor VIII assay
40–150% of normal,                                             Decreased in: Hemophilia A,                have levels ≤5%. Disease levels are
 (varies with age)                                              von Willebrand’s disease, disseminated defined as severe (<1%), moderate
                                                                intravascular coagulation, acquired       (1–5%), and mild (>5%).
Blue                                                            factor VIII antibodies.                  Factor VIII assays are used to guide
$$$                                                                                                       replacement therapy in patients with
Deliver immediately to                                                                                    hemophilia.
 laboratory on ice.                                                                                      Semin Hematol 1967;4:93.
 Stable for 2 hours.
Fecal fat, stool          In healthy people, most dietary fat is   Increased in: Malabsorption from small A random, qualitative fecal fat (so-
Random: <60 droplets       completely absorbed in the small         bowel disease (regional enteritis, celiac called Sudan stain) is only useful if
 of fat/ high power        intestine. Normal small intestinal       disease, tropical sprue), pancreatic in-   positive. Furthermore, it does not cor-
 field                      lining, bile acids, and pancreatic       sufficiency, diarrhea with or without       relate well with quantitative measure-
                           enzymes are required for normal          fat malabsorption.                         ments. Sudan stain appears to detect
72 hour: <7 g/d            fat absorption.                                                                     triglycerides and lipolytic by-products,
                                                                                                               whereas 72-hour fecal fat measures
$$$                                                                                                            fatty acids from a variety of sources,
Qualitative: random                                                                                            including phospholipids, cholesteryl




                                                                                                                                                          Fecal fat
 stool sample is                                                                                               esters, and triglycerides.
 adequate.                                                                                                    The quantitative method can be used to
Quantitative: dietary                                                                                          measure the degree of fat malabsorp-
 fat should be at least                                                                                        tion initially and then after a thera-
 50–150 g/d for 2 days                                                                                         peutic intervention.
 before collection.                                                                                           A normal quantitative stool fat reliably
 Then all stools should                                                                                        rules out pancreatic insufficiency and
 be collected for                                                                                              most forms of generalized small
 72 hours and                                                                                                  intestine disease.
 refrigerated.                                                                                                Gastroenterol Clin North Am 1989;
                                                                                                               18:467.
                                                                                                              Gastroenterology 1992;102:1936.
Fecal occult blood,     Measures blood in the stool using gum Positive in: Upper GI disease (peptic     Although fecal occult blood testing is
 stool                   guaiac as an indicator reagent. In the ulcer, gastritis, variceal bleeding,     an accepted screening test for colon
                         Hemoccult test, gum guaiac is im-      esophageal and gastric cancer), lower    carcinoma, the sensitivity and speci-
Negative                 pregnated in a test paper that is      GI disease (diverticulosis, colonic      ficity of an individual test are low.
$                        smeared with stool using an applica- polyps, colon carcinoma, inflammatory       The utility of fecal occult blood test-
Patient should be on a   tor. Hydrogen peroxide is used as a    bowel disease, vascular ectasias,        ing after digital rectal examination
  special diet free of   developer solution. The resultant      hemorrhoids).                            has not been well studied.
  exogenous peroxidase phenolic oxidation of guaiac in the                                              Three randomized controlled trials




                                                                                                                                                   Fecal occult blood
  activity (meat, fish,   presence of blood in the stool yields                                           have shown reductions in colon can-




                                                                                                                                                                        Common Laboratory Tests: Selection and Interpretation
 turnips, horseradish),  a blue color.                                                                   cer mortality with yearly (33% reduc-
 GI irritants (aspirin,                                                                                  tion) or biennial (15–21% reduction)
 non-steroidal anti-                                                                                     testing. About 1000 fifty-year-olds
 inflammatory drugs),                                                                                     must be screened for 10 years to save
 and iron. To avoid                                                                                      one life.
 false-negatives,                                                                                       BMJ 1998;317:559.
 patients should avoid                                                                                  Ann Intern Med 1997;126:811.
 taking vitamin C.
Patient collects two
 specimens from three
 consecutive bowel
 movements.




                                                                                                                                                                        89
                                                                                                                                                           90
Test /Range/Collection           Physiologic Basis                        Interpretation                             Comments
Ferritin, serum     Ferritin is the body’s major iron stor- Increased in: Iron overload (hemochro- Serum ferritin is clinically useful in




                                                                                                                                                           Pocket Guide to Diagnostic Tests
                     age protein.                             matosis [sensitivity 85%, specificity    distinguishing between iron defi-
Males 16–300 ng/mL The serum ferritin level correlates        95%], hemosiderosis), acute or chronic ciency anemia (serum ferritin levels
 [µg/L]              with total body iron stores.             liver disease, alcoholism, various      diminished) and anemia of chronic
Females 4–161 ng/mL The test is used to detect iron defi-      malignancies (eg, leukemia, Hodgkin’s disease or thalassemia (levels usually
 [µg/L]              ciency, to monitor response to iron      disease), chronic inflammatory disor-    normal or elevated). Test of choice for
                     therapy, and, in iron overload states,   ders (eg, rheumatoid arthritis, adult   diagnosis of iron deficiency anemia.
Marbled              to monitor iron removal therapy. It is Still’s disease), thalassemia minor,
$$                   also used to predict homozygosity        hyperthyroidism, HIV infection, non-                               LR for
                     for hemochromatosis in relatives of      insulin-dependent diabetes mellitus,   Ferritin (ng/mL)       Iron Deficiency
                     affected patients.                       and postpartum state.                        >100                     0.08




                                                                                                                                                Ferritin
                    In the absence of liver disease, it is a Decreased in: Iron deficiency                  45–100                   0.54
                     more sensitive test for iron defi-        (60–75%).                                    35– 45                   1.83
                     ciency than serum iron and iron-                                                      25–35                    2.54
                     binding capacity (transferrin                                                         15–25                    8.83
                     saturation).                                                                           ≤15                   52.0


                                                                                                       Liver disease will increase serum fer-
                                                                                                        ritin levels and mask the diagnosis
                                                                                                        of iron deficiency.
                                                                                                       Am J Hematol 1993;42:177.
                                                                                                       Br J Haematol 1993;85:787.
                                                                                                       J Intern Med 1994;236:315.
                                                                                                       J Gen Intern Med 1992;7:145
 -Fetoprotein, serum   α-Fetoprotein is a glycoprotein pro-   Increased in: Hepatocellular carcinoma The test is not sensitive or specific
(AFP)                   duced both early in fetal life and     (72%), massive hepatic necrosis (74%), enough to be used as a general
                        by some tumors.                        viral hepatitis (34%), chronic active    screening test for hepatocellular car-
0–15 ng/mL [µg/L]                                              hepatitis (29%), cirrhosis (11%),        cinoma. However, screening may be
                                                               regional enteritis (5%), benign gyneco- justified in populations at very high
Marbled                                                        logic diseases (22%), testicular carci-  risk for hepatocellular cancer.
$$                                                             noma (embryonal) (70%),                 In hepatocellular cancer or germ cell
Avoid hemolysis.                                               teratocarcinoma (64%), teratoma          tumors associated with elevated AFP,




                                                                                                                                                 -Fetoprotein
                                                               (37%), ovarian carcinoma (57%),          the test may be helpful in detecting




                                                                                                                                                                   Common Laboratory Tests: Selection and Interpretation
                                                               endometrial cancer (50%), cervical       recurrence after therapy.
                                                               cancer (53%), pancreatic cancer (23%), AFP is also used to screen pregnant
                                                               gastric cancer (18%), colon cancer       women at 15–20 weeks gestation for
                                                               (5%).                                    possible fetal neural tube defects.
                                                              Negative in: Seminoma.                    AFP level in maternal serum or amni-
                                                                                                        otic fluid is compared with levels
                                                                                                        expected at a given gestational age.
                                                                                                       N Engl J Med 1987;317:342.
                                                                                                       Clin Chem 1992;38(8B Part 2):1523.
                                                                                                       West J Med 1993;159:312.
Fibrin D-dimers,       Plasmin acts on fibrin to form various Increased in: Disseminated intravascu- Fibrin D-dimer assay has replaced the
 plasma                 fibrin degradation products. The       lar coagulation (DIC), other thrombotic Fibrin(ogen) Split Products test as a
                        D-dimer level can be used as a mea-   disorders, pulmonary embolism,           screen for DIC, because the D-dimer
Negative                sure of activation of the fibrinolytic venous or arterial thrombosis.           assay can distinguish fibrin degrada-




                                                                                                                                                 Fibrin D-dimers
                        system.                                                                        tion products (in DIC) from fibrino-
Blue                                                                                                   gen degradation products (in primary
$$                                                                                                     fibrinogenolysis).
                                                                                                      Since the presence of fibrin D-dimer is
                                                                                                       not specific for DIC, the definitive
                                                                                                       diagnosis of DIC must depend on
                                                                                                       other tests, including the platelet
                                                                                                       count and serum fibrinogen level.




                                                                                                                                                                   91
                                                                                                      Ann Intern Med 1998;129:1006.
                                                                                                                                                                                                   92
Test /Range/Collection             Physiologic Basis                          Interpretation                               Comments
Fibrinogen               Fibrinogen is synthesized in the liver   Increased in: Inflammatory states (acute    Hypofibrinogenemia is an important




                                                                                                                                                        Fibrinogen (functional)

                                                                                                                                                                                                   Pocket Guide to Diagnostic Tests
 (functional), plasma     and has a half-life of about 4 days.     phase reactant), use of oral contracep-    diagnostic laboratory feature of DIC.
                         Thrombin cleaves fibrinogen to form        tives, pregnancy.                         Diagnosis of dysfibrinogenemia
175– 433 mg/dL            insoluble fibrin monomers, which         Decreased in: Decreased hepatic syn-        depends upon the discrepancy between
[1.75–4.3 g/L]            polymerize to form a clot.               thesis, increased consumption (dissemi-    measurable antigenic and low func-
Panic: <75 mg/dL                                                   nated intravascular coagulation [DIC],     tional (clottable) fibrinogen levels.
                                                                   thrombolysis). Hereditary: Afibrino-       Blood 1982;60:284.
Blue                                                               genemia (rare), hypofibrinogenemia,        Ann Intern Med 1993;118:956.
$$                                                                 dysfibrinogenemia.
Fluorescent trepone-     Detects specific antibodies against    Reactive in: Syphilis: primary (95%),         Used to confirm a reactive nontrepone-
 mal antibody-            Treponema pallidum.                   secondary (100%), late (96%), late            mal screening serologic test for




                                                                                                                                                        Fluorescent treponemal antibody-absorbed
 absorbed, serum         Patient’s serum is first diluted with   latent (100%); also rarely positive in        syphilis such as RPR or VDRL (see
(FTA-ABS)                 nonpathogenic treponemal antigens     collagen-vascular diseases in the             pp 150 and 179, respectively).
                          (to bind nonspecific antibodies). The presence of antinuclear antibody.             Once positive, the FTA-ABS may
Nonreactive               absorbed serum is placed on a slide                                                 remain positive for life. However,
                          that contains fixed T pallidum.                                                      one study found that at 36 months
Marbled                   Fluorescein-labeled antihuman                                                       after treatment, 24% of patients had
$$                        gamma globulin is then added to                                                     nonreactive FTA-ABS tests.
                          bind to and visualize (under a fluo-                                                In a study of HIV-infected men with a
                          rescence microscope) the patient’s                                                  prior history of syphilis, 38% of
                          antibody on treponemes.                                                             patients with AIDS or ARC had loss
                                                                                                              of reactivity to treponemal tests, com-
                                                                                                              pared with 7% of HIV-seropositive
                                                                                                              asymptomatic men and 0% of HIV-
                                                                                                              seronegative men.
                                                                                                             Ann Intern Med 1986;104:368.
                                                                                                             J Infect Dis 1990;162:862.
                                                                                                             Ann Intern Med 1991;114:1005.
Folic acid (RBC),      Folate is a vitamin necessary for       Decreased in: Tissue folate deficiency      Red cell folate level correlates better
 whole blood            methyl group transfer in thymidine      (from dietary folate deficiency), B12       than serum folate level with tissue
                        formation, and hence DNA synthe-        deficiency (50–60%, since cellular          folate deficiency.
165–760 ng/mL           sis. Deficiency can result in mega-      uptake of folate depends on B12).         A low red cell folate level may indicate
[370–1720 nmol/L]       loblastic anemia.                                                                  either folate or B12 deficiency.
                                                                                                          A therapeutic trial of folate (and not
Lavender                                                                                                   red cell or serum folate testing) is




                                                                                                                                                     Folic acid (RBC)
$$$                                                                                                        indicated when the clinical and
                                                                                                           dietary history is strongly suggestive
                                                                                                           of folate deficiency and the peripheral
                                                                                                           smear shows hypersegmented poly-




                                                                                                                                                                                    Common Laboratory Tests: Selection and Interpretation
                                                                                                           morphonuclear leukocytes. However,
                                                                                                           the possibility of vitamin B12 defi-
                                                                                                           ciency must always be considered in
                                                                                                           the setting of megaloblastic anemia,
                                                                                                           since folate therapy will treat the
                                                                                                           hematologic, but not the neurologic,
                                                                                                           sequelae of vitamin B12 deficiency.
                                                                                                          Blood 1983;61:624.
Follicle-stimulating   FSH is stimulated by the hypothala-      Increased in: Primary (ovarian) gonadal Test indicated in the workup of amenor-
 hormone, serum         mic hormone GnRH and is then             failure, ovarian or testicular agenesis,   rhea in women (see Amenorrhea algo-




                                                                                                                                                     Follicle-stimulating hormone
(FSH)                   secreted from the anterior pituitary in castration, postmenopause, Klinefelter’s rithm, p 339), delayed puberty,
                        a pulsatile fashion. Levels rise dur-    syndrome, drugs.                           impotence, and infertility in men.
Male: 1–10 mIU/mL       ing the preovulatory phase of the       Decreased in: Hypothalamic disorders,       Impotence workup should begin with
Female: (mIU/mL)        menstrual cycle and then decline.        pituitary disorders, pregnancy, anorexia serum testosterone measurement. Basal
   Follicular 4–13      Elevation of FSH is the most sensi-      nervosa. Drugs: corticosteroids, oral      FSH levels in premenopausal women
   Luteal 2–13          tive indicator of onset of menopause. contraceptives.                               depend on age, smoking history, and
   Midcycle 5–22                                                                                            menstrual cycle length and regularity.
   Postmenopausal                                                                                         Br Med J 1987;294:815.
    20–138                                                                                                Endocrinol Metab Clin North Am
(laboratory-specific)                                                                                        1992;21:921.
                                                                                                          JAMA 1993;270:83.
Marbled                                                                                                   J Clin Endocrinol Metab 1994; 79:1105.




                                                                                                                                                                                    93
$$
                                                                                                                                                                                                                                   94
Test /Range/Collection             Physiologic Basis                           Interpretation                            Comments




                                                                                                                                                      Free erythrocyte protoporphyrin Fructosamine Gamma-glutamyl transpeptidase
Free erythrocyte pro- Protoporphyrin is produced in the next Increased in: Decreased iron incorpora-        FEP can be used to screen for lead poi-




                                                                                                                                                                                                                                   Pocket Guide to Diagnostic Tests
 toporphyrin, whole    to last step of heme synthesis. In the tion into heme (iron deficiency, infec-         soning in children provided that iron
 blood                 last step, iron is incorporated into   tion, and lead poisoning),                     deficiency has been ruled out.
(FEP)                  protoporphyrin to produce heme.        erythropoietic protoporphyria.                Test does not discriminate between
                       Enzyme deficiencies, lack of iron, or                                                  uroporphyrin, coproporphyrin, and
<35 µg/dL (method-     presence of interfering substances                                                    protoporphyrin, but protoporphyrin is
 dependent)            (lead) can disrupt this process and                                                   the predominant porphyrin measured.
                       cause elevated FEP.                                                                  Clin Pediatr 1991;30:74.
Lavender                                                                                                    Am J Dis Child 1993;147:66.
$$$



Fructosamine, serum      Glycation of albumin produces fruc- Increased in: diabetes mellitus.               Fructosamine correlates well with fast-
                          tosamine, a less expensive marker of                                               ing plasma glucose (r = 0.74) but
1.6–2.6 mmol/L            glycemic control than HbA1c.                                                       cannot be used to predict precisely
                                                                                                             the HbA1c.
Marbled                                                                                                     Acta Diabetologica 1998;35:48.
$
Gamma-glutamyl           GGT is an enzyme present in liver,        Increased in: Liver disease: acute viral GGT is useful in follow-up of alco-
 transpeptidase,           kidney, and pancreas.                    or toxic hepatitis, chronic or subacute     holics undergoing treatment since
 serum                   It is induced by alcohol intake and is     hepatitis, alcoholic hepatitis, cirrhosis,  the test is sensitive to modest
(GGT)                      an extremely sensitive indicator of      biliary tract obstruction (intrahepatic or alcohol intake.
                           liver disease, particularly alcoholic    extrahepatic), primary or metastatic       GGT is elevated in 90% of patients
9–85 U/L                   liver disease.                           liver neoplasm, mononucleosis. Drugs        with liver disease.
[0.15–1.42 µkat/L]                                                  (by enzyme induction): phenytoin, car- GGT is used to confirm hepatic origin
 (laboratory-specific)                                               bamazepine, barbiturates, alcohol.          of elevated serum alkaline
                                                                                                                phosphatase.
Marbled                                                                                                        Alcohol Clin Exp Res 1990;14:250.
$                                                                                                              Am J Gastroenterol 1992;87:991.
Gastrin, serum           Gastrin is secreted from G cells in the Increased in: Gastrinoma (Zollinger-    Gastrin is the first-line test for deter-
                          stomach antrum and stimulates acid      Ellison syndrome) (80–93% sensitiv-     mining whether a patient with active
<300 pg/mL [ng/L]         secretion from the gastric parietal     ity), antral G cell hyperplasia,        ulcer disease has a gastrinoma. Gas-
                          cells.                                  hypochlorhydria, achlorhydria, chronic tric analysis is not indicated.
Marbled                  Values fluctuate throughout the day       atrophic gastritis, pernicious anemia. Before interpreting an elevated level,
$$                        but are lowest in the early morning.    Drugs: antacids, cimetidine, and other  be sure that the patient is not taking




                                                                                                                                                           Gastrin
Overnight fasting                                                 H2 blockers; omeprazole and other pro- antacids, H2 blockers, or proton pump
 required.                                                        ton pump inhibitors.                    inhibitors.
                                                                 Decreased in: Antrectomy with vago-     Both fasting and post-secretin infusion




                                                                                                                                                                     Common Laboratory Tests: Selection and Interpretation
                                                                  tomy.                                   levels may be required for diagnosis.
                                                                                                         Endocrinol Metab Clin North Am
                                                                                                          1993;22:823.
                                                                                                         Lancet 1996;347:270.
Glucose, serum           Normally, the glucose concentration       Increased in: Diabetes mellitus, Cush-      Diagnosis of diabetes mellitus requires a
                          in extracellular fluid is closely regu-    ing’s syndrome (10–15%), chronic pan-       fasting plasma glucose of >126 mg/dL
60–110 mg/dL              lated so that a source of energy is       creatitis (30%). Drugs: corticosteroids,    on more than one occasion.
[3.3–6.1 mmol/L]          readily available to tissues and so       phenytoin, estrogen, thiazides.            Hypoglycemia is defined as a glucose
Panic: <40 or             that no glucose is excreted in the       Decreased in: Pancreatic islet cell dis-     of <50 mg/dL in men and <40 mg/dL
 >500 mg/dL               urine.                                    ease with increased insulin, insulinoma,    in women.




                                                                                                                                                           Glucose
                                                                    adrenocortical insufficiency, hypopitu-     While random serum glucose levels
Marbled                                                             itarism, diffuse liver disease, malig-      correlate with home glucose monitor-
$                                                                   nancy (adrenocortical, stomach,             ing results (weekly mean capillary
Overnight fasting usu-                                              fibrosarcoma), infant of a diabetic          glucose values), there is wide fluctua-
  ally required.                                                    mother, enzyme deficiency diseases           tion within individuals. Thus, glyco-
                                                                    (eg, galactosemia). Drugs: insulin,         sylated hemoglobin levels are favored
                                                                    ethanol, propranolol; sulfonylureas,        to monitor glycemic control.
                                                                    tolbutamide, and other oral hypo-          JAMA 1999;281:1203.
                                                                    glycemic agents.




                                                                                                                                                                     95
                                                                                                                                                                             96
Test /Range/Collection             Physiologic Basis                       Interpretation                              Comments
Glucose tolerance test, The test determines the ability of a   Increased glucose rise (decreased glu- Test is not generally required for diag-




                                                                                                                                                                             Pocket Guide to Diagnostic Tests
 serum                   patient to respond appropriately       cose tolerance) in: Diabetes mellitus,     nosis of diabetes mellitus.
                         to a glucose load.                     impaired glucose tolerance, gestational In screening for gestational diabetes,
Fasting: <110                                                   diabetes, severe liver disease, hyper-     the glucose tolerance test is per-
1-hour: <200                                                    thyroidism, stress (infection), increased formed between 24 and 28 weeks of
2-hour: <140 mg/dL                                              absorption of glucose from GI tract        gestation. After a 50-g oral glucose
[Fasting: <6.4                                                  (hyperthyroidism, gastrectomy,             load, a 2-hour postprandial blood glu-
1-hour: <11.0                                                   gastroenterostomy, vagotomy, excess        cose is measured as a screen. If the
2-hour: <7.7 mmol/L]                                            glucose intake), Cushing’s syndrome,       result is > 140 mg/dL, then the full
                                                                pheochromocytoma. Drugs: diuretics,        test with 100-g glucose load is done




                                                                                                                                                    Glucose tolerance test
Marbled                                                         oral contraceptives, glucocorticoids,      using the following reference ranges:
$$                                                              nicotinic acid, phenytoin.
Subjects should receive                                        Decreased glucose rise (flat glucose                   Fasting: <105
 a 150- to 200-g/d                                              curve) in: Intestinal disease (celiac                1-hour: <190
 carbohydrate diet for                                          sprue, Whipple’s disease), adrenal                   2-hour: <165
 at least 3 days prior to                                       insufficiency (Addison’s disease,                    3-hour: <145 mg/dL
 test. A 75-g glucose                                           hypopituitarism), pancreatic islet
 dose is dissolved in                                           cell tumors or hyperplasia.               Routine screening for gestational dia-
 300 mL of water for                                                                                       betes has not been found to be cost-
 adults (1.75 g/kg for                                                                                     effective, and is not recommended by
 children) and given                                                                                       the Canadian Task Force on the Peri-
 after an overnight                                                                                        odic Health Examination.
 fast. Serial determina-                                                                                  J Fam Pract 1993;37:27.
 tions of plasma or                                                                                       Diabetes Care 1999;22(Suppl 1):55.
 serum venous blood
 glucoses are obtained
 at baseline, at 1 hour,
 and at 2 hours.
Glucose-6-phosphate     G6PD is an enzyme in the hexose          Increased in: Young erythrocytes     In deficient patients, hemolytic anemia
 dehydrogenase           monophosphate shunt that is essen-       (reticulocytosis).                   can be triggered by oxidant agents:
 screen, whole blood     tial in generating reduced glutathione Decreased in: G6PD deficiency.          antimalarial drugs (eg, chloroquine),
(G6PD)                   and NADPH, which protect hemo-                                                nalidixic acid, nitrofurantoin, dap-
                         globin from oxidative denaturation.                                           sone, phenacetin, vitamin C, and
4–8 units/g Hb           Numerous G6PD isoenzymes have                                                 some sulfonamides. Any African-
[0.07–0.14 µkat/L]       been identified.                                                               American about to be given an oxi-
                        Most African-Americans have G6PD-                                              dant drug should be screened for




                                                                                                                                               G6PD screen
Green or blue            A(+) isoenzyme. 10–15% have                                                   G6PD deficiency. (Also screen people




                                                                                                                                                             Common Laboratory Tests: Selection and Interpretation
$$                       G6PD-A(−), which has only 15% of                                              from certain Mediterranean areas:
                         normal enzyme activity. It is transmit-                                       Greece, Italy, etc.)
                         ted in an X-linked recessive manner.                                         Hemolytic episodes can also occur in
                        Some Mediterranean people have the                                             deficient patients who eat fava beans,
                         B– variant that has extremely low                                             in patients with diabetic acidosis,
                         enzyme activity (1% of normal).                                               and in infections.
                                                                                                      G6PD deficiency may be the cause of
                                                                                                       hemolytic disease of newborns in
                                                                                                       Asians and Mediterraneans.
                                                                                                      Ann Intern Med 1985;103:245.
Glutamine, CSF          Glutamine is synthesized in the brain Increased in: Hepatic encephalopathy.   Test is not indicated if albumin, ala-
                         from ammonia and glutamic acid.                                               nine aminotransferase (ALT), biliru-
Glass or plastic tube   Elevated CSF glutamine is associated                                           bin, and alkaline phosphatase are




                                                                                                                                               Glutamine
                         with hepatic encephalopathy.                                                  normal or if there is no clinical
6–15 mg/dL                                                                                             evidence of liver disease.
                                                                                                      Hepatic encephalopathy is essentially
Panic: >40 mg/dL                                                                                       ruled out if the CSF glutamine is
$$$                                                                                                    normal.
                                                                                                      Arch Intern Med 1971;127:1033.
                                                                                                      Science 1974;183:81.




                                                                                                                                                             97
                                                                                                                                                                          98
Test /Range/Collection             Physiologic Basis                         Interpretation                               Comments
Glycohemoglobin;         During the life span of each red blood Increased in: Diabetes mellitus,            Test is not currently recommended for




                                                                                                                                                                          Pocket Guide to Diagnostic Tests
 glycated (glycosy-       cell, glucose combines with hemo-      splenectomy. Falsely high results can       diagnosis of diabetes mellitus, though
 lated) hemoglobin,       globin to produce a stable glycated    occur depending on the method used          it performs well. It is used to monitor
 serum                    hemoglobin.                            and may be due to presence of hemo-         long-term control of blood glucose




                                                                                                                                                        Glycohemoglobin
(HbA1c)                  The level of glycated hemoglobin is     globin F or uremia.                         level.
                          related to the mean plasma glucose    Decreased in: Any condition that short-     Reference ranges are method-specific.
3.9–6.9%                  level during the prior 1–3 months.     ens red cell life span (hemolytic ane-     Development and progression of chro-
 (method-dependent)      There are three glycated A hemoglo-     mias, congenital spherocytosis, acute or    nic complications of diabetes are re-
                          bins, HbA1a HbA1b, and HbA1c.          chronic blood loss, sickle cell disease,    lated to the degree of altered glycemia.
Lavender                  Some assays quantitate HbA1c; some hemoglobinopathies).                            Measurement of HbA1c can improve
$$                        quantitate total HbA1; and some                                                    metabolic control by leading to
                          quantitate all glycated hemoglobins,                                               changes in diabetes treatment.
                          not just A.                                                                       Diabetes Care 1994;17:938.
                                                                                                            JAMA 1996;246:1246.
Growth hormone,      Growth hormone is a single-chain      Increased in: Acromegaly (90% have    Nonsuppressibility of GH levels to
 serum                polypeptide of 191 amino acids that   GH levels >10 ng/mL), Laron dwarfism <2 ng/mL after 100 g oral glucose
(GH)                  induces the generation of             (defective GH receptor), starvation.  and elevation of IGF-1 levels are the
                      somatomedins, which directly stimu- Drugs: dopamine, levodopa.              two most sensitive tests for acrome-
0–5 ng/mL [µg/L]      late collagen and protein synthesis. Decreased in: Pituitary dwarfism,       galy. Random determinations of GH
                     GH levels are subject to wide fluctua- hypopituitarism.                       are rarely useful in the diagnosis of




                                                                                                                                               Growth hormone
Marbled               tions during the day.                                                       acromegaly.
$$$                                                                                              For the diagnosis of hypopituitarism or
                                                                                                  growth hormone deficiency in chil-




                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
                                                                                                  dren, an insulin hypoglycemia test
                                                                                                  has been used. Failure to increase
                                                                                                  GH levels to > 5 ng/mL after insulin
                                                                                                  (0.1 unit/kg) is consistent with
                                                                                                  GH deficiency.
                                                                                                 Endocrinol Metab Clin North Am
                                                                                                  1992;21:649.
                                                                                                 Clin Endocrinol 1997;46:531.
                                                                                                 Lancet 1998;352:1455.
Haptoglobin, serum   Haptoglobin is a glycoprotein synthe- Increased in: Acute and chronic infec- Low haptoglobin is considered an indi-
                      sized in the liver that binds free    tion (acute phase reactant), malignancy, cator of hemolysis, but it is of uncer-
46–316 mg/dL          hemoglobin.                           biliary obstruction, ulcerative colitis,  tain clinical predictive value because
[0.5–2.2 g/L]                                               myocardial infarction, and diabetes       of the greater prevalence of other




                                                                                                                                               Haptoglobin
                                                            mellitus.                                 conditions associated with low levels
Marbled                                                    Decreased in: Newborns and children,       and because of occasional normal
$$                                                          posttransfusion intravascular hemoly-     individuals who have very low levels.
                                                            sis, autoimmune hemolytic anemia,         It thus has low specificity.
                                                            liver disease (10%). May be decreased High-normal levels probably rule out
                                                            following uneventful transfusion (10%) significant intravascular hemolysis.
                                                            for unknown reasons.                     JAMA 1980;243:1909.
                                                                                                     Clin Chem 1987;33:1265.




                                                                                                                                                                99
                                                                                                                                                                                         100
Test /Range/Collection             Physiologic Basis                           Interpretation                               Comments
Helicobacter pylori      Helicobacter pylori is a gram-negative Increased (positive) in: Histologic        95% of patients with duodenal ulcers
                          spiral bacterium that is found on gas- (chronic or chronic active) gastritis due and > 70% of patients with gastric




                                                                                                                                                                                         Pocket Guide to Diagnostic Tests
 antibody, serum
                          tric mucosa. It induces acute and      to H pylori infection (with or without     ulcers have chronic infection with
Negative                  chronic inflammation in the gastric     peptic ulcer disease). Sensitivity 98%,    H pylori along with associated histo-
                          mucosa and a positive serologic anti- specificity 48%. Asymptomatic adults:        logic gastritis. All patients with peptic
Marbled                   body response. Serologic testing for   15–50%.                                    ulcer disease and positive H pylori
$$                        H pylori antibody (IgG) is by                                                     serology should be treated to eradi-
                          ELISA.                                                                            cate H pylori infection.
                                                                                                           The prevalence of H pylori-positive
                                                                                                            serologic tests in asymptomatic adults




                                                                                                                                                          Helicobacter pylori antibody
                                                                                                            is approximately 35% overall but is
                                                                                                            >50% in patients over age 60. Fewer
                                                                                                            than one in six adults with H pylori
                                                                                                            antibody develop peptic ulcer disease.
                                                                                                            Treatment of asymptomatic adults is
                                                                                                            not currently recommended.
                                                                                                           The role of H pylori in patients with
                                                                                                            chronic dyspepsia is controversial.
                                                                                                            There is currently no role for treatment
                                                                                                            of such patients except in clinical trials.
                                                                                                           After successful eradication, serologic
                                                                                                            titers fall over a 3- to 6-month period
                                                                                                            but remain positive in up to 50% of
                                                                                                            patients at 1 year.
                                                                                                           Gastroenterol Clin North Am
                                                                                                            1993;22:105.
                                                                                                           Gut 1994;35:19.
                                                                                                           Ann Intern Med 1994;120:977.
                                                                                                           JAMA 1994;272:65.
                                                                                                           Can J Infect Dis 1998;9:277.
Hematocrit, whole   The hematocrit represents the percent- Increased in: Hemoconcentration (as in Conversion from hemoglobin (Hb) to
 blood               age of whole blood volume com-         dehydration, burns, vomiting), poly-   hematocrit is roughly Hb × 3 = Hct.
(Hct)                posed of erythrocytes.                 cythemia, extreme physical exercise.  Hematocrit reported by clinical labora-
                    Laboratory instruments calculate the Decreased in: Macrocytic anemia (liver tories is not a spun hematocrit. The
Male: 39–49%         Hct from the erythrocyte count         disease, hypothyroidism, vitamin B12   spun hematocrit may be spuriously
Female: 35–45%       (RBC) and the mean corpuscular         deficiency, folate deficiency), normo-   high if the centrifuge is not calibra-
(age-dependent)      volume (MCV) by the formula:           cytic anemia (early iron deficiency,    ted, if the specimen is not spun to




                                                                                                                                             Hematocrit
                                                            anemia of chronic disease, hemolytic   constant volume, or if there is
                             Hct = RBC × MCV




                                                                                                                                                            Common Laboratory Tests: Selection and Interpretation
Lavender                                                    anemia, acute hemorrhage) and micro-   “trapped plasma.”
$                                                           cytic anemia (iron deficiency, thal-   In determining transfusion need, the
                                                            assemia).                              clinical picture must be considered
                                                                                                   in addition to the hematocrit.
                                                                                                  Point-of-care instruments may not
                                                                                                   measure hematocrit accurately in
                                                                                                   all patients.
                                                                                                  JAMA 1988;259:2433.
                                                                                                  Arch Pathol Lab Med 1994;118:429.
                                                                                                  Clin Chem 1995;41:306.
Hemoglobin A2,      HbA2 is a minor component of normal Increased in: β-Thalassemia major       Test is useful in the diagnosis of
 whole blood         adult hemoglobin (< 3.5% of         (HbA2 levels 4–10% of total Hb),        β-thalassemia minor (in absence of
(HbA2)               total Hb).                          β-thalassemia minor (HbA2 levels        iron deficiency, which decreases
                                                         4–8% of total Hb).                      HbA2 and can mask the diagnosis).




                                                                                                                                            Hemoglobin A2
1.5–3.5% of total                                       Decreased in: Untreated iron deficiency, Quantitated by column chromatographic
 hemoglobin (Hb)                                         hemoglobin H disease.                   or automated HPLC techniques.
                                                                                                Normal HbA2 levels are seen in delta
Lavender                                                                                         β-thalassemia or very mild
$$                                                                                               β-thalassemias.
                                                                                                Blood 1988;72:1107.
                                                                                                J Clin Pathol 1993;46:852.
                                                                                                Hematol Pathol 1994;8:25.




                                                                                                                                                            101
                                                                                                                                                                                 102
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Hemoglobin elec-         Hemoglobin electrophoresis is used as ↑HbS: HbA > HbS = Sickle cell trait       Evaluation of a suspected hemoglo-
                                                                   (HbAS) or sickle α-thalassemia; HbS




                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
 trophoresis, whole       a screening test. It is used to detect                                          binopathy should include electro-




                                                                                                                                                    Hemoglobin electrophoresis
 blood                    and differentiate hemoglobin vari-       and F, no HbA = Sickle cell anemia     phoresis of a hemolysate to detect an
                          ants.                                    (HbSS) or sickle β-thalassemia; HbS > abnormal hemoglobin and quantita-
HbA: > 95                Separation of hemoglobins by elec-        HbA and F: Sickle β+-thalassemia.      tion of hemoglobins A2 and F.
HbA2: 1.5–3.5%            trophoresis is based on different rates ↑HbC: HbA > HbC = HbC trait (HbAC); Automated HPLC instruments are prov-
                          of migration of charged hemoglobin       HbC and F, no HbA = HbC disease;       ing to be useful alternative methods
Lavender, blue, or        molecules in an electric field.           HbC > HbA = HbC β+-thalassemia.        for hemoglobinopathy screening. Mol-
 green                                                            ↑HbH: HbH disease.                      ecular diagnosis aids in genetic coun-
$$                                                                ↑HbA2, F: See HbA2, above, and HbF,     seling of patients with thalassemia and
                                                                   below.                                 combined hemoglobinopathies.
                                                                                                         Semin Perinatol 1990;14:483.
                                                                                                         Clin Chem 1990;36:903.
Hemoglobin, fetal,       Fetal hemoglobin constitutes about    Increased in: Hereditary disorders: eg, Semiquantitative acid elution test pro-
 whole blood              75% of total hemoglobin at birth and β-thalassemia major (60–100% of total vides an estimate of fetal hemoglobin
(HbF)                     declines to 50% at 6 weeks, 5% at     Hb is HbF), β-thalassemia minor         only and varies widely between labora-
                          6 months, and <1.5% by 1 year. Dur- (2–5% HbF), sickle cell anemia            tories. It is useful in distinguishing
Adult: <2%                ing the first year, adult hemoglobin   (1–3% HbF), hereditary persistence of   hereditary persistence of fetal hemoglo-
 (varies with age)        (HbA) becomes the predominant         fetal hemoglobin (10–40% HbF).          bin (all RBCs show an increase in fetal
                          hemoglobin.                           Acquired disorders <10% HbF):           hemoglobin) from β-thalassemia minor




                                                                                                                                                   Hemoglobin, fetal
Lavender, blue,                                                 aplastic anemia, megaloblastic          (only a portion of RBCs are affected).
 or green                                                       anemia, leukemia.                      Enzyme-linked antiglobulin test is used




                                                                                                                                                                       Common Laboratory Tests: Selection and Interpretation
$$                                                             Decreased in: Hemolytic anemia of the    to detect fetal red cells in the Rh(–)
                                                                newborn.                                maternal circulation in suspected
                                                                                                        cases of Rh sensitization and to deter-
                                                                                                        mine the amount of RhoGAM to
                                                                                                        administer (1 vial/15 mL fetal RBC).
                                                                                                       Prenatal diagnosis of hemoglobino-
                                                                                                        pathies may be accomplished by quan-
                                                                                                        titative hemoglobin levels by HPLC or
                                                                                                        molecular diagnostic techniques.
                                                                                                       J Clin Pathol 1972;25:738.
                                                                                                       Clin Chem 1992;38:1906.
Hemoglobin, total,     Hemoglobin is the major protein of        Increased in: Hemoconcentration (as in Hypertriglyceridemia and very high
 whole blood             erythrocytes and transports oxygen       dehydration, burns, vomiting), poly-   white blood cell counts can cause
(Hb)                     from the lungs to peripheral tissues.    cythemia, extreme physical exercise.   false elevations of Hb.
                       It is measured by spectrophotometry       Decreased in: Macrocytic anemia (liver JAMA 1988;259:2433.




                                                                                                                                                   Hemoglobin, total
Male: 13.6–17.5          on automated instruments after           disease, hypothyroidism, vitamin B12
Female: 12.0–15.5 g/dL hemolysis of red cells and con-            deficiency, folate deficiency), normo-
 (age-dependent)         version of all hemoglobin to             cytic anemia (early iron deficiency,
[Male: 136–175           cyanmethemoglobin.                       anemia of chronic disease, hemolytic
Female: 120–155 g/L]                                              anemia, acute hemorrhage), and
Panic: ≤7 g/dL                                                    microcytic anemia (iron deficiency,
                                                                  thalassemia).




                                                                                                                                                                       103
Lavender
$
                                                                                                                                                                         104
Test /Range/Collection            Physiologic Basis                        Interpretation                            Comments
Hemosiderin, urine    Hemosiderin is a protein produced by Increased in: Intravascular hemolysis: Hemosiderin can be qualitatively




                                                                                                                                                                         Pocket Guide to Diagnostic Tests
                       the digestion of hemoglobin. Its      hemolytic transfusion reactions, parox- detected in urinary sediment using
Negative               presence in the urine indicates acute ysmal nocturnal hemoglobinuria,            Prussian blue stain.




                                                                                                                                                  Hemosiderin
                       or chronic release of free hemoglo-   microangiopathic hemolytic anemia,        Med Clin North Am 1992;76:649.
Urine container        bin into the circulation with accom-  mechanical destruction of erythrocytes
$$                     panying depletion of the scavenging   (heart valve hemolysis), sickle cell ane-
Fresh, random sample. proteins, hemopexin and haptoglo-      mia, thalassemia major, oxidant drugs
                       bin. Presence of hemosiderin usually with G6PD deficiency (eg, dapsone).
                       indicates intravascular hemolysis or  Hemochromatosis.
                       recent transfusion.
Hepatitis A antibody, Hepatitis A is caused by a non-          Positive in: Acute hepatitis A (IgM),    The most commonly used test for
 serum                 enveloped 27 nm RNA virus of the         convalescence from hepatitis A (IgG).    hepatitis A antibody is an immuno-
(Anti-HAV)             enterovirus-picornavirus group and                                                assay that detects total IgG and IgM




                                                                                                                                                  Hepatitis A antibody
                       is usually acquired by the fecal-oral                                             antibodies. This test can be used to
Negative               route. IgM antibody is detectable                                                 establish immune status. Specific IgM
                       within a week after symptoms                                                      testing is necessary to diagnose acute
Marbled                develop and persists for 6 months.                                                hepatitis A.
$$                     IgG appears 4 weeks later than IgM                                               IgG antibody positivity is found in
                       and persists for years (see Figure                                                40–50% of adults in USA and Europe
                       8–7, p 343, for time course of sero-                                              (higher rates in developing nations).
                       logic changes).                                                                  Testing for anti-HAV (IgG) may reduce
                                                                                                         cost of HAV vaccination programs.
                                                                                                        Arch Intern Med 1994;154:663.
Hepatitis B surface     In hepatitis B virus infection, surface Increased in: Acute hepatitis B, chronic First-line test for the diagnosis of acute




                                                                                                                                                       Hepatitis B surface antigen Hepatitis B surface antibody Hepatitis B core antibody
 antigen, serum          antigen is detectable 2–5 weeks         hepatitis B (persistence of HBsAg for      or chronic hepatitis B. If positive, no
(HBsAg)                  before onset of symptoms, rises in      >6 months, positive HBcAb [total]),        other test is needed.
                         titer, and peaks at about the time of   HBsAg-positive carriers.                  HBeAg is a marker of extensive viral re-
Negative                 onset of clinical illness.             May be undetectable in acute hepatitis B plication found only in HBsAg-positive
                        Generally it persists for 1–5 months,    infection. If clinical suspicion is high,  sera. Persistently HBeAg-positive
Marbled                  declining in titer and disappearing     HBcAb (IgM) test is then indicated.        patients are more infectious than
$$                       with resolution of clinical symptoms                                               HBeAg-negative patients and more
                         (see Figure 8–8, p 344, for time                                                   likely to develop chronic liver disease.




                                                                                                                                                                                                                                            Common Laboratory Tests: Selection and Interpretation
                         course of serologic changes).                                                     Annu Rev Med 1981;32:1.
                                                                                                           Clin Microbiol Rev 1999;12:351.
Hepatitis B surface     Test detects antibodies to hepatitis B Increased in: Hepatitis B immunity due       Test indicates immune status. It is not
 antibody, serum         virus (HBV) which are thought to        to HBV infection or hepatitis B vacci-      useful for the evaluation of acute or
(HBsAb, anti-HBs)        confer immunity to hepatitis B.         nation.                                     chronic hepatitis.
                         Since several subtypes of hepatitis B Absent in: Hepatitis B carrier state, non-   (See Figure 8–8, p 344, for time course
Negative                 exist, there is a possibility of subse- exposure.                                   of serologic changes.)
                         quent infection with a second sub-                                                 Ann Intern Med 1985;103:201.
Marbled                  type.                                                                              Dig Dis Scie 1986;31:620
$$                                                                                                          Clin Microbiol Rev 1999;12:351.



Hepatitis B core anti- HBcAB (IgG and IgM) will be posi- Positive in: Hepatitis B (acute and chro- HBcAb (total) is useful in evaluation
 body, total, serum     tive (as IgM) about 2 months after      nic), hepatitis B carriers (high levels),  of acute or chronic hepatitis only if
(HBcAb, anti-HBc)       exposure to hepatitis B. Its persistent prior hepatitis B (immune) when IgG        HBsAg is negative. An HBcAb (IgM)
                        positivity may reflect chronic hepati- present in low titer with or without         test is then indicated only if the
Negative                tis (IgM) or recovery (IgG). (See       HBsAb.                                     HBcAb (total) is positive.
                        Figure 8–8, p 344, for time course of Negative: After hepatitis B vaccination. HBcAb (IgM) may be the only serologic
Marbled                 serologic changes.)                                                                indication of acute HBV infection.
$$                                                                                                        Dig Dis Sci 1985;30:1022.
                                                                                                          Mayo Clin Proc 1988;63:201.




                                                                                                                                                                                                                                            105
                                                                                                          Clin Microbiol Rev 1999;12:351.
                                                                                                                                                                         106
Test /Range/Collection            Physiologic Basis                         Interpretation                         Comments
Hepatitis Be             HBeAg is a soluble protein secreted by Increased (positive) in: HBV         The assumption has been that loss of




                                                                                                                                                                         Pocket Guide to Diagnostic Tests
 antigen/antibody         hepatitis B virus, related to HBcAg,    (acute, chronic) hepatitis.         HBeAg and accumulation of HBeAb
 (HBeAg/Ab), serum        indicating viral replication and infec-                                     are associated with decreased infec-
                          tivity. Two distinct serologic types of                                     tivity. Testing has proved unreliable,




                                                                                                                                                  Hepatitis Be antigen
Negative                  hepatitis B have been described, one                                        and tests are not routinely needed as
                          with a positive HBeAg and the other                                         indicators of infectivity. All patients
Marbled                   with a negative HBeAg and a posi-                                           positive for HBsAg must be consid-
$$                        tive anti-HBe antibody.                                                     ered infectious.
                                                                                                     Anti-HBeAb is used to select patients
                                                                                                      for clinical trials of interferon therapy
                                                                                                      or liver transplantation.
                                                                                                     Proc Natl Acad Sci U S A
                                                                                                      1991;88:4186.
                                                                                                     J Med Microbiol 1994;41:374.
Hepatitis C antibody, Detects antibody to hepatitis C virus. Increased in: Acute hepatitis C (only   Sensitivity of current assays is 86%,
 serum                Current screening test (ELISA)          20–50%; seroconversion may take         specificity 99.5%.
(HCAb)                 detects antibodies to proteins         6 months or more), posttransfusion     Seropositivity for hepatitis C docu-
                       expressed by putative structural       chronic non-A, non-B hepatitis          ments previous exposure, not
Negative               (HC34) and nonstructural (HC31,        (70–90%), sporadic chronic non-A,       necessarily acute infection.




                                                                                                                                                  Hepatitis C antibody
                       C100-3) regions of the HCV             non-B hepatitis (30–80%), blood        Seronegativity in acute hepatitis does
Marbled                genome. The presence of these anti-    donors (0.5–1%), non-blood-donating     not exclude the diagnosis of hepatitis
$$                     bodies indicates that the patient has  general public (2–3%), hemophiliacs     C, especially in immunosuppressed
                       been infected with HCV, may harbor (75%), intravenous drug abusers             patients.
                       infectious HCV, and may be capable (40–80%), hemodialysis patients            Testing of donor blood for hepatitis C
                       of transmitting HCV.                   (1–30%), male homosexuals (4%).         has significantly reduced the inci-
                      A recombinant immunoblot assay                                                  dence of posttransfusion hepatitis.
                       (RIBA) is available as a confirma-                                             N Engl J Med 1989;321:1538.
                       tory test.                                                                    Hepatology 1993;18:497.
                                                                                                     Dis Mon 1994;40(3):117.
                                                                                                     Am Fam Physician 1999;59:79.
Hepatitis D antibody, This antibody is a marker for acute or Positive in: Hepatitis D.                   Test only indicated in HBsAg-positive
 serum                 persisting infection with the delta                                                patients. Chronic HDV hepatitis
(Anti-HDV)             agent, a defective RNA virus that                                                  occurs in 80–90% of HBsAg carriers




                                                                                                                                                  Hepatitis D antibody
                       can only infect HBsAg-positive                                                     who are superinfected with delta, but
Negative               patients.                                                                          in less than 5% of those who are co-
                      Hepatitis B virus (HBV) plus hepatitis                                              infected with both viruses
Marbled                D virus (HDV) infection may be                                                     simultaneously.
$$                     more severe than HBV infection                                                    Hepatology 1985;5:188.




                                                                                                                                                                              Common Laboratory Tests: Selection and Interpretation
                       alone. Antibody to HDV ordinarily                                                 Ann Intern Med 1989;110:779.
                       persists for about 6 months following
                       acute infection. Further persistence
                       indicates carrier status.
Heterophile aggluti-    Infectious mononucleosis is an acute Positive in: Infectious mononucleosis      The three classic signs of infectious
 nation, serum           saliva-transmitted infectious disease (90–95%).                                  mononucleosis are lymphocytosis, a
(Monospot,               due to the Epstein-Barr virus (EBV). Negative in: Heterophile-negative           “significant number” (>10–20%) of
 Paul-Bunnell test)     Heterophile (Paul-Bunnell) antibodies mononucleosis: CMV, heterophile-            atypical lymphocytes on Wright-
                         (IgM) appear in 60% of mononucle-     negative EBV, toxoplasmosis, hepatitis stained peripheral blood smear, and




                                                                                                                                                  Heterophile agglutination
Negative                 osis patients within 1–2 weeks and in viruses, HIV-1 seroconversion, listerio- positive heterophile test.
                         80–90% within the first month. They sis, tularemia, brucellosis, cat scratch    If heterophile test is negative in the
Marbled                  are not specific for EBV but are       disease, Lyme disease, syphilis, rick-     setting of hematologic and clinical
$                        found only rarely in other disorders. ettsial infections, medications            evidence of illness, a repeat test in
                        Titers are substantially diminished by (phenytoin, sulfasalazine, dapsone),       1–2 weeks may be positive. EBV
                         3 months after primary infection and collagen-vascular diseases (especially      serology (anti-VCA and anti-EBNA)
                         are not detectable by 6 months.       lupus), subacute infective endocarditis. may also be indicated, especially in
                                                                                                          children and teenage patients who
                                                                                                          may have negative heterophile tests
                                                                                                          (see EBV antibodies, p 85).
                                                                                                        Hum Pathol 1974;5:551.
                                                                                                        Pediatrics 1985;75:1011.
                                                                                                        Clin Microbiol Rev 1988;1:300.




                                                                                                                                                                              107
                                                                                                                                                                                108
Test /Range/Collection           Physiologic Basis                        Interpretation                            Comments
Histoplasma capsula-    Heat-stable H capsulatum polysaccha- Increased in: Disseminated histoplas-    RIA for H capsulatum var capsulatum




                                                                                                                                                                                Pocket Guide to Diagnostic Tests
 tum antigen, urine,     ride is detected by radioimmuno-     mosis (90–97% in urine, 50–78% in        polysaccharide antigen in urine is a
 serum, CSF              assay or ELISA using alkaline        blood, and approximately 42% in CSF), useful test in diagnosis of dissemi-
(HPA)                    phosphatase or horseradish           localized disease (16% in urine), blas-  nated histoplasmosis and in assessing




                                                                                                                                               Histoplasma capsulatum antigen
                         peroxidase-conjugated antibodies.    tomycosis (urine and serum), coccid-     efficacy of treatment or in detecting
Negative                                                      ioidomycosis (CSF).                      relapse, especially in AIDS patients
                                                                                                       and when serologic tests for antibod-
Marbled (serum)                                                                                        ies may be negative. Because the test
                                                                                                       has low sensitivity in localized pul-
$$                                                                                                     monary disease, it is not useful for
Deliver urine, CSF in a                                                                                ruling out localized pulmonary histo-
 clean plastic or glass                                                                                plasmosis. HPA in bronchoalveolar
 container tube.                                                                                       lavage fluid has 70% sensitivity for
                                                                                                       the diagnosis of pulmonary
                                                                                                       histoplasmosis.
                                                                                                      N Engl J Med 1986;314:83.
                                                                                                      Am J Med 1989;87:396.
                                                                                                      Arch Intern Med 1989;149:302.
                                                                                                      Am Rev Respir Dis 1992;145:1421.
Histoplasma capsula-    Histoplasmosis is the most common        Positive in: Previous, chronic, or acute Histoplasmosis is usually seen in the




                                                                                                                                                       Histoplasma capsulatum precipitins
 tum precipitins,        systemic fungal infection and typi-      histoplasma infection, recent histoplas- Mississippi and Ohio River Valleys
 serum                   cally starts as a pulmonary infection    min skin testing. Cross-reactions at low but may appear elsewhere.
                         with influenza-like symptoms. This        levels in patients with blastomycosis    Test is useful as a screening test or as
Negative                 may heal, progress, or lie dormant       and coccidioidomycosis.                   an adjunct to complement fixation
                         with reinfection occurring at a later                                              test (see below) in diagnosis of sys-
Marbled                  time.                                                                              temic histoplasmosis.
$$                      This test screens for presence of histo-                                           Rose NR et al (editors): Manual of




                                                                                                                                                                                            Common Laboratory Tests: Selection and Interpretation
                         plasma antibody by detecting precip-                                               Clinical Laboratory Immunology,
                         itin “H” and “M” bands.                                                            4th ed. American Society for Micro-
                        Positive H band indicates active infec-                                             biology, 1992.
                         tion, M band indicates acute or
                         chronic infection or prior skin test-
                         ing. Presence of both suggests active
                         histoplasmosis.
Histoplasma capsula- Quantitates level of histoplasma          Increased in: Previous, chronic, or          Elevated CF titers of >1 16 are sug-




                                                                                                                                                       Histoplasma capsulatum CF antibody
 tum complement fix- antibody.                                   acute histoplasma infection (75–80%),        gestive of infection. Titers of >1 32
 ation (CF) antibody, Antibodies in primary pulmonary           recent histoplasmin skin testing (20%),      or rising titers are usually indicative
 serum                   infections are generally found within  other fungal disease, leishmaniasis.         of active infection.
                         4 weeks after exposure and frequently Cross-reactions in patients with blas-       Histoplasmin skin test is not recom-
<1 4 titer               are present at the time symptoms       tomycosis and coccidioidomycosis.            mended for diagnosis since it inter-
                         appear.                                                                             feres with subsequent serologic tests.
Marbled                 Two types of CF test are available                                                  About 3.5–12% of clinically normal
$$                       based on mycelial antigen and yeast                                                 persons have positive titers, usually
Submit paired sera, one phase antigen. The yeast phase test is                                               less than 1 16.
 specimen collected      considerably more sensitive.                                                       Hosp Pract (Off Ed) Feb 1991;26:41.
 within 1 week after    Latex agglutination (LA) and ELISA                                                  Rose NR et al (editors): Manual of
 onset of illness and    tests are also available but are less                                               Clinical Laboratory Immunology,
 another 2 weeks later. reliable.                                                                            4th ed. American Society for Micro-
                                                                                                             biology, 1992.




                                                                                                                                                                                            109
                                                                                                                                                                    110
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
HIV antibody, serum      This test detects antibody against the Positive in: HIV infection: EIA sensitiv- A positive p24 antigen test in an HIV
                                                                 ity >99% after first 2–4 months of




                                                                                                                                                                    Pocket Guide to Diagnostic Tests
                          human immunodeficiency virus-1                                                    antibody-negative individual must be
Negative                  (HIV-1), the etiologic agent of AIDS. infection, specificity 99%. When com-       confirmed by a viral neutralization
                         HIV antibody test is considered posi-   bined with confirmatory test, specificity assay.
Marbled                   tive only when a repeatedly reactive   is 99.995%.                              While Western blot test is currently the




                                                                                                                                                     HIV antibody
$$                        enzyme immunoassay (EIA) is con-                                                 most sensitive and specific assay for
                          firmed by a Western blot analysis                                                 HIV serodiagnosis, it is highly depen-
                          or immunofluorescent antibody                                                     dent on the proficiency of the labora-
                          test (IFA).                                                                      tory performing the test and on the
                                                                                                           standardization of the procedure.
                                                                                                          Ann Intern Med 1987;106:671.
                                                                                                          Arch Pathol Lab Med 1989;113:975.
                                                                                                          JAMA 1991;266:2861.
                                                                                                          Infect Dis Clin North Am 1993;7:203.
HLA typing, serum       The human leukocyte antigen (HLA) Useful in: Evaluation of transplant can-         While diseases associated with particu-
 and blood               system consists of four closely      didates and potential donors and for          lar HLA antigens have been identi-
(HLA)                    linked loci (HLA-A, -B, -C, and      paternity and forensic testing.               fied, HLA typing for the diagnosis
                         -DR) located on the short arm of                                                   of these diseases is not generally
Marbled (2 mL) and       chromosome 6.                                                                      indicated.




                                                                                                                                                     HLA typing
 Yellow (40 mL)         The most widely used technique for                                                 Cell 1984;36:1.
$$$$                     HLA typing is the microlymphocyte
Specimens must be <      toxicity test. This is a complement-
 24 hours old. Refrig-   mediated serologic assay in which
 erate serum, but not    antiserum containing specific anti-
 blood in yellow tubes. HLA antibodies is added to periph-
                         eral blood lymphocytes. Cell death
                         indicates that the lymphocytes car-
                         ried the specific targeted antigen.
HLA-B27 typing,         The HLA-B27 allele is found in         There is an increased incidence of spon-   The best diagnostic test for ankylosing
 whole blood             approximately 8% of the US white       dyloarthritis among patients who are       spondylitis is a lumbar spine film and




                                                                                                                                                      HLA-B27 typing
                         population. It occurs less frequently  HLA-B27-positive. HLA-B27 is pre-          not HLA-B27 typing.
Negative                 in the African-American population. sent in 88% of patients with ankylosing      HLA-B27 testing is not usually clini-
                                                                spondylitis. It is also associated with    cally indicated.
Yellow                                                          the development of Reiter’s syndrome      Ann Intern Med 1980;92:208.
$$$                                                             (80%) following infection with            Br J Rheumatol 1987;36:185.
Specimens must be                                               Shigella or Salmonella.
 <24 hours old.




                                                                                                                                                                                   Common Laboratory Tests: Selection and Interpretation
5-Hydroxy-              Serotonin (5-hydroxytryptamine) is a Increased in: Metastatic carcinoid           Since most carcinoid tumors drain into
 indoleacetic acid,      neurotransmitter that is metabolized  tumor (foregut, midgut, and bronchial).     the portal vein and serotonin is
 urine                   by monoamine oxidase (MAO) to         Nontropical sprue (slight increase).        rapidly cleared by the liver, the carci-




                                                                                                                                                      5-Hydroxyindoleacetic acid
(5-HIAA)                 5-HIAA and then excreted into the     Diet of bananas, walnuts, avocado,          noid syndrome (flushing, bronchial
                         urine.                                eggplant, pineapple, plums. Drugs:          constriction, diarrhea, hypotension,
2–8 mg/24 h             Serotonin is secreted by most carci-   reserpine.                                  and cardiac valvular lesions) is a late
[10– 40 µmol/d]          noid tumors, which arise from neuro- Negative in: Rectal carcinoids (usually),    manifestation of carcinoid tumors,
                         endocrine cells in locations derived  renal insufficiency. Drugs: MAO              appearing only after hepatic metasta-
Urine bottle containing from the embryonic gut.                inhibitors, phenothiazines.                 sis has occurred.
 hydrochloric acid                                            Test is often falsely positive because      N Engl J Med 1986;315:702.
$$                                                             pretest probability is low. Using          Clin Chem 1992;38:1730.
                                                               5-HIAA/Cr ratio may improve                Endocrinol Metab Clin North Am
                                                               performance.                                1993;22:823.
                                                                                                          Clin Chem 1994;40:86.
                                                                                                          Ann Clin Lab Sci 1998;28:167.




                                                                                                                                                                                   111
                                                                                                                                                                        112
Test /Range/Collection             Physiologic Basis                        Interpretation                           Comments
IgG index, serum and      This test compares CSF IgG and albu- Increased in: Multiple sclerosis         Test is reasonably sensitive but not




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
 CSF                       min levels to serum levels.          (80–90%), neurosyphilis, subacute scle- specific for multiple sclerosis. (Com-
                          An increased ratio allegedly reflects  rosing panencephalitis, other inflamma- pare with Oligoclonal bands, p 131.)
0.29–0.59 ratio            synthesis of IgG within the central  tory and infectious CNS diseases.       Mayo Clin Proc 1989;64:577.




                                                                                                                                                IgG index
                           nervous system.                                                              J Clin Pathol 1996;49:24.
Marbled (for serum)
 and glass/plastic tube
 (for CSF)
$$$
Collect serum and CSF
 simultaneously.
Immunoelectrophore- Immunoelectrophoresis is used to        Positive in: Presence of identifiable Test is indicated to identify an Ig spike
  sis, serum         identify specific immunoglobulin         monoclonal paraprotein: multiple     seen on serum protein electrophore-
(IEP)                (Ig) classes. Serum is separated elec- myeloma, Waldenström’s macroglobu- sis, to differentiate a polyclonal from




                                                                                                                                                Immunoelectrophoresis
                     trophoretically and reacted with anti- linemia, Franklin’s disease (heavy    a monoclonal increase, and to identify
Negative             sera of known specificity. Newer         chain disease), lymphoma, leukemia,  the nature of a monoclonal increase.
                     technique (immunofixation) is            monoclonal gammopathy of undeter-   Test is not quantitative and is not sen-
Marbled              available and easier to interpret.      mined significance.                   sitive enough to use for the evaluation
$$$                                                         The most common form of myeloma is    of immunodeficiency. Order quantita-
                                                             the IgG type.                        tive immunoglobulins for this pur-
                                                                                                  pose (see below).
                                                                                                 Hematol Oncol Clin North Am
                                                                                                  1997;11:71.
                                                                                                 Arch Pathol Lab Med 1999;123:114.
                                                                                                 Arch Pathol Lab Med 1999;123:126.
Immunoglobulins,    IgG makes up about 85% of total       ↑ IgG: Polyclonal: Autoimmune dis-           Quantitative immunoglobulin levels
  serum              serum immunoglobulins and pre-        eases (eg, SLE, rheumatoid arthritis),       are indicated in the evaluation of
(Ig)                 dominates late in immune responses. sarcoidosis, chronic liver diseases,           immunodeficiency or the quantitation
                     It is the only immunoglobulin to      some parasitic diseases, chronic or          of a paraprotein.
IgA: 78–367 mg/dL    cross the placenta.                   recurrent infections.                       IgG deficiency is associated with
IgG: 583–1761 mg/dL IgM antibody predominates early in    Monoclonal: Multiple myeloma (IgG             recurrent and occasionally severe
IgM: 52–335 mg/dL    immune responses.                     type), lymphomas, or other                   pyogenic infections.
[IgA: 0.78–3.67 g/L Secretory IgA plays an important role malignancies.                                The most common form of multiple
                                                          ↑ IgM: Polyclonal: Isolated infections




                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
IgG: 5.83–17.6 g/L   in host defense mechanisms by                                                      myeloma is the IgG type.
IgM: 0.52–3.35 g/L]  blocking transport of microbes        such as viral hepatitis, infectious mono-   Science 1986;231:1241.




                                                                                                                                              Immunoglobulins
                     across mucosal surfaces.              nucleosis, early response to bacterial or   Hematol Oncol Clin North Am
Marbled                                                    parasitic infection.                         1997;11:71.
$$$                                                       Monoclonal: Waldenström’s macro-             Am Fam Physician 1999;5:1885.
                                                           globulinemia, lymphoma.
                                                          ↑ IgA: Polyclonal: Chronic liver dis-
                                                           ease, chronic infections (especially of
                                                           the GI and respiratory tracts).
                                                          Monoclonal: Multiple myeloma (IgA).
                                                          ↓ IgG: Immunosuppressive therapy,
                                                           genetic (SCID, Wiskott-Aldrich syn-
                                                           drome, common variable immuno-
                                                           deficiency).
                                                          ↓ IgM: Immunosuppressive therapy.
                                                          ↓ IgA: Inherited IgA deficiency (ataxia-
                                                           telangiectasia, combined immuno-
                                                           deficiency disorders).




                                                                                                                                                                113
                                                                                                                                                                            114
Test /Range/Collection             Physiologic Basis                          Interpretation                               Comments
Inhibitor screen,        Test is useful for evaluating a pro-    Positive in: Presence of inhibitor: Anti-   LAC prolongs a PTT immediately and




                                                                                                                                                                            Pocket Guide to Diagnostic Tests
 plasma                   longed partial thromboplastin time      phospholipid antibodies (lupus anti-        is the most common inhibitor.
                          (PTT), prothrombin time (PT), or        coagulant (LAC) or anticardiolipin         Poor sensitivity for lupus anticoagulant




                                                                                                                                                         Inhibitor screen
Negative                  thrombin time. (Presence of heparin     antibodies), factor-specific antibodies.     owing to relatively high phospholipid
                          should first be excluded.)              Negative in: Factor deficiencies.             levels in this assay system.
Blue                     Patient’s plasma is mixed with normal                                               1– 4 hour incubation period may be
$$                        plasma and a PTT is performed. If                                                   needed to detect factor-specific anti-
Fill tube completely.     the patient has a factor deficiency,                                                 bodies with low in vitro affinities.
                          the postmixing PTT will be normal.                                                 About 15% of hemophilia A patients
                          If an inhibitor is present, it will be                                              develop inhibitor against factor VIII.
                          prolonged.                                                                         Semin Thromb Hemost 1994;20:79.
                                                                                                             Thromb Haemost 1996;16:146.
Insulin antibody,        Insulin antibodies develop in nearly  Increased in: Insulin therapy, type I         Insulin antibodies interfere with most
 serum                    all diabetics treated with insulin.   diabetics before treatment (secondary         assays for insulin.
                          Most antibodies are IgG and do not    to autoimmune pancreatic B cell              Insulin antibody test is not sensitive or




                                                                                                                                                         Insulin antibody
Negative                  cause clinical problems.              destruction).                                 specific for the detection of surrepti-
                         Occasionally, high-affinity antibodies                                                tious insulin use; use C-peptide level
Marbled                   can bind to exogenous insulin and                                                   (see p 62).
$$$                       cause insulin resistance.                                                          Anti-insulin and islet cell antibodies
                                                                                                              are poor predictors of IDDM and only
                                                                                                              roughly correlate with insulin require-
                                                                                                              ments in patients with diabetes.
                                                                                                             Diabetes 1996;45:1720.
                                                                                                             Diabetes Care 1996;19:146.
Insulin, immunoreac- Measures levels of insulin, either         Increased in: Insulin-resistant states     Measurement of serum insulin level




                                                                                                                                                      Insulin, immunoreactive
 tive, serum          endogenous or exogenous.                   (eg, obesity, type II diabetes mellitus,   has little clinical value except in the
                                                                 uremia, glucocorticoids, acromegaly),      diagnosis of fasting hypoglycemia.
6–35 µU/mL                                                       liver disease, surreptitious use of       An insulin-to-glucose ratio of >0.3 is
[42–243 pmol/L]                                                  insulin or oral hypoglycemic agents,       presumptive evidence of insulinoma.
                                                                 insulinoma (pancreatic islet cell tumor). C-peptide should be used as well as
Marbled                                                         Decreased in: Type I diabetes mellitus,     serum insulin to distinguish insulinoma
$$                                                               hypopituitarism.                           from surreptitious insulin use, since




                                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
Fasting sample                                                                                              C-peptide will be absent with exoge-
 required. Measure                                                                                          nous insulin use (see C-peptide, p 62).
 glucose concurrently.                                                                                     Eur J Endocrinol 1998;138:86.
Iron, serum              Plasma iron concentration is deter-     Increased in: Hemosiderosis (eg, multi- Absence of stainable iron on bone mar-
(Fe2+)                    mined by absorption from the intes-     ple transfusions, excess iron adminis-    row aspirate differentiates iron defi-
                          tine; storage in the intestine, liver,  tration), hemolytic anemia, pernicious    ciency from other causes of
50–175 µg/dL              spleen, bone marrow; rate of break-     anemia, aplastic or hypoplastic anemia, microcytic anemia (eg, thalassemia,
[9–31 µmol/L]             down or loss of hemoglobin; and rate viral hepatitis, lead poisoning, tha-        sideroblastic anemia, some chronic
                          of synthesis of new hemoglobin.         lassemia, hemochromatosis. Drugs:         disease anemias), but the procedure is
Marbled                                                           estrogens, ethanol, oral contraceptives. invasive and expensive. Serum iron,
$                                                                Decreased in: Iron deficiency, nephrotic iron-binding capacity, and transferrin
Avoid hemolysis.                                                  syndrome, chronic renal failure, many     saturation—or serum ferritin—may




                                                                                                                                                      Iron
                                                                  infections, active hematopoiesis, remis- obviate the need for bone marrow
                                                                  sion of pernicious anemia, hypo-          examination.
                                                                  thyroidism, malignancy (carcinoma),      Serum iron, iron-binding capacity, and
                                                                  postoperative state, kwashiorkor.         transferrin saturation are useful (see
                                                                                                            p 90) in screening family members
                                                                                                            for hereditary hemochromatosis.
                                                                                                           Recent transfusion will confound the
                                                                                                            test results.
                                                                                                           JAMA 1997;277:973.
                                                                                                           Ann Intern Med 1998;129:905.




                                                                                                                                                                                115
                                                                                                           Ann Intern Med 1998;129:923.
                                                                                                                                                                                  116
Test /Range/Collection             Physiologic Basis                          Interpretation                                Comments
Iron-binding capac-      Iron is transported in plasma com-      Increased in: Iron deficiency anemia,         Increased % transferrin saturation with




                                                                                                                                                                                  Pocket Guide to Diagnostic Tests
 ity, total, serum         plexed to transferrin, which is syn-   late pregnancy, infancy, hepatitis.          iron is seen in iron overload (iron poi-
(TIBC)                     thesized in the liver.                 Drugs: oral contraceptives.                  soning, hemolytic anemia, sideroblas-
                         Total iron-binding capacity is calcu-   Decreased in: Hypoproteinemic states          tic anemia, thalassemia,
250–460 µg/dL




                                                                                                                                                          Iron-binding capacity
                           lated from transferrin levels mea-     (eg, nephrotic syndrome, starvation,         hemochromatosis, pyridoxine defi-
[45–82 µmol/L]             sured immunologically. Each            malnutrition, cancer), hyperthyroidism,      ciency, aplastic anemia).
                           molecule of transferrin has two iron- chronic inflammatory disorders, chro-         Decreased % transferrin saturation
Marbled                    binding sites, so its iron-binding     nic liver disease, other chronic disease.    with iron is seen in iron deficiency
$$                         capacity is 1.47 mg/g.                                                              (usually saturation <16%).
                         Normally, transferrin carries an                                                     Transferrin levels can also be used to
                           amount of iron representing about                                                   assess nutritional status.
                           16–60% of its capacity to bind iron                                                Recent transfusion will confound the
                           (ie, % saturation of iron-binding                                                   test results.
                           capacity is 16–60%).                                                               Clin Chem 1997;43:2408.
                                                                                                              Ann Intern Med 1998;129:925.
                                                                                                              Ann Intern Med 1998;129:962.
Lactate dehydroge-     LDH is an enzyme that catalyzes the Increased in: Tissue necrosis, especially          LDH is elevated after myocardial
 nase, serum             interconversion of lactate and pyru-   in acute injury of cardiac muscle,              infarction (for 2–7 days), in liver con-
(LDH)                    vate in the presence of NAD/NADH. RBCs, kidney, skeletal muscle, liver,                gestion (eg, in CHF), and in P carinii
                       It is widely distributed in body cells   lung, or skin. Commonly elevated in             pneumonia.
88–230 U/L               and fluids.                             various carcinomas and in Pneumo-             LDH is not a useful liver function test,




                                                                                                                                                           Lactate dehydrogenase
[1.46–3.82 µkat/L]     Because LDH is highly concentrated       cystis carinii pneumonia (78–94%) and           and it is not specific enough for the
  (laboratory-specific)   in red blood cells (RBCs), spuriously lymphoma in AIDS. Marked elevations              diagnosis of hemolytic or megalo-
                         elevated serum levels will occur if    occur in hemolytic anemias, vitamin             blastic anemias.




                                                                                                                                                                                              Common Laboratory Tests: Selection and Interpretation
Marbled                  RBCs are hemolyzed during              B12 deficiency anemia, folate deficiency        Its main diagnostic use has been in
$                        specimen collection.                   anemia, polycythemia vera, thrombotic           myocardial infarction, when the crea-
Hemolyzed specimens                                             thrombocytopenic purpura (TTP),                 tine kinase-MB elevation has passed
  are unacceptable.                                             hepatitis, cirrhosis, obstructive jaundice,     (see CK-MB, p 79, and Figure 8–17,
                                                                renal disease, musculoskeletal disease,         p 353). LDH isoenzymes are preferred
                                                                CHF. Drugs causing hepatotoxicity               over total serum LDH in late diagno-
                                                                (eg, acetaminophen) or hemolysis.               sis of MI, but both tests are now being
                                                               Decreased in: Drugs: clofibrate, fluoride          replaced by cardiac troponin I levels.
                                                                (low dose).                                   Arch Intern Med 1997;157:1441.
                                                                                                              Chest 1997;111:1187.
Lactate dehydroge-       LDH consists of five isoenzymes          Increased in: LDH1/LDH2 >0.85 in             The only clinical indication for LDH




                                                                                                                                                           Lactate dehydrogenase isoenzymes
 nase isoenzymes,         separable by electrophoresis.           myocardial infarction, hemolysis             isoenzyme measurement has been to
 serum                   The fraction with the greatest elec-     (hemolytic or megaloblastic anemia)          rule out myocardial infarction in pa-
(LDH isoenzymes)          trophoretic mobility is called LDH1;    or acute renal infarction. LDH5 is           tients presenting more than 24 hours
                          the one with the least, LDH5.           increased in liver disease, congestive       after onset of symptoms (LDH1/LDH2
LDH1/LDH2: < 0.85        LDH1 is found in high concentrations     heart failure, skeletal muscle injury,       >0.85 is usually present within
                          in heart muscle, RBCs, and kidney       and essential thrombocythemia.               12–48 hours). It may also be helpful
Marbled                   cortex; LDH5 in skeletal muscle                                                      if CK-MB results cannot be easily
$$                        and liver.                                                                           interpreted. The test is being replaced
Hemolyzed specimens                                                                                            by measurement of cardiac troponin I
 are unacceptable.                                                                                             (see CK-MB, p 79).
                                                                                                              Arch Intern Med 1997;157:1441.




                                                                                                                                                                                              117
                                                                                                                                                               118
Test /Range/Collection           Physiologic Basis                         Interpretation                               Comments
Lactate, venous blood Severe tissue anoxia leads to anaero-   Increased in: Lactic acidosis, ethanol      Lactic acidosis should be suspected




                                                                                                                                                               Pocket Guide to Diagnostic Tests
                       bic glucose metabolism with pro-        ingestion, sepsis, shock, liver disease,    when there is a markedly increased
0.5–2.0 meq/L          duction of lactic acid.                 diabetic ketoacidosis, muscular exer-       anion gap (>18 meq/L) in the absence
 [mmol/L]                                                      cise, hypoxia; regional hypoperfusion       of other causes (eg, renal failure,
                                                               (bowel ischemia); prolonged use of a        ketosis, ethanol, methanol, or
Gray                                                           tourniquet (spurious elevation); type I     salicylate).
$$                                                             glycogen storage disease, fructose         Lactic acidosis is characterized by lac-
Collect on ice in gray-                                        1,6-diphosphatase deficiency (rare),         tate levels >5 mmol/L in association




                                                                                                                                                     Lactate
 top tube containing                                           pyruvate dehydrogenase deficiency.           with metabolic acidosis. Tissue hypo-
 fluoride to inhibit in                                         Drugs: phenformin, metformin, isoni-        perfusion is the most common cause.
 vitro glycolysis and                                          azid toxicity.                              Blood lactate levels may indicate
 lactic acid production.                                                                                   whether perfusion is being restored
                                                                                                           by therapy.
                                                                                                          Am J Med 1996;101:109.
                                                                                                          Ann Intern Med 1997;127:170.
                                                                                                          Medicine 1998;77:73.
                                                                                                          Semin Nephrol 1998;18:83.
Lead, whole blood (Pb) Lead salts are absorbed through inges- Increased in: Lead poisoning, including      Subtle neurologic impairment may be
                         tion, inhalation, or the skin. About  abnormal ingestion (especially lead-         detectable in children with lead levels
Child (<6 yrs):          5–10% of ingested lead is found in    containing paint, moonshine whiskey),        of 15 µg/dL and in adults at 30 µg/dL;
 <10 mg/dL               blood and 95% of this is in erythro-  occupational exposures (metal smelters,      full-blown symptoms appear at
Child (>6 yrs):          cytes. 80–90% is taken up by bone,    miners, welders, storage battery work-       >60 µg/dL.
 <25 mg/dL               where it is relatively inactive.      ers, auto manufacturers, ship builders,     Most chronic lead poisoning leads to a
Adult: <40 µg/dL        Lead poisons enzymes by binding to     paint manufacturers, printing workers,       moderate anemia with basophilic
[Child (<6):             protein disulfide groups, leading to   pottery workers, gasoline refinery            stippling of erythrocytes on peri-




                                                                                                                                                      Lead
 <0.48 mmol/L




                                                                                                                                                                                     Common Laboratory Tests: Selection and Interpretation
                         cell death.                           workers), retained bullets.                  pheral blood smear.
Child (>6): <1.21 mol/L Lead levels fluctuate. Several speci-                                               Acute poisoning is rare and associated
Adult: <1.93 µmol/L]     mens may be needed to rule out                                                     with abdominal pain and constipa-
                         lead poisoning.                                                                    tion. Blood lead levels are useful in
Navy                                                                                                        the diagnosis.
$$                                                                                                         Industrial workers’ limit: <50 µg/dL.
Use trace metal-free                                                                                       Pediatrics 1994;93:201.
 navy blue top tube                                                                                        Pediatrics 1996;97:79.
 with heparin.                                                                                             Ann Intern Med 1999;130:7.
Lecithin/sphin-         This test is used to estimate lung matu- Increased in: Contamination of amni-    Test identifies fetal lung maturity
 gomyelin ratio,         rity in fetuses at risk for hyaline      otic fluid by blood, meconium, or vagi- effectively only 60% of the time: ie,




                                                                                                                                                      Lecithin/sphingomyelin ratio
 amniotic fluid           membrane disease.                        nal secretions that contain lecithin    40% of fetuses with an L/S ratio of
(L/S ratio)             As fetal pulmonary surfactant matures, (false-positives).                         <2.0 will not develop hyaline mem-
                         there is a rapid rise in amniotic fluid Decreased in: Fetal lung immaturity;      brane disease.
>2.0 (method-            lecithin content. To circumvent the      95% of normal fetuses.                 Precision of L/S ratio test is poor:
 dependent)              dependency of lecithin concentra-                                                results on a single sample may vary
                         tions on amniotic fluid volume and                                                by ± 25%.
$$$                      analytic recovery of lecithin, the                                              Test is not reliable to assess fetal lung
Collect in a plastic     assay examines the lecithin/                                                     maturity in offspring of diabetic
 tube.                   sphingomyelin ratio.                                                             mothers.
                                                                                                         Med Decis Making 1990;10:201.
                                                                                                         Clin Chem 1994;40:541.




                                                                                                                                                                                     119
                                                                                                         Am J Obstet Gynecol 1998;179;1640.
                                                                                                                                                                                        120
Test /Range/Collection            Physiologic Basis                          Interpretation                              Comments
Legionella antibody,    Legionella pneumophila is a weakly      Increased in: Legionella infection          A greater than fourfold rise in titer to
                                                                                                             >1 128 in specimens gathered more




                                                                                                                                                                                        Pocket Guide to Diagnostic Tests
 serum                   staining gram-negative bacillus that    (80% of patients with pneumonia have
                         causes Pontiac fever (acute             a fourfold rise in titer); cross-reactions  than 3 weeks apart indicates recent
<1 32 titer              influenza-like illness) and Legion-      with other infectious agents (Yersinia      infection. A single titer of >1 256 is




                                                                                                                                                       Legionella antibody
                         naire’s disease (a pneumonia that       pestis [plague], Francisella tularensis     considered diagnostic.
Marbled                  may progress to a severe multi-         [tularemia], Bacteroides fragilis,         About 50–60% of cases of legionellosis
$$$                      system illness). It does not grow on    Mycoplasma pneumoniae, Leptospira           may have a positive direct fluorescent
Submit paired sera, one routine bacteriologic culture media.     interrogans, campylobacter serotypes). antibody test. Culture can have a sen-
 collected within       Antibodies are detected by indirect                                                  sitivity of 50%. All three methods
 2 weeks of illness and immunofluorescent tests to                                                            may increase sensitivity to 90%.
 another 2–3 weeks       serogroup 1 of L pneumophila.                                                      This test is species-specific. Polyvalent
 later.                 There are at least six serogroups of                                                 antiserum is needed to test for all
                         L pneumophila and at least                                                          serogroups and species.
                         22 species of Legionella.                                                          Epidemiol Infect 1994;112:347.
                                                                                                            Clin Infect Dis 1996;23:656.
Leukocyte alkaline       The test measures the amount of alka- Increased in: Leukemoid reaction (eg, Test may be helpful for distinguishing
 phosphatase,             line phosphatase in neutrophils in a   severe infections), polycythemia vera,  leukemoid reactions (high-normal or




                                                                                                                                                       Leukocyte alkaline phosphatase
 whole blood              semiquantitative fashion.              myelofibrosis with myeloid metaplasia. increased LAP) from chronic myeloid
(LAP)                    Neutrophilic leukocytes on a periph- Decreased in: Chronic myeloid leuke-       leukemia (decreased LAP), but it is
                          eral blood smear are stained for alka- mia, paroxysmal nocturnal hemo-         poorly reproducible.
40–130                    line phosphatase activity and then     globinuria.                            Br J Haematol 1997;96:815.
Based on 0–4+ rating      100 are scored on a scale from 0 to
 of 100 PMNs              4+ on the basis of the intensity of
                          the dye in their cytoplasm.
Green
$$
Blood smear from fin-
 ger stick preferred.
 If collecting venous
 blood, make smear
 as soon as possible.
Leukocyte (white        Measure of the total number of leuko- Increased in: Infection, inflammation,       A spurious increase may be seen when
 blood cell) count,      cytes in whole blood.                 hematologic malignancy, leukemia,           there are a large number of nucleated




                                                                                                                                                     Leukocyte count, total
 total, whole blood     Counted on automated instruments       lymphoma. Drugs: corticosteroids.           red cells.
(WBC count)              using light scattering or electrical Decreased in: Aplastic anemia               WBC count is a poor predictor of
                         impedance after lysis of red blood    (decreased production), B12 or folate       severity of disease in the diagnosis of
3.4–10 × 103/µL          cells. WBCs are distinguished from    deficiency (maturation defect), sepsis       appendicitis.
 [× 106/L]               platelets by size.                    (decreased survival). Drugs: phenoth-      Lab Med 1983;14:509.
Panic: <1.5 × 103/µL                                           iazines, chloramphenicol, aminopyrine.     J Clin Pathol 1996;49:664.




                                                                                                                                                                              Common Laboratory Tests: Selection and Interpretation
                                                                                                          Am Surg 1998;64:983.
Lavender
$
Lipase, serum           Lipases are responsible for hydrolysis Increased in: Acute, recurrent, or chro- The sensitivity of lipase in acute pan-
                         of glycerol esters of long-chain fatty nic pancreatitis, pancreatic pseudocyst, creatitis is similar to that of amylase;
0–160 U/L                acids to produce fatty acids and       pancreatic malignancy, peritonitis, bil-  lipase remains elevated longer than
[0–2.66 µkat/L]          glycerol.                              iary disease, hepatic disease, diabetes   amylase. The specificity of lipase and
 (laboratory-specific)   Lipases are produced in the liver,      mellitus (especially diabetic keto-       amylase in acute pancreatitis is simi-
                         intestine, tongue, stomach, and many acidosis), intestinal disease, gastric      lar, though both are poor.
Marbled                  other cells.                           malignancy or perforation.               Test sensitivity is not very good for




                                                                                                                                                     Lipase
$$                      Assays are highly dependent on the                                                chronic pancreatitis or pancreatic
                         substrate used.                                                                  cancer.
                                                                                                         Lipase to amylase ratio is not useful in
                                                                                                          distinguishing alcoholic from non-
                                                                                                          alcoholic pancreatitis.
                                                                                                         Arch Pathol Lab Med 1991;115:325.
                                                                                                         Clin Chem 1991;37:447.
                                                                                                         Am J Gastroenterol 1995;90:67.




                                                                                                                                                                              121
                                                                                                                                                                            122
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Luteinizing hormone, LH is stimulated by the hypothalamic Increased in: Primary hypogonadism,             Intact human chorionic gonadotropin




                                                                                                                                                                            Pocket Guide to Diagnostic Tests
  serum               hormone gonadotropin-releasing          polycystic ovary syndrome, post-             (hCG) cross-reacts with LH in most
(LH)                  hormone (GnRH). It is secreted from menopause.                                       immunoassays so that LH levels
                      the anterior pituitary and acts on the Decreased in: Pituitary or hypothalamic       appear to be falsely elevated in preg-




                                                                                                                                                    Luteinizing hormone
Male: 1–10 mIU/mL     gonads.                                 failure, anorexia nervosa, severe stress,    nancy or in individuals with hCG-
Female: (mIU/mL)     LH is the principal regulator of steroid malnutrition, Kallman’s syndrome             secreting tumors.
   Follicular 1–18    biosynthesis in the ovary and testis.   (gonadotropin deficiency associated          Repeated measurement may be required
   Luteal 0.4–20                                              with anosmia). Drugs: digoxin, oral          to diagnose gonadotropin deficiencies.
   Midcycle peak                                              contraceptives, phenothiazines.             Measurement of total testosterone is
     24–105                                                                                                the test of choice to diagnose poly-
   Postmenopausal                                                                                          cystic ovary syndrome.
     15–62                                                                                                Br J Obstet Gynaecol 1992;99:232.
(laboratory-specific)                                                                                      J Clin Endocrinol Metab
                                                                                                           1994;78:1208.
Marbled                                                                                                   Obstet Gynecol 1994;84:613.
$$
Lyme disease anti-       Test detects the presence of antibody Positive in: Lyme disease, asympto-        Test is less sensitive in patients with
 body, serum              to Borrelia burgdorferi, the etiologic matic individuals living in endemic       only a rash. Since culture or direct
                          agent in Lyme disease, an inflamma- areas, syphilis (Treponema pallidum),         visualization of the organism is diffi-




                                                                                                                                                    Lyme disease antibody
ELISA: negative           tory disorder transmitted by the ticks tick-borne relapsing fever (Borrelia      cult, serologic diagnosis (by ELISA)
 (<1 8 titer)             Ixodes dammini, I pacificus, and        hermsii).                                 is indicated, though sensitivity and
Western blot:             I scapularis in the northeastern and Negative during the first 5 weeks of         specificity and standardization of
 non-reactive             midwestern, western, and southeast-    infection or after antibiotic therapy.    procedure between laboratories need
                          ern USA, respectively.                                                           improvement.
Marbled                  Detects IgM antibody, which develops                                             Cross-reactions may occur with
$                         within 3–6 weeks after the onset of                                              syphilis (should be excluded by RPR
                          rash; or IgG, which develops within                                              and treponemal antibody assays).
                          6–8 weeks after the onset of disease.                                           N Engl J Med 1989;321:586.
                          IgG antibody may persist for months.                                            Ann Intern Med 1991;114:472.
                                                                                                          Ann Intern Med 1997;127:1106.
Magnesium, serum      Magnesium is primarily an intracellu- Increased in: Dehydration, tissue trauma,     Hypomagnesemia is associated with
(Mg2+)                 lar cation (second most abundant,      renal failure, hypoadrenocorticism,          tetany, weakness, disorientation,
                       60% found in bone); it is a necessary hypothyroidism. Drugs: aspirin                and somnolence.
1.8–3.0 mg/dL          cofactor in numerous enzyme sys-       (prolonged use), lithium, magnesium         A magnesium deficit may exist with
[0.75–1.25 mmol/L]     tems, particularly ATPases.            salts, progesterone, triamterene.            little or no apparent change in serum
Panic: <0.5 or >4.5   In extracellular fluid, it influences    Decreased in: Chronic diarrhea, enteric       level.




                                                                                                                                                   Magnesium
 mg/dL                 neuromuscular response and             fistula, starvation, chronic alcoholism,     There is a progressive reduction in
                       irritability.                          total parenteral nutrition with inade-       serum magnesium level during normal




                                                                                                                                                                                 Common Laboratory Tests: Selection and Interpretation
Marbled               Magnesium concentration is deter-       quate replacement, hypoparathyroidism        pregnancy (related to hemodilution).
$                      mined by intestinal absorption, renal (especially post parathyroid surgery),       Crit Care Med 1998;26:1949.
                       excretion, and exchange with bone      acute pancreatitis, chronic glomeru-        Crit Care Med 1998;26:2048.
                       and intracellular fluid.                lonephritis, hyperaldosteronism, dia-       Semin Nephrol 1998;18:58.
                                                              betic ketoacidosis. Drugs: albuterol,
                                                              amphotericin B, calcium salts, cispla-
                                                              tin, citrates (blood transfusion), cyclo-
                                                              sporine, diuretics, ethacrynic acid.
                      MCH indicates the amount of hemo-                                                   MCH is calculated from measured val-




                                                                                                                                                   Mean corpuscular hemoglobin
Mean corpuscular                                               Increased in: Macrocytosis.
 hemoglobin, blood     globin per red blood cell in absolute   Decreased in: Microcytosis (iron defi-       ues of hemoglobin (Hb) and red cell
(MCH)                  units.                                   ciency, thalassemia). Hypochromia          count (RBC) by the formula:
                      Low MCH can mean hypochromia or           (lead poisoning, sideroblastic anemia,
26–34 pg               microcytosis or both.                    anemia of chronic disease).                                    Hb
                                                                                                                      MCH =
                      High MCH is evidence of                                                                                 RBC
Lavender               macrocytosis.
$                                                                                                         Obstet Gynecol 1999;93:427.




                                                                                                                                                                                 123
                                                                                                                                                                                                 124
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Mean corpuscular         MCHC describes how fully the            Increased in: Marked spherocytosis.       Lab Med 1983;14:509.




                                                                                                                                                     Mean corpuscular hemoglobin concentration

                                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
 hemoglobin con-          erythrocyte volume is filled with        Spuriously increased in autoagglutina-
 centration, blood        hemoglobin and is calculated from       tion, hemolysis (with spuriously high
(MCHC)                    measurement of hemoglobin (Hb),         Hb or low MCV or RBC), lipemia.
                          mean corpuscular volume (MCV),          Cellular dehydration syndromes,
31–36 g/dL                and red cell count (RBC) by the         xerocytosis.
[310–360 g/L]             formula:                               Decreased in: Hypochromic anemia
                                                                  (iron deficiency, thalassemia, lead poi-
Lavender                                                          soning), sideroblastic anemia, anemia of
$                                             Hb                  chronic disease. Spuriously decreased
                                MCHC =
                                           MCV × RBC              with high white blood cell count, low
                                                                  Hb, or high MCV or RBC.




Mean corpuscular         Average volume of the red cell is       Increased in: Liver disease, megalo-     MCV can be normal in combined iron
 volume, blood            measured by automated instrument,       blastic anemia (folate, B12 deficien-     and folate deficiency.




                                                                                                                                                     Mean corpuscular volume
(MCV)                     by electrical impedance, or by light    cies), reticulocytosis, newborns.       In patients with two red cell popula-
                          scatter.                                Spurious increase in autoagglutination, tions (macrocytic and microcytic),
80–100 fL                                                         high white blood cell count. Drugs:      MCV may be normal.
                                                                  methotrexate, phenytoin, zidovudine.    MCV is an insensitive test in the evalu-
Lavender                                                         Decreased in: Iron deficiency,             ation of anemia. Patients with iron
$                                                                 thalassemia; decreased or normal in      deficiency anemia or pernicious ane-
                                                                  anemia of chronic disease.               mia commonly have a normal MCV.
                                                                                                          J Gen Intern Med 1990;5:187.
                                                                                                          Br J Haematol 1994;88:443.
                                                                                                          Am J Clin Pathol 1996;106:201.
Metanephrines, urine      Catecholamines, secreted in excess by Increased in: Pheochromocytoma          First-line test for diagnosis of pheo-
                           pheochromocytomas, are metabo-        (96% sensitivity, 98% specificity),      chromocytoma (see Pheochromo-
0.3–0.9 mg/24 h            lized by the enzyme catechol-O-       neuroblastoma, ganglioneuroma.          cytoma algorithm, p 355).
[1.6–4.9 µmol/24 h]        methyltransferase to metanephrines,   Drugs: monoamine oxidase inhibitors.   Since <0.1% of hypertensives have a
                           and these are excreted in the urine.                                          pheochromocytoma, routine screen-
Urine bottle containing                                                                                  ing of all hypertensives would yield a




                                                                                                                                                  Metanephrines
 hydrochloric acid                                                                                       positive predictive value of <10%.
$$$                                                                                                     Avoid overutilization of tests. Do not




                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
Collect 24-hour urine.                                                                                   order urine vanillylmandelic acid,
                                                                                                         urine catecholamines, and plasma cat-
                                                                                                         echolamines at the same time.
                                                                                                        Plasma catecholamine levels are often
                                                                                                         spuriously increased when drawn in
                                                                                                         the hospital setting.
                                                                                                        Mayo Clin Proc 1990;65:88.
                                                                                                        Ann Intern Med 1995;123:101.
                                                                                                        Ann Intern Med 1996;125:331.
Methanol, whole           Serum methanol levels >20 mg/dL are Increased in: Methanol intoxication.      Methanol intoxication is associated
 blood                     toxic and levels >40 mg/dL are                                                with metabolic acidosis and an
                           life-threatening.                                                             osmolal gap.
Negative                                                                                                Methanol is commonly ingested in its




                                                                                                                                                  Methanol
                                                                                                         pure form or in cleaning and copier
Green or lavender                                                                                        solutions.
$$                                                                                                      Acute ingestion causes an optic neuri-
                                                                                                         tis that may result in blindness.
                                                                                                        Med Toxicol 1986;1:309.
                                                                                                        Ann Emerg Med 1995;26:202.




                                                                                                                                                                  125
                                                                                                                                                                        126
Test /Range/Collection            Physiologic Basis                         Interpretation                            Comments
Methemoglobin,           Methemoglobin has its heme iron in    Increased in: Hemoglobin variants         Levels of 1.5 g/dL (10% of total Hb)




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
 whole blood              the oxidized ferric state and thus    (HbM) (rare), methemoglobin reduc-        result in visible cyanosis.
(MetHb)                   cannot combine with and transport     tase deficiency. Oxidant drugs such as    Patients with levels of about 35%
                          oxygen.                               sulfonamides (dapsone, sulfasalazine),    have headache, weakness, and




                                                                                                                                                   Methemoglobin
<0.005 g/dL              Methemoglobin can be assayed spec-     nitrites and nitrates, aniline dyes,      breathlessness.
[<0.5 g/L]                trophotometrically by measuring the   phenacetin, anesthetics such as          Levels in excess of 70% are usually
                          decrease in absorbance at 630–635 nm benzocaine.                                fatal.
Lavender                  due to the conversion of methemoglo-                                           Fetal methemoglobin is accurately
$$                        bin to cyanmethemoglobin with                                                   measured using newer multiple-
Analyze promptly.         cyanide.                                                                        wavelength spectrophotometers.
                                                                                                         Am J Med Sci 1985;289:200.
                                                                                                         Am J Hematol 1993;42:7.
                                                                                                         Clin Chem 1998;44:1569.
Methylmalonic acid,      Elevation of serum methylmalonic     Increased in: Vitamin B12 (cobalamin)      Explanation of high frequency (5–15%)
 serum                    acid in cobalamin deficiency results  deficiency (95%), pernicious anemia,        of increased serum methylmalonic
                          from impaired conversion of methyl- renal insufficiency, elderly (5–15%).        acid in the elderly with low or normal
0–0.4 µmol/L              malonyl-CoA to succinyl-CoA, a                                                  serum cobalamin is unclear. Only a
                          pathway involving methylmalonyl-                                                small number have pernicious anemia




                                                                                                                                                   Methylmalonic acid
Marbled                   CoA mutase as enzyme and adeno-                                                 confirmed.
$$                        sylcobalamin as coenzyme.                                                      Normal levels can exclude vitamin B12
                                                                                                          deficiency in the presence of low un-
                                                                                                          explained cobalamin levels found in
                                                                                                          lymphoid disorders.
                                                                                                         Test is usually normal in HIV patients
                                                                                                          who may have low vitamin B12 levels
                                                                                                          without cobalamin deficiency, because
                                                                                                          of low vitamin B12 binding protein.
                                                                                                         Semin Hematol 1999;36:29.
                                                                                                         Semin Hematol 1999;36:35.
                                                                                                         Am J Clin Nutr 1997;66:741.
Metyrapone test        The metyrapone stimulation test        Decreased in: An 8 AM 11-deoxycortisol   The metyrapone test can be useful in
 (overnight), plasma    assesses both pituitary and adrenal    level ≤7 µg/dL indicates primary or      steroid-treated patients to assess the
 or serum               reserve and is mainly used to diag-    secondary adrenal insufficiency.          extent of suppression of the pituitary-
                        nose secondary adrenal insufficiency                                             adrenal axis.
8 AM cortisol:          (see Adrenocortical Insufficiency                                               The use of an extended metyrapone




                                                                                                                                                  Metyrapone test (overnight)
<10 µg/dL               algorithm, p 338).                                                              test in the differential diagnosis of
[<280 nmol/L]          Metyrapone is a drug that inhibits                                               ACTH-dependent Cushing’s syn-
8 AM 11-deoxycortisol: adrenal 11 β-hydroxylase and blocks                                              drome (pituitary versus ectopic)
 >7 µg/dL




                                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
                        cortisol synthesis. The consequent                                              has been questioned.
[>202 nmol/L]           fall in cortisol increases release of                                          Ann Intern Med 1994;121:318.
                        ACTH and hence production of                                                   Clin Endocrinol 1996;45:483.
Marbled, lavender,      steroids formed proximal to the                                                Clin Endocrinol 1997;47:145.
 or green               block (eg, 11-deoxycortisol).
$$$
Give 2.0–2.5 g of
 metyrapone orally at
 12:00 midnight. Draw
 serum cortisol and
 11–deoxycortisol
 levels at 8:00 AM.




                                                                                                                                                                                127
                                                                                                                                                                    128
Test /Range/Collection            Physiologic Basis                         Interpretation                            Comments
 2-Microglobulin,        β2-Microglobulin is a portion of the    Increased in: Any type of inflammation, Of tests used to predict progression to




                                                                                                                                                                    Pocket Guide to Diagnostic Tests
 serum                     HLA molecule on cell surfaces syn-     autoimmune disorders, lymphoid         AIDS in HIV-infected patients, CD4
(β2-M)                     thesized by all nucleated cell types   malignancies, multiple myeloma, viral  cell number has the most predictive
                           and is present in all body fluids.      infections (HIV, CMV). Marked eleva- power, followed closely by
<0.2 mg/dL               It is increased in many conditions that tion in patients with amyloidosis and   β2-microglobulin.
[<2.0 mg/L]                are accompanied by high cell           renal failure.                        Asymptomatic HIV patients with ele-
                           turnover.                                                                     vated β2-microglobulin levels have a
Marbled                                                                                                  two- to threefold increased chance of




                                                                                                                                                  2-Microglobulin
$$$                                                                                                      disease progression.
                                                                                                        However, β2-microglobulin does not
                                                                                                         provide information significantly
                                                                                                         more useful than the combination of
                                                                                                         serial CD4 count and serum IgA in
                                                                                                         predicting onset of AIDS.
                                                                                                        β2-Microglobulin is of prognostic value
                                                                                                         in multiple myeloma: serum level in-
                                                                                                         creases with increasing tumor mass.
                                                                                                        AIDS 1994;8:911.
                                                                                                        Semin Hematol 1997;34(1 Suppl):29.
                                                                                                        J Am Soc Nephrol 1998;9:1723.
Micro-               The MHA-TP test measures specific         Increased in: Syphilis: primary              Test is used to confirm reactive serolo-




                                                                                                                                                       Microhemagglutination-Treponema pallidum Mitochondrial antibody
 hemagglutination-    antibody against T pallidum in a         (64–87%), secondary (96–100%), late          gic tests for syphilis (RPR or VDRL).
 Treponema pallidum, patient’s serum by agglutination of       latent (96–100%), tertiary (94–100%);       Compared to FTA-ABS, MHA-TP is
 serum                T pallidum antigen-coated erythro-       infectious mononucleosis, collagen-          slightly less sensitive in all stages of
(MHA-TP)              cytes. Antibodies to nonpathogenic       vascular diseases, hyperglobulinemia         syphilis and becomes reactive some-
                      treponemes are first removed by           and dysglobulinemia.                         what later in the disease.
Nonreactive           binding to nonpathogenic trepone-                                                    Because test usually remains positive
                      mal antigens.                                                                         for long periods of time regardless of




                                                                                                                                                                                                                         Common Laboratory Tests: Selection and Interpretation
Marbled                                                                                                     therapy, it is not useful in assessing
$$                                                                                                          the effectiveness of therapy.
                                                                                                           In one study, 36 months after treatment
                                                                                                            of syphilis, 13% of patients had non-
                                                                                                            reactive MHA-TP tests.
                                                                                                           Ann Intern Med 1986;104:368.
                                                                                                           J Infect Dis 1990;162:862.
                                                                                                           Ann Intern Med 1991;114:1005.
                                                                                                           Clin Microbiol Rev 1995;8:1.
Mitochondrial anti-   Qualitative measure of antibodies      Increased in: Primary biliary cirrhosis       Primarily used to distinguish primary
 body, serum           against hepatic mitochondria.          (87–98%), chronic active hepatitis            biliary cirrhosis (antibody present)
                      Rabbit hepatocytes are incubated first   (25–28%); lower titers in viral hepatitis,    from extrahepatic biliary obstruction
Negative               with serum and then (after washing)    infectious mononucleosis, neoplasms,          (antibody absent).
                       with a fluorescein-tagged antibody to cryptogenic cirrhosis (25–30%).                Hepatology 1986;6:381.
Marbled                human immunoglobulin. Hepatocytes                                                   Acta Med Scand 1986;220:241.
$$                     are then viewed for presence of cyto-                                               Dig Dis 1992;10:85.
                       plasmic staining.                                                                   Am J Gastroenterol 1999;94:47.




                                                                                                                                                                                                                         129
                                                                                                                                                                                         130
Test /Range/Collection             Physiologic Basis                        Interpretation                              Comments
Neutrophil cytoplas-     Measurement of autoantibodies in       Positive in: Wegener’s granulomatosis, Test sensitivity for Wegener’s granulo-




                                                                                                                                                                                         Pocket Guide to Diagnostic Tests
 mic antibodies,          serum against cytoplasmic con-         systemic vasculitis, crescentic glomeru- matosis ranges from 56% to 96%.
 serum                    stituents of neutrophils. (See also    lonephritis, paraneoplastic vasculitis,   depending on the population studied.
(ANCA)                    Autoantibodies table, p 367.)          ulcerative colitis.                      Test specificity for Wegener’s granulo-




                                                                                                                                                     Neutrophil cytoplasmic antibodies
                                                                                                           matosis is claimed to be high (99%)
Negative                                                                                                   when requiring diffuse cytoplasmic
                                                                                                           staining for a positive result, but
Marbled                                                                                                    interpretation is highly technique-
$$$                                                                                                        dependent.
                                                                                                          In the patient with systemic vasculitis,
                                                                                                           elevated ANCA levels imply active
                                                                                                           disease and high likelihood of recur-
                                                                                                           rence. However, ANCA levels can be
                                                                                                           persistently elevated and should be
                                                                                                           used in conjunction with other clini-
                                                                                                           cal indices in treatment decisions.
                                                                                                          N Engl J Med 1988;318:1651.
                                                                                                          Ann Intern Med 1989;111:28.
                                                                                                          Am J Kidney Dis 1995;25:380.
                                                                                                          Ann Intern Med 1995;123:925.
Nuclear antibody,       Heterogeneous antibodies to nuclear     Elevated in: Patients over age 65           A negative ANA test does not com-
 serum                   antigens (DNA and RNA, histone          (35–75%, usually in low titers), sys-       pletely rule out SLE, but alternative
(ANA)                    and nonhistone proteins). Nuclear       temic lupus erythematosus (98%),            diagnoses should be considered.
<1 20                    antibody is measured in serum by        drug-induced lupus (100%), Sjögren’s       Pattern of ANA staining may give
                         layering the patient’s serum over       syndrome (80%), rheumatoid arthritis        some clues to diagnoses, but since the




                                                                                                                                                        Nuclear antibody
Marbled                  human epithelial cells and detecting    (30–50%), scleroderma (60%), mixed          pattern also changes with serum dilu-
$$                       the antibody with fluorescein-           connective tissue disease (100%),           tion, it is not routinely reported. Only
                         conjugated polyvalent antihuman         Felty’s syndrome, mononucleosis,            the rim (peripheral) pattern is highly




                                                                                                                                                                            Common Laboratory Tests: Selection and Interpretation
                         immunoglobulin.                         hepatic or biliary cirrhosis, hepatitis,    specific (for SLE).
                                                                 leukemia, myasthenia gravis, dermato-      Not useful as a screening test. Should
                                                                 myositis, polymyositis, chronic renal       be used only when there is clinical
                                                                 failure.                                    evidence of a connective tissue
                                                                                                             disease.
                                                                                                            West J Med 1987;147:210.
                                                                                                            Arch Intern Med 1996;156:1421.
                                                                                                            Clin Chem 1997;43:1981.
Oligoclonal bands,      Electrophoretic examination of IgG      Positive in: Multiple sclerosis (88%),  Test is indicated only when multiple
 serum and CSF           found in CSF may show oligoclonal       CNS syphilis, subacute sclerosing pan- sclerosis is suspected clinically.




                                                                                                                                                        Oligoclonal bands
                         bands not found in serum. This sug-     encephalitis, other CNS inflammatory Test interpretation is very subjective.
Negative                 gests local production in CSF of        diseases.                              IgG index is a more reliable test ana-
                         limited species of IgG.                                                         lytically, but neither test is specific
Marbled and glass or                                                                                     for multiple sclerosis.
 plastic tube for CSF                                                                                   Neurology 1985;35:212.
$$                                                                                                      Mayo Clin Proc 1989;64:577.
Collect serum and CSF                                                                                   Am J Clin Pathol 1998;109:585.
 simultaneously.




                                                                                                                                                                            131
                                                                                                                                                                          132
Test /Range/Collection             Physiologic Basis                         Interpretation                              Comments
Osmolality, serum        Test measures the osmotic pressure of Increased in: Diabetic ketoacidosis,         If the difference between calculated




                                                                                                                                                                          Pocket Guide to Diagnostic Tests
(Osm)                     serum by the freezing point depres-    nonketotic hyperosmolar hyper-               and measured serum osmolality is
                          sion method.                           glycemic coma, hypernatremia sec-            greater than 10 mosm/kg H2O, sus-
285–293 mosm/kg          Plasma and urine osmolality are more ondary to dehydration (diarrhea, severe         pect the presence of a low-molecular-
 H2O [mmol/kg H2O]        useful indicators of degree of hydra- burns, vomiting, fever, hyperventila-         weight toxin (alcohol, methanol,
Panic: <240 or            tion than BUN, hematocrit, or serum tion, inadequate water intake, central or       isoprophyl alcohol, ethylene glycol,
 >320 mosm/kg H2O         proteins.                              nephrogenic diabetes insipidus, or           acetone, ethyl ether, paraldehyde, or
                         Serum osmolality can be estimated by osmotic diuresis), hypernatremia with           mannitol), ethanol being the most
Marbled                   the following formula:                 normal hydration (hypothalamic dis-          common. (See p 381 for further
$$                                                               orders, defective osmostat), hyper-          explanation.)
                                                   BUN           natremia with overhydration (iatrogenic    Every 100 mg/dL of ethanol increases




                                                                                                                                                      Osmolality, serum
                                 Osm = 2( Na )+ +
                                                                 or accidental excessive NaCl or              serum osmolality by 22 mosm/kg
                                                    2.8
                                           Gl ucose              NaHCO3 intake), alcohol or other toxic       H2O.
                                        +                        ingestion (see Comments), hyper-           While the osmolal gap may over-
                                              18
                                                                 calcemia; tube feedings. Drugs: corti-       estimate the blood alcohol level, a
                         where Na+ is in meq/L and BUN and       costeroids, mannitol, glycerin.              normal serum osmolality excludes
                          glucose are in mg/dL.                 Decreased in: Pregnancy (third                ethanol intoxication.
                                                                 trimester), hyponatremia with hypov-       Clin Chem 1990;36:2004.
                                                                 olemia (adrenal insufficiency, renal        J Emerg Med 1992;10:129.
                                                                 losses, diarrhea, vomiting, severe         Pharmacotherapy 1993;13:60.
                                                                 burns, peritonitis, pancreatitis), hypo-   Clin Chem 1998;44:1582.
                                                                 natremia with normovolemia, hypo-
                                                                 natremia with hypervolemia
                                                                 (congestive heart failure, cirrhosis,
                                                                 nephrotic syndrome, SIADH, postoper-
                                                                 ative state). Drugs: chlorthalidone,
                                                                 cyclophosphamide, thiazides.
Osmolality, urine        Test measures renal tubular concen-     Increased in: Hypovolemia. Drugs:          With average fluid intake, normal
(Urine Osm)               trating ability.                        anesthetic agents (during surgery),        random urine osmolality is




                                                                                                                                                      Osmolality, urine
                                                                  carbamazepine, chlorpropamide,             100–900 mosm/ kg H2O.
Random:                                                           cyclophosphamide, metolazone,             After 12-hour fluid restriction, normal
 100–900 mosm/kg                                                  vincristine.                               random urine osmolality is
 H2O [mmol/kg H2O]                                               Decreased in: Diabetes insipidus, pri-      >850 mosm/ kg H2O.
                                                                  mary polydipsia, exercise, starvation.    Am J Med 1982;72:308.
Urine container                                                   Drugs: acetohexamide, demeclocy-




                                                                                                                                                                                 Common Laboratory Tests: Selection and Interpretation
$$                                                                cline, glyburide, lithium, tolazamide.
Oxygen, partial pres- Test measures the partial pressure of Increased in: Oxygen therapy.                    % saturation of hemoglobin (SO2) rep-
 sure, whole blood         oxygen (oxygen tension) in arterial   Decreased in: Ventilation/perfusion          resents the oxygen content divided
(Po2)                      blood.                                 mismatching (asthma, COPD, atelecta- by the oxygen carrying capacity of
                          Partial pressure of oxygen is critical  sis, pulmonary embolism, pneumonia,         hemoglobin.
83–108 mm Hg               since it determines (along with hemo- interstitial lung disease, airway obstruc- % saturation on blood gas reports is




                                                                                                                                                      Oxygen, partial pressure
[11.04–14.36 kPa]          globin and blood supply) tissue        tion by foreign body, shock); alveolar      calculated not measured. It is calcu-
                           oxygen supply.                         hypoventilation (kyphoscoliosis, neuro- lated from PO2 and pH using refer-
Heparinized syringe                                               muscular disease, head injury, stroke);     ence oxyhemoglobin dissociation
$$$                                                               right-to-left shunt (congenital heart dis- curves for normal adult hemoglobin
Collect arterial blood in                                         ease). Drugs: barbiturates, opioids.        (lacking methemoglobin, carboxy-
 a heparinized syringe.                                                                                       hemoglobin, etc). At PO2 <60 mm
 Send to laboratory                                                                                           Hg, the oxygen saturation (and con-
 immediately on ice.                                                                                          tent) cannot be reliably estimated
                                                                                                              from the PO2. Therefore, oximetry
                                                                                                              should be used to determine %
                                                                                                              saturation directly.
                                                                                                             JAMA 1990;264:244.
                                                                                                             Am J Clin Pathol 1995;(1 Suppl):579.
                                                                                                             Obstet Gynecol Surv 1998;53:645.




                                                                                                                                                                                 133
                                                                                                                                                                         134
Test /Range/Collection            Physiologic Basis                         Interpretation                             Comments
Parathyroid              PTH is secreted from the parathyroid Increased in: Primary hyperparathy-         PTH results must always be evaluated




                                                                                                                                                                         Pocket Guide to Diagnostic Tests
 hormone, serum           glands. It mobilizes calcium from     roidism, secondary hyperparathy-           in light of concurrent serum calcium
(PTH)                     bone, increases distal renal tubular  roidism due to renal disease, vitamin D    levels.
                          reabsorption of calcium, decreases    deficiency. Drugs: lithium, furosemide,    PTH tests differ in sensitivity and
Intact PTH:               proximal renal tubular reabsorption   phosphates.                                specificity from assay to assay and
 11–54 pg/mL              of phosphorus, and stimulates 1,25- Decreased in: Hypoparathyroidism, sar-       from laboratory to laboratory.
[1.2–5.7 pmol/L]          hydroxy vitamin D synthesis from      coidosis, hyperthyroidism, hypomagne-     Carboxyl terminal antibody measures
 (laboratory-specific)     25-hydroxy vitamin D by renal         semia, malignancy with hypercalcemia,      intact, carboxyl terminal and midmol-
                          1α-hydroxylase.                       non-parathyroid hypercalcemia.             ecule fragments. It is 85% sensitive




                                                                                                                                                   Parathyroid hormone
Marbled                  The “intact” PTH molecule (84 amino                                               and 95% specific for primary hyper-
$$$$                      acids) has a circulating half-life of                                            parathyroidism.
Fasting sample pre-       about 5 minutes.                                                                Amino terminal antibody measures
 ferred; simultaneous    Carboxyl terminal and mid-molecule                                                intact and amino terminal fragments.
 measurement of           fragments make up 90% of circulat-                                               It is about 75% sensitive for hyper-
 serum calcium and        ing PTH. They are biologically in-                                               parathyroidism.
 phosphorus is also       active, cleared by the kidney, and                                              Intact PTH assays are preferred
 required.                have half-lives of about 1–2 hours.                                              because they detect PTH suppression
                         The amino terminal fragment is bio-                                               in nonparathyroid hypercalcemia.
                          logically active and has a half-life                                            Sensitivity of immunometric assays is
                          of 1–2 minutes.                                                                  85–90% for primary hyperparathy-
                         Measurement of PTH by immuno-                                                     roidism.
                          assay depends on the specificity of                                              Endocrinol Metab Clin North Am
                          the antibodies used.                                                             1989;18:647.
                                                                                                          Mayo Clin Proc 1992;67:637.
                                                                                                          Recent Prog Horm Res 1998;53:283.
Parathyroid hormone- Parathyroid hormone-related protein        Increased in: Humoral hypercalcemia   Assays directed at the amino terminal
 related protein         (PTHrP) is a 139- to 173-amino-acid of malignancy (80% of solid tumors).      portion of PTHrP are not influenced
 (PTHrP), plasma         protein with amino terminal homo-                                             by renal failure.
                         logy to parathyroid hormone (PTH).                                           Increases in PTHrP concentrations are
Assay-specific (pmol/L The homology explains the ability of                                             readily detectable with most current
 or undetectable)        PTHrP to bind to the PTH receptor                                             assays in the majority of patients with
                         and have PTH-like effects on bone                                             humoral hypercalcemia of malig-
Tube containing anti-    and kidney. PTHrP induces increased                                           nancy. About 20% of patients with




                                                                                                                                                 Parathyroid hormone-related protein

                                                                                                                                                                                       Common Laboratory Tests: Selection and Interpretation
 coagulant and protease plasma calcium, decreased plasma                                               malignancy and hypercalcemia will
 inhibitors; specimen    phosphorus, and increased urinary                                             have low PTHrP levels because their
 drawn without a         cAMP.                                                                         hypercalcemia is caused by local
 tourniquet.            PTHrP is found in keratinocytes,                                               osteolytic processes.
$$                       fibroblasts, placenta, brain, pituitary                                       N Engl J Med 1990;322:1106.
                         gland, adrenal gland, stomach, liver,                                        West J Med 1990;153:635.
                         testicular Leydig cells, and mam-                                            Clin Chem 1992;38:2171.
                         mary glands. Its physiologic role in                                         Cancer 1994;73:2223.
                         these diverse sites is unknown.
                        PTHrP is secreted by solid malignant
                         tumors (lung, breast, kidney; other
                         squamous tumors) and produces
                         humoral hypercalcemia of
                         malignancy.
                        PTHrP analysis is by immunoradio-
                         metric assay (IRMA). Assay of
                         choice is amino terminal-specific
                         IRMA. Two-site IRMA assays re-
                         quire sample collection in protease
                         inhibitors because serum proteases
                         destroy immunoreactivity.




                                                                                                                                                                                       135
                                                                                                                                                                                         136
Test /Range/Collection             Physiologic Basis                          Interpretation                                Comments
Partial thromboplas-     Patient’s plasma is activated to clot in Increased in: Deficiency of any individ-     PTT is the best test to monitor adequacy




                                                                                                                                                                                         Pocket Guide to Diagnostic Tests
 tin time, activated,     vitro by mixing it with phospholipid     ual coagulation factor except XIII and      of heparin therapy, but it does not reli-
 plasma                   and an activator substance.              VII; presence of nonspecific inhibitors      ably predict the risk of bleeding.
(PTT)                    Test screens the intrinsic coagulation    (eg, lupus anticoagulant), specific fac-    Test is not always abnormal in von
                          pathway and adequacy of all coagu-       tor inhibitors, von Willebrand’s disease    Willebrand’s disease.




                                                                                                                                                           Partial thromboplastin time
25–35 seconds (range      lation factors except XIII and VII.      (PTT may also be normal), hemophilia       Test may be normal in chronic DIC.
 varies)                 PTT is usually abnormal if any factor     A and B, disseminated intravascular        A very common cause of PTT prolon-
Panic: ≥60 seconds        level drops below 30–40% of              coagulation (DIC). Drugs: heparin,          gation is the spurious presence of
 (off heparin)            normal.                                  warfarin.                                   heparin in the plasma sample.
                                                                  Decreased in: Hypercoagulable states,       Sensitivity and degree of prolongation
Blue                                                               DIC.                                        of PTT depend on particular reagents
$$                                                                                                             used.
Fill tube adequately.                                                                                         Therapeutic levels of heparin are best
 Do not contaminate                                                                                            achieved using a weight-based dosing
 specimen with                                                                                                 nomogram with dose adjustment
 heparin.                                                                                                      based on the PTT at 6 hours.
                                                                                                              JAMA 1989;262:2428.
                                                                                                              Ann Intern Med 1993;119:874.
                                                                                                              Thromb Haemost 1995;73:73.
pH, whole blood        pH assesses the acid-base status of   Increased in: Respiratory alkalosis:           The pH of a standing sample decreases
                        blood, an extremely useful measure    hyperventilation (eg, anxiety), sepsis,        because of cellular metabolism.
Arterial: 7.35–7.45     of integrated cardiorespiratory       liver disease, fever, early salicylate        The correction of pH (measured at
Venous: 7.31–7.41       function.                             poisoning, and excessive artificial             37°C), based on the patient’s temper-
                       The essential relationship between     ventilation.                                   ature, is not clinically useful.
Heparinized syringe     pH, PCO2 and bicarbonate (HCO–) is Metabolic alkalosis: Loss of gastric HCl
                                                           3                                                Am J Med 1982;72:496.
$$$                     expressed by the Henderson–           (eg, vomiting), potassium depletion,          Crit Care Nurs 1996;16:89.
Specimen must be col- Hasselbalch equation (at 37 °C):        excessive alkali administration (eg,




                                                                                                                                                          Common Laboratory Tests: Selection and Interpretation
 lected in heparinized                                        bicarbonate, antacids), diuretics,
 syringe and immedi-                        HCO 3  −
                                                              volume depletion.
                            pH = 6.1 + log               
 ately transported on                       Pco 2 × 0.03   Decreased in: Respiratory acidosis:
 ice to lab without                                           decreased alveolar ventilation (eg,
 exposure to air.      Arteriovenous pH difference is         COPD, respiratory depressants), neuro-




                                                                                                                                                     pH
                        0.01–0.03 but is greater in patients  muscular diseases (eg, myasthenia).
                        with congestive heart failure and    Metabolic acidosis (bicarbonate deficit):
                        shock.                                increased formation of acids (eg, ketosis
                                                              [diabetes mellitus, alcohol, starvation],
                                                              lactic acidosis); decreased H+ excretion
                                                              (eg, renal failure, renal tubular acidosis,
                                                              Fanconi’s syndrome); increased acid
                                                              intake (eg, ion-exchange resins, salicy-
                                                              lates, ammonium chloride, ethylene gly-
                                                              col, methanol); and increased loss of
                                                              alkaline body fluids (eg, diarrhea, fistu-
                                                              las, aspiration of gastrointestinal con-
                                                              tents, biliary drainage).




                                                                                                                                                          137
                                                                                                                                                                  138
Test /Range/Collection           Physiologic Basis                             Interpretation                                Comments
Phosphorus, serum        The plasma concentration of in-   Increased in: Renal failure, massive blood trans-       Thrombocytosis may cause spuri-




                                                                                                                                                                  Pocket Guide to Diagnostic Tests
                          organic phosphate is determined fusion, hypoparathyroidism, sarcoidosis, neo-             ous elevation of serum phos-
2.5–4.5 mg/dL             by parathyroid gland function,    plasms, adrenal insufficiency, acromegaly,               phate, but plasma phosphate
[0.8–1.45 mmol/L]         action of vitamin D, intestinal   hypervitaminosis D, osteolytic metastases to            levels are normal.
Panic: <1.0 mg/dL         absorption, renal function, bone  bone, leukemia, milk-alkali syndrome, healing          Clin Lab Med 1993;13:183.
                          metabolism, and nutrition.        bone fractures, pseudohypoparathyroidism, dia-         Ann Pharmacother 1994;28:626.
Marbled                                                     betes mellitus with ketosis, malignant hyper-          Am J Med Sci 1994;307:255.
$                                                           pyrexia, cirrhosis, lactic acidosis, respiratory       J Clin Endocrinol Metab
Avoid hemolysis.                                            acidosis. Drugs: phosphate infusions or enemas,         1998;83:3860.
                                                            anabolic steroids, ergocalciferol, furosemide,
                                                            hydrochlorothiazide, clonidine, verapamil,
                                                            potassium supplements, and others.
                                                           Decreased in: Hyperparathyroidism, hypovitami-
                                                            nosis D (rickets, osteomalacia), malabsorption




                                                                                                                                                     Phosphorus
                                                            (steatorrhea), malnutrition, starvation or cachexia,
                                                            GH deficiency, chronic alcoholism, severe diar-
                                                            rhea, vomiting, nasogastric suction, severe hyper-
                                                            calcemia (any cause), acute gout, osteoblastic
                                                            metastases to bone, severe burns (diuretic phase),
                                                            respiratory alkalosis, hyperalimentation with in-
                                                            adequate phosphate repletion, carbohydrate admi-
                                                            nistration (eg, intravenous D50W glucose bolus),
                                                            renal tubular acidosis and other renal tubular
                                                            defects, diabetic ketoacidosis (during recovery),
                                                            acid-base disturbances, hypokalemia, pregnancy,
                                                            hypothyroidism, hemodialysis. Drugs: acetazo-
                                                            lamide, phosphate-binding antacids, anticonvul-
                                                            sants, beta-adrenergic agonists, catecholamines,
                                                            estrogens, isoniazid, oral contraceptives, pro-
                                                            longed use of thiazides, glucose infusion, insulin
                                                            therapy, salicylates (toxicity).
Platelet aggregation,      Platelet aggregometry can provide Abnormal in: Acquired defects in the platelet          Acquired platelet dysfunction is
 whole blood                information concerning possible release reaction (eg, drugs, following cardio-           more common than the heredi-
                            qualitative platelet defects.       pulmonary bypass, uremia, paraproteinemias,          tary form.
Aggregation by adeno-       Aggregation is measured as an       myeloproliferative disorders), congenital release   Hereditary storage pool disease is
 sine diphosphate           increase in light transmission      abnormalities, Glanzmann’s thrombasthenia            common enough to be suspected
 (ADP), collagen, epi-      through stirred platelet-rich       (absent aggregation to ADP, collagen, epi-           in a child with easy or sponta-
 nephrine, thrombin,        plasma (PRP) when a specific         nephrine), essential athrombia (similar to           neous bruising.
 ristocetin, and arachi-    agonist is added.                   Glanzmann’s disease except clot retraction is       Test should not be done if the




                                                                                                                                                          Platelet aggregation

                                                                                                                                                                                 Common Laboratory Tests: Selection and Interpretation
 donic acid                Test examines platelet aggrega-      normal), storage pool disease (no secondary          patient has taken aspirin within
                            tion response to various agonists wave with ADP, epinephrine, and decreased              the previous 10 days.
Drawn by lab                (eg, ADP, collagen, epinephrine, aggregation with collagen), cyclooxygenase             Direct PRP aggregation by risto-
$$$$                        thrombin, ristocetin, arachidonic and thromboxane synthetase deficiencies                 cetin (1.5 mg/mL) may be normal
Whole blood in citrate      acid).                              (rare hereditary aspirin-like defects),              or abnormal in von Willebrand’s
 is drawn into a plastic   Newer lumiaggregation measures von Willebrand’s disease (normal aggregation               disease (vWD). Because this test
 tube. Platelet-rich        aggregation and simultaneous        with all factors except ristocetin). Drugs:          has limited sensitivity for detec-
 plasma (PRP) is            platelet ATP release—the so-        aspirin (absent aggregation curves to ADP            tion of vWD, it is no longer used
 obtained by centrifug-     called “platelet release reaction.” and epinephrine, collagen, arachidonate).            for that purpose (see instead
 ing at 100 × g for                                                                                                  Bleeding time, p 59, and von
 10–15 minutes.                                                                                                      Willebrand factor protein, p 184).
                                                                                                                    Semin Thromb Hemost
                                                                                                                     1992;18:167.
                                                                                                                    J Clin Invest 1998;101:479.
                                                                                                                    Thromb Haemost 1998;79:211.




                                                                                                                                                                                 139
                                                                                                                                                            140
Test /Range/Collection            Physiologic Basis                         Interpretation                              Comments
Platelet count, whole    Platelets are released from mega-     Increased in: Myeloproliferative dis-        N Engl J Med 1995;332:1132.




                                                                                                                                                            Pocket Guide to Diagnostic Tests
 blood                    karyocytes in bone marrow and are     orders: polycythemia vera, chronic          Am J Med 1995;98:436.
(Plt)                     important for normal hemostasis.      myeloid leukemia, essential thrombo-        Am J Med 1995;98:551.
                         Platelet counting is done by flow       cythemia, myelofibrosis; after bleeding,     J Clin Pathol 1996;49:664.
150–450 × 103/µL          cytometry with size discrimination    postsplenectomy, reactive thrombocy-        Ann Intern Med 1998;129:886.
[× 109/L]                 based on electrical impedance or      tosis secondary to inflammatory dis-         Br J Haematol 1998;100:571.
Panic: <25 × 103/µL       electro-optical systems.              eases, iron deficiency, malignancies,




                                                                                                                                           Platelet count
                                                                alkalosis.
Lavender                                                       Decreased in: Decreased production:
$                                                               bone marrow suppression or replace-
                                                                ment, chemotherapeutic agents, drugs
                                                                (eg, ethanol). Increased destruction or
                                                                removal: splenomegaly, disseminated
                                                                intravascular coagulation, platelet anti-
                                                                bodies (idiopathic thrombocytopenic
                                                                purpura, posttransfusion purpura,
                                                                neonatal isoimmune thrombocytopenia,
                                                                drugs [eg, quinidine, cephalosporins]).
Platelet-associated   Antibody screening involves direct        Positive in: Some autoimmune thrombo-   In ITP, the direct antiplatelet antibody
 IgG, whole blood       testing of a patient’s platelets to      cytopenias (eg, ITP) (90–95%).          test may be useful to confirm the
                        demonstrate platelet-associated IgG                                              diagnosis and monitor subsequent
Negative                (which may be directed against spe-                                              response to therapy. It is also useful
                        cific platelet antigens or may represent                                          in diagnosing posttransfusion purpura
Yellow                  immune complexes nonspecifically                                                  and suspected neonatal isoimmune




                                                                                                                                                   Platelet-associated IgG
$$$$                    absorbed to the platelet surface) in                                             thrombocytopenia.
17 mL of blood is       idiopathic (autoimmune) thrombo-                                                Platelet-associated IgG is also useful




                                                                                                                                                                             Common Laboratory Tests: Selection and Interpretation
 needed.                cytopenic purpura (ITP).                                                         for patients with thrombocytopenia or
                      It also involves indirect testing of the                                           as part of a platelet cross-match prior
                        patient’s serum against a panel of                                               to transfusion of patients who have
                        reagent platelets to detect circulating                                          repeatedly failed to respond to ran-
                        antiplatelet antibodies. In allo-                                                dom donor platelet transfusions.
                        immune thrombocytopenia, the                                                    N Engl J Med 1991;324:27.
                        patient’s direct test is negative and                                           Br J Haematol 1997;96:204.
                        the patient’s serum reacts with
                        reagent platelets.
                      Antibody specificity can be identified,
                        and platelets lacking the involved
                        antigen can be transfused.




                                                                                                                                                                             141
                                                                                                                                                                       142
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Porphobilinogen,         Porphyrias are characterized clinically Positive in: Acute intermittent porphy-   Positive qualitative urinary PBG tests




                                                                                                                                                                       Pocket Guide to Diagnostic Tests
 urine                    by neurologic and cutaneous mani-       ria, variegate porphyria, coproporphy-    should be followed up by quantitative
(PBG)                     festations and chemically by over-      ria, lead poisoning (rare).               measurements. Many labs report
                          production of porphyrin and other      Negative in: 20–30% of patients with       frequent false positives with the
Negative                  precursors of heme production.          hepatic porphyria between attacks.        Watson-Schwartz test.




                                                                                                                                                     Porphobilinogen
                         PBG is a water-soluble precursor of                                               A screening PBG test is insensitive,
$$                        heme whose urinary excretion is                                                   and a negative test does not rule out
Protect from light.       increased in symptomatic hepatic                                                  porphyria between attacks or the
                          porphyrias.                                                                       carrier state.
                         PBG is detected qualitatively by a                                                Specific porphyrias can be better defined
                          color reaction with Ehrlich’s reagent                                             by quantitative measurement of urine
                          and confirmed by extraction into                                                   PBG and by measurement of erythro-
                          chloroform (Watson-Schwartz test).                                                cyte uroporphyrinogen-l-synthetase.
                                                                                                           Mayo Clin Proc 1994;69:289.
                                                                                                           J Inherit Metab Dis 1997;20:237.
                                                                                                           Semin Liver Dis 1998;18:57.
Potassium, serum   Potassium is predominantly an intra- Increased in: Massive hemolysis, severe       Spurious hyperkalemia can occur with
(K+)                cellular cation whose plasma level    tissue damage, rhabdomyolysis, acido-        hemolysis of sample, delayed separa-
                    is regulated by renal excretion.      sis, dehydration, acute or chronic renal     tion of serum from erythrocytes, pro-
3.5–5.0 meq/L      Plasma potassium concentration deter- failure, Addison’s disease, renal tubular     longed fist clenching during blood
 [mmol/L]           mines neuromuscular irritability.     acidosis type IV (hyporeninemic hypo-        drawing, and prolonged tourniquet
Panic: <3.0 or      Elevated or depressed potassium       aldosteronism), hyperkalemic familial        placement. Very high white blood cell
 >6.0 meq/L         concentrations interfere with         periodic paralysis, exercise (transient).    or platelet counts may cause spurious
                    muscle contraction.                   Drugs: potassium salts, potassium-           elevation of serum potassium, but




                                                                                                                                                           Common Laboratory Tests: Selection and Interpretation
Marbled                                                   sparing diuretics (eg, spironolactone,       plasma potassium levels are normal.




                                                                                                                                               Potassium
$                                                         triamterene), non-steroidal anti-           Crit Care Nurs Q 1990;13:34.
Avoid hemolysis.                                          inflammatory drugs, beta-blockers, ACE       Clin Chem 1994;40:1528.
                                                          inhibitors, high-dose trimethoprim-         Clin Chem 1998;44:849.
                                                          sulfamethoxazole.
                                                         Decreased in: Low potassium intake,
                                                          prolonged vomiting or diarrhea, renal
                                                          tubular acidosis types I and II, hyper-
                                                          aldosteronism, Cushing’s syndrome,
                                                          osmotic diuresis (eg, hyperglycemia),
                                                          alkalosis, familial periodic paralysis,
                                                          trauma (transient). Drugs: adrenergic
                                                          agents (isoproterenol), diuretics.




                                                                                                                                                           143
                                                                                                                                                                                144
Test /Range/Collection             Physiologic Basis                          Interpretation                            Comments
Prolactin, serum         Prolactin is a polypeptide hormone       Increased in: Sleep, nursing, nipple     Serum PRL is used primarily in




                                                                                                                                                                                Pocket Guide to Diagnostic Tests
(PRL)                      secreted by the anterior pituitary.     stimulation, exercise, hypoglycemia,     workup of suspected pituitary tumor
                         It functions in the initiation and main- stress, hypothyroidism, pituitary         (60% of pituitary adenomas secrete
< 20 ng/mL [µg/L]          tenance of lactation in the post-       tumors (prolactinomas and others),       PRL). Clinical presentation is usually
                           partum period.                          hypothalamic/pituitary stalk lesions,    amenorrhea and galactorrhea in
Marbled                  PRL secretion is inhibited by hypo-       renal failure. Drugs: phenothiazines,    women and impotence in men. (See




                                                                                                                                                     Prolactin
$$$                        thalamic secretion of dopamine.         haloperidol, reserpine, methyldopa,      Amenorrhea algorithm, p 339.)
                         Prolactin levels increase with renal      estrogens, opiates, cimetidine.         Only 4% of impotence is caused by
                           failure, hypothyroidism, and drugs     Decreased in: Drugs: levodopa.            hyperprolactinemia, and hyper-
                           that are dopamine antagonists.                                                   prolactinemia is rare in the absence
                                                                                                            of low serum testosterone.
                                                                                                           Clin Endocrinol 1996;44:305.
                                                                                                           Ann Intern Med 1998;129:472.
                                                                                                           Clin Endocrinol 1998;48:547.
Prostate-specific         Prostate-specific antigen is a glyco-    Increased in: Prostate carcinoma,         PSA is used to monitor recurrence of
 antigen, serum           protein produced by cells of the pro- benign prostatic hypertrophy (BPH),         treated prostate cancer.
(PSA)                     static ductal epithelium and is         following prostate examination.          Decrease in mortality rates resulting




                                                                                                                                                     Prostate-specific antigen
                          present in the serum of all men. It is Negative in: Metastatic prostate carci-    from use for cancer screening is
0–4 ng/mL [µg/L]          absent from the serum of women.         noma treated with antiandrogen            unproved, and the risks of early ther-
                                                                  therapy, postprostatectomy.               apy are significant. PSA is often
Marbled                                                                                                     increased in BPH, and the predictive
$$$                                                                                                         value of a positive test in healthy
                                                                                                            older men is low.
                                                                                                           PSA replaces the acid phosphatase test.
                                                                                                           Hematol Oncol Clin North Am
                                                                                                            1996;10:346.
                                                                                                           Urology 1998;51:789.
                                                                                                           JAMA 1999;281:1591.
Protein C, plasma   Protein C is a vitamin K-dependent      Decreased in: Congenital deficiency,        Homozygous deficiency of protein C
                     proenzyme synthesized in the liver.     liver disease, cirrhosis (13–25%), war-    (<1% activity) is associated with fatal
71–176%              Following its activation by thrombin, farin use (28–60%), vitamin K defi-           neonatal purpura fulminans and
                     it exerts an anticoagulant effect       ciency, disseminated intravascular         massive venous thrombosis. Hetero-
Blue                 through inactivation of factors Va      coagulation (DIC).                         zygous patients (one in 200–300 of
$$$                  and VIIIa using protein S as cofactor.                                             the population, with levels 25–50%
                    Tests to assay quantitative (antigenic)                                             of normal) may be at risk for venous
                     or functional activity are available.                                              thrombosis.




                                                                                                                                                              Common Laboratory Tests: Selection and Interpretation
                    Deficiency is inherited in an autosomal                                             Interpretation of an abnormally low pro-




                                                                                                                                                  Protein C
                     dominant fashion with incomplete                                                   tein C must be tempered by the clinical
                     penetrance or is acquired. Deficient                                                setting. Anticoagulant therapy, DIC,
                     patients may present with a hyper-                                                 and liver disease must not be present.
                     coagulable state, with recurrent                                                   There is overlap between lower limits
                     thrombophlebitis or pulmonary                                                      of normal values and values found in
                     emboli.                                                                            heterozygotes.
                                                                                                       Kindred with dysfunctional protein C
                                                                                                        of normal quantity have been
                                                                                                        identified.
                                                                                                       N Engl J Med 1986;314:1298.
                                                                                                       Am J Clin Pathol 1993;99:677.
                                                                                                       Thromb Haemost 1997;78:344.




                                                                                                                                                              145
                                                                                                                                                                                 146
Test /Range/Collection             Physiologic Basis                          Interpretation                              Comments
Protein electro-         Electrophoresis of serum will separate   ↑ α1: inflammatory states                  Presence of “spikes” in α2, β2, or γ
                          serum proteins into albumin, α1, α2,




                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
 phoresis, serum                                                   (α1-antiprotease), pregnancy.              regions necessitates the use of
                          β2, and γ fractions. Albumin is the     ↑α2: nephrotic syndrome, inflammatory        immunoelectrophoresis to verify the
Adults:                   principal serum protein (see Albu-       states, oral contraceptives, steroid       presence of a monoclonal gammo-
  Albumin:                min, p 47). The term “globulin” gen-     therapy, hyperthyroidism.                  pathy (see Immunoelectrophoresis,
   3.3–5.7 g/dL           erally refers to the non-albumin        ↑ β: hyperlipidemia, hemoglobinemia,        p 112).
  α1: 0.1–0.4 g/dL        fraction of serum protein.               iron deficiency anemia.                   If Bence Jones proteins (light chains)




                                                                                                                                                       Protein electrophoresis
  α2: 0.3–0.9 g/dL       The α1 fraction contains α1-             ↑ γ polyclonal gammopathies (liver          are suspected, urine protein electro-
  β 2: 0.7–1.5 g/dL       antiprotease (90%), α1-lipoprotein       disease, cirrhosis [associated with        phoresis needs to be done.
  γ: 0.5–1.4 g/dL         and α1-acid glycoprotein. The α2         β–γ “bridging”], chronic infections,     Test is insensitive for detection of
                          fraction contains α2-macroglobulin,      autoimmune disease); monoclonal            decreased levels of immunoglobulins
Marbled                   haptoglobin, and ceruloplasmin.          gammopathies (multiple myeloma,            and α1-antiprotease. Specific quantita-
$$                        The β fraction contains transferrin,     Waldenström’s macroglobulinemia,           tion is required (see Immunoglobulins,
                          hemopexin, complement C3, and            lymphoid malignancies, monoclonal          p 113 and α1-Antiprotease, p 55).
                          β-lipoproteins. The γ fraction con-      gammopathy of undetermined               If plasma is used, fibrinogen will be
                          tains immunoglobulins G, A, D, E,        significance).                             detected in the β–γ region.
                          and M.                                  ↓ α1: α1-antiprotease deficiency.          The “acute-phase protein pattern”
                                                                  ↓ α2: in vivo hemolysis, liver disease.     seen with acute illness, surgery,
                                                                  ↓ γ: hypo-β-lipoproteinemias.               infarction or trauma is characterized
                                                                  ↓ γ: immune deficiency.                      by an ↑α2 (haptoglobin) and ↑α1
                                                                                                              (α1-antiprotease).
                                                                                                            Arch Pathol Lab Med 1999;123:114.
Protein S (antigen),     Protein S is a vitamin K-dependent       Decreased in: Congenital protein S defi-     This test measures antigen and not bio-
 plasma                    glycoprotein, synthesized in the        ciency, liver disease, warfarin therapy,    logic activity. Protein S can also be
                           liver.                                  disseminated intravascular coagulation,     measured in a functional activity
76–178%                  It acts as a cofactor for protein C in    vitamin K deficiency, nephrotic              assay.




                                                                                                                                                        Protein S
                           producing its anticoagulant effect.     syndrome.                                  Ann Intern Med 1987;106:677.
Blue                       Sixty percent of protein S is protein-                                             Thromb Haemost 1997;78:351.
$$$                        bound; only free protein S has anti-                                               Ann Intern Med 1998;128:8.
                           coagulant function.                                                                Thromb Haemost 1998;79:802.




                                                                                                                                                                         Common Laboratory Tests: Selection and Interpretation
                         Deficiency is associated with recur-
                           rent venous thrombosis before the
                           age of 40.
Protein, total, plasma   Plasma protein concentration is deter- Increased in: Polyclonal or monoclonal        Serum total protein consists primarily
 or serum                 mined by nutritional state, hepatic    gammopathies, marked dehydration.             of albumin and globulin.
                          function, renal function, hydration,   Drugs: anabolic steroids, androgens,         Serum globulin level is calculated as
                          and various disease states.                                                          total protein minus albumin.




                                                                                                                                                        Protein, total
6.0–8.0 g/dL                                                     corticosteroids, epinephrine.
[60–80 g/L]              Plasma protein concentration deter-    Decreased in: Protein-losing entero-          Hypoproteinemia usually indicates
                          mines the colloidal osmotic pressure. pathies, acute burns, nephrotic syn-           hypoalbuminemia, since albumin is
Marbled                                                          drome, severe dietary protein deficiency,      the major serum protein.
$                                                                chronic liver disease, malabsorption         Ann Thorac Surg 1999;67:236.
Avoid prolonged                                                  syndrome, agammaglobulinemia.
  venous stasis during
  collection.




                                                                                                                                                                         147
                                                                                                                                                                           148
Test /Range/Collection             Physiologic Basis                         Interpretation                              Comments
Prothrombin time,        PT screens the extrinsic pathway of      Increased in: Liver disease, vitamin K   Routine preoperative measurement of




                                                                                                                                                                           Pocket Guide to Diagnostic Tests
 whole blood               the coagulation system. It is per-      deficiency, intravascular coagulation,    PT is unnecessary unless there is clin-
(PT)                       formed by adding calcium and tissue circulating anticoagulant, massive           ical history of a bleeding disorder.
                           thromboplastin to a sample of cit-      transfusion. Drugs: warfarin.           Efforts to standardize and report the
11–15 seconds              rated, platelet-poor plasma and mea-                                             prothrombin time as an INR (Interna-
Panic: ≥ 30 seconds        suring the time required for fibrin                                               tional Normalized Ratio) depend on
                           clot formation.                                                                  assigning reagents an International
Blue                     It is most sensitive to deficiencies in                                             Sensitivity Index (ISI) so that:
$                          the vitamin K-dependent clotting                                                                               ISI
Fill tube completely.      factors II, VII, IX, and X. It is also                                                           PT patient 
                                                                                                                    INR =                
                           sensitive to deficiencies of factor V.                                                            PT normal 
                           It is insensitive to fibrinogen defi-




                                                                                                                                                        Prothrombin time
                                                                                                           However, assignment of incorrect ISI
                           ciency and not affected by heparin.                                              by reagent manufacturers has caused
                         PT is also used to monitor warfarin                                                a greater lack of standardization.
                           therapy.                                                                        Bleeding has been reported to be three
                         In liver disease, the PT reflects the                                               times more common in patients with
                           hepatic capacity for protein synthe-                                             INRs of 3.0– 4.5 than in patients with
                           sis. PT responds rapidly to altered                                              INRs of 2.0–3.0.
                           hepatic function because the serum                                              PT is quite insensitive to individual
                           half-lives of factors II and VII are                                             decreases in factors VII, IX, and X to
                           short (hours).                                                                   50% of normal but is much more sensi-
                                                                                                            tive to mild deficiencies in two or more
                                                                                                            factors. Thus, patients starting warfarin
                                                                                                            therapy or with liver disease may have
                                                                                                            elevated prothrombin times with no
                                                                                                            significant in vivo coagulation defects.
                                                                                                           JAMA 1989;262:2428.
                                                                                                           J Lab Clin Med 1996;128:214.
                                                                                                           J Clin Pathol 1998;51:356.
Q fever antibody,       Coxiella burnetii is a rickettsial organ- Increased in: Acute or chronic Q fever    Clinical presentation is similar to that
 serum                   ism that is the causative organism for (CF antibodies are present by the sec-       of severe influenza. Typically, there
                         Q fever. Most likely mode of trans-       ond week in 65% of cases and by the       is no rash.
<1 8 titer               mission is inhalation of aerosols         fourth week in 90%; acute and con-       Tests are usually performed in large
                         from exposure to common reser-            valescent titers [IFA or ELISA] detect    reference labs or public health centers.
Marbled                  voirs, sheep and cattle.                  infection with 89–100% sensitivity       Occasionally, titers do not rise for
$$$                     Antibodies to the organism can be          and 100% specificity), and recent          4–6 weeks, especially if antimicrobial
Submit paired sera, one detected by the presence of agglu-         vaccination for Q fever.                  therapy has been given.




                                                                                                                                                                           Common Laboratory Tests: Selection and Interpretation
 collected within        tinins, by complement fixation (CF),                                                Patients with Q fever have a high pre-
 1 week of illness and   by immunofluorescent antibody test-                                                  valence of antiphospholipid antibody
 another 2–3 weeks       ing (IFA), or by ELISA. Agglutinin                                                  (81%), especially as measured by




                                                                                                                                                        Q fever antibody
 later. Avoid            titers are found 5–8 days after infec-                                              lupus anticoagulant test or measure-
 hemolysis.              tion. IgM can be detected at 7 days                                                 ment of antibodies to cardiolipin.
                         (IFA, ELISA) and may persist for up                                                 These tests may be useful in diag-
                         to 32 weeks (ELISA). IgG (IFA,                                                      nosing patients presenting with
                         ELISA) appears after 7 days and                                                     fever alone.
                         peaks at 3–4 weeks.                                                                Recent Q fever vaccination causes a
                        Diagnosis of Q fever is usually con-                                                 rise in antibody titers similar to that
                         firmed by serologic findings of anti-                                                 seen with acute infection.
                         phase II antigen IgM titers of ≥1 50                                               Antibodies to Q fever do not cross-
                         and IgG titers of ≥ 1 200. The find-                                                 react with other rickettsial antibodies.
                         ing of elevated levels of both IgM                                                 Eur J Clin Microbiol Infect Dis
                         and IgA by ELISA has both high                                                      1996;15:749.
                         sensitivity and high specificity for                                                Clin Diag Lab Immunol 1997;4:384.
                         acute Q fever. In chronic Q fever,                                                 Chest 1998;114:808.
                         phase I antibodies, especially IgG                                                 J Clin Microbiol 1998;36:1823.
                         and IgA, are predominant.                                                          Clin Diag Lab Immunol 1999;6:173.




                                                                                                                                                                           149
                                                                                                                                                                        150
Test /Range/Collection            Physiologic Basis                         Interpretation                             Comments
Rapid plasma reagin, Measures nontreponemal antibodies        Increased in: Syphilis: primary (78%), RPR is used as a screening test and in




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
  serum               that are produced when Treponema         secondary (97%), symptomatic late         suspected primary and secondary
(RPR)                 pallidum interacts with host tissue.     (74%). Biologic false-positives occur in syphilis. Since the test lacks speci-




                                                                                                                                                  Rapid plasma reagin
                     The card test is a flocculation test per- a wide variety of conditions, including    ficity, positive tests should be con-
Nonreactive           formed by using a cardiolipin-           leprosy, malaria, intravenous drug        firmed with the FTA-ABS or
                      lecithin-cholesterol carbon-             abuse, aging, infectious mononucleosis, MHA-TP test (see pp 92 and 129,
Marbled               containing antigen reagent mixed on HIV infection (≤ 15%), autoimmune              respectively). RPR titers can be used
$                     a card with the patient’s serum. A       diseases (SLE, rheumatoid arthritis),     to follow serologic response to treat-
                      positive test (presence of antibodies) pregnancy.                                  ment. (See Syphilis test table, Table
                      is indicated when black carbon                                                     8-20, p 391.)
                      clumps produced by flocculation are                                                Ann Intern Med 1991;114:1005.
                      seen by the naked eye.                                                            J Clin Microbiol 1995;33:1829.
                                                                                                        Sex Trans Dis 1998;25:569.
Red cell volume,         Test measures absolute volume of red Increased in: Polycythemia vera, sec-     Test is clinically indicated (but not
 whole blood              cells based on hemodilution of a     ondary polycythemia due to tissue         always required) in the diagnosis of
(RCV)                     known quantity of radioactivity in   hypoxemia (pulmonary disease, con-        polycythemia vera.
                          the circulation.                     genital heart disease, carboxyhemoglo-   Mayo Clin Proc 1991;66:102.
Male: 24–32              Test can distinguish between absolute binemia [cigarette smoking],             Transfusion 1999;39:149.
Female: 22–28 mL/kg       polycythemia (increased hematocrit   methemoglobinemia), or neoplasms         Anesth Analg 1998;87:1234.
                          [Hct], increased RCV) and relative   (renal cell carcinoma, hepatoma, large   J Soc Gynecol Investig 1997;4:254.




                                                                                                                                                Red cell volume
Yellow                    polycythemia (hemoconcentration)     uterine leiomyomas), high altitude,




                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
Lavender (for Hct)        (increased Hct, normal RCV).         pregnancy.
$$$                      Alternative techniques can be used to
A sample of the           measure RCV without exposing the
 patient’s whole blood patient to radiation, including use of
 is labeled with radio-   biotin-, 53Cr-, and sodium
 active 51Cr (which is    fluorescein-labeled red cells.
 taken up into red
 cells) and reinjected
 into the patient. Blood
 is sampled 10 and
 60 minutes later to
 measure radioactivity.




                                                                                                                                                                  151
                                                                                                                                                                              152
Test /Range/Collection              Physiologic Basis                           Interpretation                                Comments
Renin activity, plasma The renal juxtaglomerular apparatus       Increased in: Dehydration, some hyper-         PRA alone is not a satisfactory screening




                                                                                                                                                                              Pocket Guide to Diagnostic Tests
(PRA)                     generates renin, an enzyme that         tensive states (eg, renal artery stenosis);    test for hyperaldosteronism because
                          converts angiotensinogen to             edematous states (cirrhosis, nephrotic         suppressed PRA has only 64% sensi-
High-sodium diet          angiotensin I.                          syndrome, congestive heart failure);           tivity and 83% specificity for primary
 (75–150 meq Na+/d): The inactive angiotensin I is then con- hypokalemic states (gastrointestinal                hyperaldosteronism. However, when
 supine, 0.2–2.3; stand- verted to angiotensin II, which is a     sodium and potassium loss, Bartter’s           plasma aldosterone and PRA testing
 ing, 1.3–4.0 ng/mL/h     potent vasopressor.                     syndrome); adrenal insufficiency,               are combined, the sensitivity for pri-
Low-sodium diet          Renin activity is measured by the abil- chronic renal failure, left ventricular         mary hyperaldosteronism increases to
 (30–75 meq Na   +/d):    ity of patient’s plasma to generate     hypertrophy. Drugs: ACE inhibitors,            95% (see Aldosterone, plasma, p 48).
 standing, 4.0–7.7 ng/    angiotensin I from substrate            estrogen, hydralazine, nifedipine,            Test is also useful in evaluation of
 mL/h                     (angiotensinogen).                      minoxidil, oral contraceptives.                hypoaldosteronism (low-sodium diet,
                         Normal values depend on the patient’s Decreased in: Hyporeninemic hypo-                 patient standing).
Lavender                  hydration, posture, and salt intake.    aldosteronism, some hypertensive              Measurement of peripheral vein renin




                                                                                                                                                             Renin activity
$$                                                                states (eg, primary aldosteronism,             activity is not useful in classification
                                                                  severe preeclampsia). Drugs: beta-             of hypertensive patients or in diagno-
                                                                  blockers, aspirin, clonidine, prazosin,        sis of renal artery stenosis.
                                                                  reserpine, methyldopa, indomethacin.          Bilateral renal vein sampling has been
                                                                                                                 used to investigate renal artery steno-
                                                                                                                 sis. In general, a renal vein renin
                                                                                                                 (RVR) ratio of 1.5 or more (affected/
                                                                                                                 nonaffected side) is predictive of
                                                                                                                 response to revascularization in >90%
                                                                                                                 of cases, but 60% of cases with RVR
                                                                                                                 ratios <1.5 will also respond. Therefore,
                                                                                                                 the test cannot reliably predict thera-
                                                                                                                 peutic response to a surgical procedure.
                                                                                                                Mayo Clin Proc 1994;69:1172.
                                                                                                                Acta Obstet Gynecol Scand
                                                                                                                 1998;77:609.
                                                                                                                J Hum Hypertens 1998;12:455.
                                                                                                                Am J Nephrol 1996;16:471.
Reptilase clotting    Reptilase is an enzyme derived from Increased in: Hypofibrinogenemia,            When the thrombin time is prolonged,
 time, plasma          the venom of Bothrops atrox or         dysfibrinogenemia, afibrinogenemia,        the reptilase time is useful in distin-




                                                                                                                                                 Reptilase clotting time
                       Bothrops jararaca, South American      and disseminated intravascular coagu-    guishing the presence of an anti-
13–19 seconds          pit vipers.                            lation ( DIC).                           thrombin (normal reptilase time)
                      Reptilase cleaves a fibrinopeptide      Normal in: Presence of heparin.           from hypo- or dysfibrinogenemia
Blue                   from fibrinogen directly, bypassing                                              (prolonged reptilase time).
$$                     the heparin-antithrombin system, and                                           The reptilase time is normal when
                       produces a fibrin clot. The reptilase                                            heparin is the cause of a prolonged




                                                                                                                                                                           Common Laboratory Tests: Selection and Interpretation
                       time will be normal in heparin toxic-                                           thrombin time.
                       ity, even when the thrombin time is                                            The reptilase time is only slightly pro-
                       infinite.                                                                        longed by fibrin degradation products.
                                                                                                      Br J Haematol 1971;21:43.
Reticulocyte count,   Reticulocytes are immature red blood Increased in: Hemolytic anemia, blood This test is indicated in the evaluation
 whole blood           cells that contain cytoplasmic mRNA. loss; recovery from iron, B12, or folate  of anemia to distinguish hypoprolifer-
                                                             deficiency or drug-induced anemia.        ative from hemolytic anemia or blood
33–137 × 103/µL                                             Decreased in: Iron deficiency anemia,      loss.




                                                                                                                                                 Reticulocyte count
[× 109/L]                                                    aplastic anemia, anemia of chronic dis- The old method of measuring reticulo-
                                                             ease, megaloblastic anemia, sideroblas- cytes (manual staining and counting)
Lavender                                                     tic anemia, bone marrow suppression.     has poor reproducibility. It has been
$                                                                                                     replaced by automated methods (eg,
                                                                                                      flow cytometry), which are more pre-
                                                                                                      cise. Method-specific reference
                                                                                                      ranges must be used.
                                                                                                     Am J Hematol 1990;33:13.
                                                                                                     Am J Clin Pathol 1994;102:623.
                                                                                                     Clin Lab Haematol 1996;18(Suppl 1):1




                                                                                                                                                                           153
                                                                                                                                                                154
Test /Range/Collection            Physiologic Basis                        Interpretation                             Comments
Rh grouping, red cells The Rhesus blood group system is sec- Sixty percent of US whites are Rh(D)-      Of D− persons receiving a single D+




                                                                                                                                                                Pocket Guide to Diagnostic Tests
(Rh)                     ond in importance only to the ABO      positive, 40% negative; 72% of African- unit, 50–75% will develop anti-D.
                         system. Anti-Rh antibodies are the     Americans are Rh(D)-positive, 28%        The blood of all donors and recipients
Red                      leading cause of hemolytic disease     negative; 95% of Asian-Americans are     is therefore routinely tested for D,
$                        of the newborn and may also cause      Rh(D)-positive, 5% negative.             so that D− recipients can be given
Proper identification of hemolytic transfusion reactions.                                                 D− blood. Donor bloods must also be
  specimen is critical. Although there are other Rhesus anti-                                            tested for a weak form of D antigen,
                         gens, only tests for the D antigen are                                          called Du, and must be labeled D+ if
                         performed routinely in pretransfu-                                              the Du test is positive. Recipient




                                                                                                                                                  Rh grouping
                         sion testing, since the D antigen is                                            blood need not be tested for Du.
                         the most immunogenic.                                                          Technical Manual of the American
                        The terms Rh-positive and -negative                                              Association of Blood Banks, 11th ed.
                         refer to the presence or absence of                                             American Association of Blood
                         the red cell antigen, D, on the cell                                            Banks, 1993.
                         surface.
                        Persons whose red cells lack D do not
                         regularly have anti-D in their serum.
                        Formation of anti-D almost always
                         results from exposure through trans-
                         fusion or pregnancy to red cells
                         possessing the D antigen.
Rheumatoid factor,   Rheumatoid factor consists of hetero-   Positive in: Rheumatoid arthritis           Rheumatoid factor can be useful in dif-
 serum                geneous autoantibodies usually of       (75–90%), Sjögren’s syndrome                ferentiating rheumatoid arthritis from
(RF)                  the IgM class that react against the    (80–90%), scleroderma, derma-               other chronic inflammatory arthri-
                      Fc region of human IgG.                 tomyositis, SLE (30%), sarcoidosis,         tides. However, a positive RF test is
Negative (<1 16)                                              Waldenström’s macroglobulinemia.            only one of several criteria needed to




                                                                                                                                                     Rheumatoid factor
                                                              Drugs: methyldopa, others.                  make the diagnosis of rheumatoid
Marbled                                                      Low-titer RF can be found in healthy         arthritis.
$                                                             older patients (20%), in 1– 4% of nor-     (See also Autoantibodies table, p 367.)




                                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
                                                              mal individuals, and in a variety of       RF must be ordered selectively because
                                                              acute immune responses (eg, viral           its predictive value is low (34%) if it
                                                              infections, including infectious            is used as a screening test.
                                                              mononucleosis and viral hepatitis),        The test has poor positive predictive
                                                              chronic bacterial infections (tuberculo-    value because of its lack of specificity.
                                                              sis, leprosy, subacute infective endo-      The subset of patients with seronega-
                                                              carditis), and chronic active hepatitis.    tive rheumatic disease limits its sensi-
                                                                                                          tivity and negative predictive value.
                                                                                                         Arch Intern Med 1992;152:2417.
Ribonucleoprotein    This is an antibody to a                Increased in: Scleroderma (20–30%           A negative test essentially excludes




                                                                                                                                                     Ribonucleoprotein antibody
 antibody, serum      ribonucleoprotein-extractable           sensitivity, low specificity), mixed         MCTD.
(RNP)                 nuclear antigen.                        connective tissue disease (MCTD)           (See also Autoantibodies table, p 367.)
                                                              (95–100% sensitivity, low specificity),     Rheum Dis Clin North Am
Negative                                                      SLE (30%), Sjögren’s syndrome,              1992;18:283.
                                                              rheumatoid arthritis (10%), discoid        Rheum Dis Clin North Am
Marbled                                                       lupus (20–30%).                             1992;18:311.
$$                                                                                                       Rheum Dis Clin North Am
                                                                                                          1994;20:29.




                                                                                                                                                                                  155
                                                                                                                                                                        156
Test /Range/Collection            Physiologic Basis                         Interpretation                              Comments
Rubella antibody,        Rubella (German measles) is a viral    Increased in: Recent rubella infection,    Rubella titers of ≤1 8 indicate suscep-




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
 serum                    infection that causes fever, malaise,  congenital rubella infection, previous     tibility and need for immunization to
                          coryza, lymphadenopathy, fine           rubella infection or vaccination (immu-    prevent infection during pregnancy.
<1 8 titer                maculopapular rash, and congenital     nity). Spuriously increased IgM anti-      Titers of >1 32 indicate immunity
                          birth defects when infection occurs    body occurs in the presence of             from prior infection or vaccination.
Marbled                   in utero.                              rheumatoid factor.                        Definitive diagnosis is based on a four-
$                        Antibodies to rubella can be detected                                              fold rise in titer or the presence of
For diagnosis of a re-    by hemagglutination inhibition (HI),                                              IgM antibody.




                                                                                                                                                     Rubella antibody
  cent infection, submit complement fixation (CF), indirect                                                 To diagnose congenital infection, sub-
  paired sera, one col-   hemagglutination (IHA), ELISA, or                                                 mit a single specimen for IgM. If
  lected within 1 week    latex agglutination (LA). Tests can                                               positive, submit a second specimen
  of illness and another detect IgG and IgM antibody.                                                       2–3 months later to rule out maternal
  2–4 weeks later.       Titers usually appear as rash fades                                                antibody transmission across the
                          (1 week) and peak at 10–14 days for                                               placenta.
                          HI and 2–3 weeks for other tech-                                                 The recent resurgence of congenital
                          niques. Baseline titers may                                                       rubella can largely be prevented with
                          remain elevated for life.                                                         improved rubella testing and
                                                                                                            vaccination programs.
                                                                                                           Rev Infect Dis 1985;7(Suppl 1):S108.
                                                                                                           Am J Clin Pathol 1996;106:170.
                                                                                                           J Infect Dis 1997;175:749.
Russell’s viper venom Russell viper venom is extracted from Increased in: Circulating lupus antico-      The lupus anticoagulant may be asso-
 clotting time (dilute), a pit viper (Vipera russelli), which is agulants (LAC), severe fibrinogen defi-    ciated with a prolonged PTT and a
 plasma                   common in Southeast Asia (espe-        ciency (< 50 mg/dL), deficiencies in      positive inhibitor screen (mixing
(RVVT)                    cially Burma) and which causes a       prothrombin, factor V, factor X, and     study). If heparin is not present, a
                          rapidly fatal syndrome of consump-     heparin therapy.                         dilute Russell viper venom test may




                                                                                                                                                   Russell’s viper venom clotting time
24–37 seconds             tive coagulopathy with hemorrhage, Normal in: Factor VII deficiency and all      be indicated to confirm that the
                          shock, rhabdomyolysis, and renal       intrinsic pathway factor deficiencies.    inhibitor is an LAC.
Blue                      failure.                                                                       Since specific factor inhibitors against




                                                                                                                                                                                         Common Laboratory Tests: Selection and Interpretation
$$                       Approximately 70% of the protein                                                 factors VIII and IX are associated
                          content of the venom is phospholi-                                              with clinically significant bleeding
                          pase A2, which activates factor X in                                            and require specific treatment, they
                          the presence of phospholipid,                                                   must not be missed.
                          bypassing factor VII.                                                          The LAC is associated with an in-
                         RVVT is a phospholipid-dependent                                                 creased risk of thrombosis (venous >
                          coagulation test used in detection of                                           arterial), recurrent spontaneous abor-
                          antiphospholipid antibodies (so-                                                tion, and the primary antiphospho-
                          called lupus anticoagulants). It                                                lipid syndrome of arterial thrombosis.
                          should be noted that the anticoagu-                                            Haemostasis 1990;20:208.
                          lant detected in vitro may be associ-                                          Blood Coagul Fibrinolysis 1990;1:627.
                          ated with thrombosis (and not                                                  Int J Biochem 1994;26:79.
                          bleeding) in vivo.                                                             Blood Coagul Fibrinolysis 1996;7:31.
                                                                                                         Thromb Res 1997;85:427.




                                                                                                                                                                                         157
                                                                                                                                                                                      158
Test /Range/Collection             Physiologic Basis                         Interpretation                            Comments
Salicylate, serum        At high concentrations, salicylate      Increased in: Acute or chronic salicy-   The potential toxicity of salicylate




                                                                                                                                                                                      Pocket Guide to Diagnostic Tests
(aspirin)                 stimulates hyperventilation, uncou-     late intoxication.                       levels after acute ingestion can be
                          ples oxidative phosphorylation, and                                              determined by using the Salicylate
20–30 mg/dL               impairs glucose and fatty acid                                                   nomogram, p 360. Nomograms have




                                                                                                                                                    Salicylate
[200–300 mg/L]            metabolism. Salicylate toxicity is                                               become less valid with the increasing
Panic: >35 mg/dL          thus marked by respiratory alkalosis                                             popularity of enteric-coated slow-
                          and metabolic acidosis.                                                          release aspirin preparations.
Marbled                                                                                                   Pediatrics 1960;26:800.
$$                                                                                                        Ann Pharmacother 1996;30:935.
                                                                                                          Am J Emerg Med 1996;14:443.
Scleroderma-             This antibody reacts with a cellular    Increased in: Scleroderma (15–20%        Predictive value of a positive test is




                                                                                                                                                    Scleroderma-associated antibody
 associated antibody      antigen (DNA topoisomerase 1) that      sensitivity, high specificity).           >95% for scleroderma. Test has prog-
 (Scl-70 antibody),       is responsible for the relaxation of                                             nostic significance for severe digital
 serum                    supercoiled DNA.                                                                 ischemia in patients with Raynaud’s
                                                                                                           disease and scleroderma.
Negative                                                                                                  (See also Autoantibodies table, p 367.)
                                                                                                          Rheum Dis Clin North Am
Marbled                                                                                                    1990;16:169.
$$                                                                                                        J Rheumatol 1991;18:1826.
                                                                                                          Rheum Dis Clin North Am
                                                                                                           1992;18:483.
                                                                                                          Ann Rheum Dis 1994;53:540.
                                                                                                          Am J Med 1997;103:242.
Semen analysis, ejacu- Sperm are viewed under the micro-        Decreased in: Primary or secondary tes- A low sperm count should be confirmed
 late                   scope for motility and morphology.       ticular failure, cryptorchidism, follow-  by sending two other appropriately
                       Infertility can be associated with low    ing vasectomy, drugs.                     collected semen specimens for
Sperm count: >20 ×      counts or with sperm of abnormal                                                   evaluation.
 106/mL [109/L]         morphology or decreased motility.                                                 Functional and computer-assisted sperm
Motility score:                                                                                            analyses increase diagnostic accuracy
 >60% motile                                                                                               but are not yet widely available.
Volume: 2–5 mL                                                                                            Endocrinol Metab Clin North Am




                                                                                                                                                     Semen analysis

                                                                                                                                                                                Common Laboratory Tests: Selection and Interpretation
Normal morphology:                                                                                         1994;23:725.
 >60%                                                                                                     J Androl 1996;17:718.
                                                                                                          Int J Androl 1997;20:201.
$$                                                                                                        Fertil Steril 1997;67:1156.
Semen is collected in a
 urine container after
 masturbation follow-
 ing 3 days of absti-
 nence from ejacu-
 lation. Specimen
 must be examined
 promptly.
Smith (anti-Sm)           This antibody to Smith antigen (an    Positive in: SLE (30– 40% sensitivity,   A positive test substantially increases




                                                                                                                                                     Smith (anti-Sm) antibody
 antibody, serum           extractable nuclear antigen) is a     high specificity).                        posttest probability of SLE. Test rarely
                           marker antibody for SLE.                                                       needed for the diagnosis of SLE.
Negative                                                                                                 (See also Autoantibodies table, p 367.)
                                                                                                         Clin Rheumatol 1990;9:346.
Marbled                                                                                                  Rheum Dis Clin North Am
$$                                                                                                        1992:18:311.
                                                                                                         Clin Rheumatol 1993;12:350.
                                                                                                         Arthritis Rheum 1996;39:1055.
                                                                                                         J Rheumatol 1998;25:1743.




                                                                                                                                                                                159
                                                                                                                                                                                 160
Test /Range/Collection             Physiologic Basis                          Interpretation                               Comments
Smooth muscle anti-      Antibodies against smooth muscle        Positive in: Autoimmune chronic active       The presence of high titers of smooth




                                                                                                                                                      Smooth muscle antibodies

                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
 bodies, serum            proteins are found in patients with     hepatitis (40–70%, predominantly IgG         muscle antibodies (>1 80) is useful
                          chronic active hepatitis and primary    antibodies), lower titers in primary bil-    in distinguishing autoimmune chronic
Negative                  biliary cirrhosis.                      iary cirrhosis (50%, predominantly IgM       active hepatitis from other forms of
                                                                  antibodies), viral hepatitis, infectious     hepatitis.
Marbled                                                           mononucleosis, cryptogenic cirrhosis        Gut 1980;21:878.
$$                                                                (28%), HIV infection, vitiligo (25%),       J Clin Pathol 1991;44:64.
                                                                  endometriosis, Behçet’s disease (< 2%       Br J Obstet Gynaecol 1991;98:680.
                                                                  of normal individuals).                     J Dermatol 1993;20:679.
Sodium, serum    Sodium is the predominant extracellu- Increased in: Dehydration (excessive         Spurious hyponatremia may be pro-
(Na+)             lar cation. The serum sodium level is sweating, severe vomiting or diarrhea),      duced by severe lipemia or hyper-
                  primarily determined by the volume     polyuria (diabetes mellitus, diabetes       proteinemia if sodium analysis
135—145 meq/L     status of the individual. Hypo-        insipidus), hyperaldosteronism, inade-      involves a dilution step.
 [mmol/L]         natremia can be divided into hypo-     quate water intake (coma, hypothala-       The serum sodium falls about 1.6 meq/L
Panic: <125 or    volemia, euvolemia, and                mic disease). Drugs: steroids, licorice,    for each 100 mg/dL increase in blood
 >155 meq/L       hypervolemia categories. (See          oral contraceptives.                        glucose.
                  Hyponatremia algorithm, p 350.)       Decreased in: Congestive heart failure,     Hyponatremia in a normovolemic




                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
Marbled                                                  cirrhosis, vomiting, diarrhea, excessive    patient with urine osmolality higher
$                                                        sweating (with replacement of water         than plasma osmolality suggests the
                                                         but not salt), salt-losing nephropathy,     possibility of SIADH, myxedema,




                                                                                                                                             Sodium
                                                         adrenal insufficiency, nephrotic syn-        hypopituitarism, or reset osmostat.
                                                         drome, water intoxication, SIADH.          Treatment of disorders of sodium bal-
                                                         Drugs: thiazides, diuretics, ACE in-        ance relies on clinical assessment of
                                                         hibitors, chlorpropamide, carbama-          the patient’s extracellular fluid vol-
                                                         zepine, antidepressants (selective          ume rather than the serum sodium.
                                                         serotonin reuptake inhibitors), anti-      Sodium is commonly measured by
                                                         psychotics.                                 ion-selective electrode.
                                                                                                    Am J Med 1982;72:496.
                                                                                                    Ann Intern Med 1985;102:164.
                                                                                                    Postgrad Med 1993;93:227.
                                                                                                    Med Clin North Am 1997;81:585.
                                                                                                    Hepatology 1998;28:851.
                                                                                                    Am J Med 1999;106:399.




                                                                                                                                                      161
                                                                                                                                                                     162
Test /Range/Collection             Physiologic Basis                         Interpretation                             Comments
Somatomedin C,           Somatomedin C is a growth hormone- Increased in: Acromegaly (level corre- A normal somatomedin C level in chil-




                                                                                                                                                                     Pocket Guide to Diagnostic Tests
 plasma                   dependent plasma peptide produced        lates with disease activity better than  dren is strong evidence that GH defi-
                          by the liver. It is believed to mediate GH level).                                ciency is not present and precludes
123–463 ng/mL (age-       the growth-promoting effect of          Decreased in: Pituitary dwarfism,          the need for extensive pituitary func-
 and sex-dependent)       growth hormone (GH). It has an ana- hypopituitarism, Laron dwarfism (end- tion testing.
                          bolic, insulin-like action on fat and    organ resistance to GH), fasting for    A low level does not prove that GH
Lavender                  muscle and stimulates collagen and       5–6 days, poor nutrition, hypothy-       deficiency is present, since levels may




                                                                                                                                                     Somatomedin C
$$$$                      protein synthesis. Its level is rela-    roidism, cirrhosis. Values may be        be reduced in malnutrition, malab-
                          tively constant throughout the day.      normal in growth hormone-deficient        sorption, chronic systemic illness,
                                                                   patients with hyperprolactinemia or      and hypothyroidism.
                                                                   craniopharyngioma.                      Reference range here is for an immuno-
                                                                                                            assay done following displacement of
                                                                                                            somatomedin C from its binding pro-
                                                                                                            tein (acid-ethanol extraction).
                                                                                                           N Engl J Med 1979;301:1138.
                                                                                                           J Pediatr 1981;99:720.
                                                                                                           J Clin Endocrinol 1988;66:538.
                                                                                                           Endocrinol Metab Clin North Am
                                                                                                            1992;21:649.
SS-A/Ro antibody,   Antibodies to Ro (SSA) cellular        Increased in: Sjögren’s (60–70% sensi- Useful in counseling women of child-
 serum               ribonucleoprotein complexes are        tivity, low specificity), SLE (30–40%), bearing age with known connective
                     found in connective tissue diseases    RA (10%), subacute cutaneous lupus,     tissue disease, since a positive test is
Negative             such as Sjögren’s syndrome (SS),       vasculitis.                             associated with a small but real risk
                     SLE, rheumatoid arthritis (RA),                                                of neonatal SLE and congenital heart
Marbled              and vasculitis.                                                                block. The few (< 10%) patients with




                                                                                                                                               SS-A/Ro antibody
$$                                                                                                  SLE who do not have a positive ANA
                                                                                                    commonly have antibodies to SS-A.




                                                                                                                                                                  Common Laboratory Tests: Selection and Interpretation
                                                                                                   (See also Autoantibodies table, p 367.)
                                                                                                   Medicine 1995;74:109.
                                                                                                   J Rheumatol 1996;23:1897.
                                                                                                   J Am Acad Dermatol 1996;35
                                                                                                    (2 Part 1):147.
                                                                                                   J Autoimmun 1998;11:29.
                                                                                                   Br J Dermatol 1998;138:114.
                                                                                                   Clin Exper Rheumatol
                                                                                                    1999;17:63,130.
SS-B/La antibody,   Antibodies to La (SSB) cellular        Increased in: Sjögren’s (50% sensitiv-    Direct pathogenicity and usefulness of




                                                                                                                                               SS-B/La antibody
 serum               ribonucleoprotein complexes are        ity, higher specificity than anti-SSA),    autoantibody test in predicting dis-
                     found in Sjögren’s syndrome (SS)       SLE (10%).                                ease exacerbation not proved.
Negative             and appear to be relatively more spe-                                           (See also Autoantibodies table, p 367.)
                     cific for SS than are antibodies to                                              Arthritis Rheum 1996;39:1055.
Marbled              SSA. They are quantitated by                                                    Ann Rheum Dis 1997;156:272.
$$                   immunoassay.                                                                    J Autoimmun 1998;11:29.
                                                                                                     Clin Exper Rheumatol 1999;17:130.




                                                                                                                                                                  163
                                                                                                                                                                                              164
Test /Range/Collection             Physiologic Basis                           Interpretation                               Comments
T cell receptor gene     In general, the percentage of T lympho- Positive test results may be seen in T cell   Samples with >10% of cells showing a




                                                                                                                                                         T cell receptor gene rearrangement

                                                                                                                                                                                              Pocket Guide to Diagnostic Tests
 rearrangement            cytes with identical T cell receptors is neoplasms such as T cell lymphocytic         given T cell rearrangement are consid-
Whole blood, bone         very low; in malignancies, however,      leukemia and cutaneous or nodal T cell       ered positive. However, a large mono-
 marrow, or frozen        the clonal expansion of one popula-      lymphomas.                                   clonal population is not absolutely
 tissue                   tion leads to a large number of cells                                                 diagnostic of malignancy.
                          with identical T cell receptor gene re-                                              Am J Hematol 1996;52:171.
Lavender                  arrangement. Southern blot is used to                                                Mol Pathol 1997;50:77.
$$$$                      identify a monoclonal population.                                                    Arch Dermatol 1998;134:15.
                                                                                                               J Am Acad Dermatol 1998;39
                                                                                                                (4 Part 1):554.
                                                                                                               Leukemia 1998;12:1081.
Testosterone, serum     Testosterone is the principal male sex Increased in: Idiopathic sexual precoc-     Serum testosterone levels decrease in
                         hormone, produced by the Leydig         ity (in boys, levels may be in adult       men after age 50.
Males: 3.0–10.0          cells of the testes. Dehydroepiandro- range), adrenal hyperplasia (boys),         A free testosterone level is indicated
Females:                 sterone (DHEA) is produced in the       adrenocortical tumors, trophoblastic       when a normal total testosterone
 0.3–0.7 ng/mL           adrenal cortex, testes and ovaries and disease during pregnancy, idiopathic        level is thought not to reflect free
[Males: 10–35            is the main precursor for serum         hirsutism, virilizing ovarian tumors,      testosterone levels because of
Females:                 testosterone in women. In normal        arrhenoblastoma, virilizing luteoma,       increases in SHBG.




                                                                                                                                                     Testosterone
 1.0–2.4 nmol/L]         males after puberty, the testosterone   testicular feminization (normal or mod-   In men, there is a small diurnal varia-




                                                                                                                                                                     Common Laboratory Tests: Selection and Interpretation
                         level is twice as high as all andro-    erately elevated), cirrhosis (through      tion in serum testosterone with a 20%
Marbled                  gens in females.                        increased SHBG), hyperthyroidism.          elevation in levels in the evenings.
$$$                     In serum, it is largely bound to albu-   Drugs: anticonvulsants, barbiturates,     Endocrinol Metab Clin North Am
                         min (38%) and to a specific steroid      estrogens, oral contraceptives (through    1992;21:921.
                         hormone-binding globulin (SHBG)         increased SHBG).                          Endocrinol Metab Clin North Am
                         (60%), but it is the free hormone      Decreased in: Hypogonadism (primary         1994;23:709.
                         (2%) that is physiologically active.    and secondary, orchidectomy, Klinefel-    Fertil Steril 1998;69:286.
                        The total testosterone level measures    ter’s, uremia, hemodialysis, hepatic      Arch Androl 1998;40:153.
                         both bound and free testosterone in     insufficiency, ethanol [men]). Drugs:      Ann Intern Med 1999;130(4 Part 1):270.
                         the serum (by immunoassay).             digoxin, spironolactone, acarbose.
Thrombin time,          Prolongation of the thrombin time      Increased in: Low fibrinogen               Thrombin time can be used to monitor
 plasma                  indicates a defect in conversion of    (<50 mg/dL), abnormal fibrinogen           fibrinolytic therapy and to screen for




                                                                                                                                                     Thrombin time
                         fibrinogen to fibrin.                    (dysfibrinogenemia), increased fibrin       dysfibrinogenemia or circulating anti-
24–35 seconds                                                   degradation products (eg, disseminated coagulants.
 (laboratory-specific)                                           intravascular coagulation), heparin, fib- Blood 1991;77:2637.
                                                                rinolytic agents (streptokinase, uro-
Blue                                                            kinase, tissue plasminogen activator),
$                                                               primary systemic amyloidosis (40%).




                                                                                                                                                                     165
                                                                                                                                                                          166
Test /Range/Collection            Physiologic Basis                        Interpretation                            Comments
Thyroglobulin, serum Thyroglobulin is a large protein spe- Increased in: Hyperthyroidism, sub-       Thyroglobulin is useful to follow




                                                                                                                                                                          Pocket Guide to Diagnostic Tests
                      cific to the thyroid gland from which acute thyroiditis, untreated thyroid car- patients after treatment of non-
3– 42 ng/mL [µg/L]    thyroxine is synthesized and cleaved. cinomas (except medullary carcinoma): medullary thyroid carcinomas. Levels
                      Highly sensitive immunoradiometric follicular cancer (sensitivity 72%,          fall after successful therapy and rise
Marbled               assays (IRMAs) have minimal inter- specificity 81%), Hürthle cell cancer         when metastases develop.
$$$                   ference from autoantibodies.           (sensitivity 56%, specificity 84%).      Sensitivity of the test is increased if
                                                            Decreased in: Factitious hyperthyroid-    patients are off thyroid replacement for




                                                                                                                                                 Thyroglobulin
                                                             ism, presence of thyroglobulin auto-     6 weeks prior to testing or if given T3
                                                             antibodies, after (>25 days) total       (Cytomel) for the first 4 weeks, then
                                                             thyroidectomy.                           no medication for the last 2 weeks.
                                                                                                     Athyrotic patients on T4 (levothyrox-
                                                                                                      ine) should have values <5 ng/mL
                                                                                                      and those off T4 should have
                                                                                                      values <10 ng/mL.
                                                                                                     Clin Chem 1996;42:164.
                                                                                                     Clin Chem 1996;42:258.
                                                                                                     Eur J Nucl Med 1997;24:722.
                                                                                                     Eur J Surg Oncol 1998;24:553.
                                                                                                     Eur J Endocrinol 1998;138:249.
Thyroglobulin         Antibodies against thyroglobulin are Increased in: Hashimoto’s thyroiditis   The antithyroid peroxidase antibody




                                                                                                                                                 Thyroglobulin antibody
 antibody, serum       produced in autoimmune diseases of (>90%), thyroid carcinoma (45%), thy- test is more sensitive than the thyro-
                       the thyroid and other organs.         rotoxicosis, pernicious anemia (50%),  globulin antibody test in autoimmune
<1 10 (highly method- Ten percent of the normal population   SLE (20%), subacute thyroiditis,       thyroid disease.
 dependent)            have slightly elevated titers (espe-  Graves’ disease.                      There is little indication for this test.
                       cially women and the elderly).       Not Increased in: Multinodular goiter,  (See Thyroid Peroxidase Antibody,
Marbled                                                      thyroid adenomas, and some             below.)
$$                                                           carcinomas.                           Am J Med 1983;74:941.
                                                                                                   Med Clin North Am 1991;75:1.
                                                                                                   J Clin Endocrinol Metab 1998;83:1121.
Thyroperoxidase    Thyroperoxidase (TPO) is a membrane- Increased in: Hashimoto’s thyroiditis       Thyroperoxidase antibody is an anti-
 antibody, serum    bound glycoprotein. This enzyme        (>99%), idiopathic myxedema (>99%), body to the main autoantigenic com-
                    mediates the oxidation of iodide ions  Graves’ disease (75–85%), Addison’s       ponent of microsomes and is a more




                                                                                                                                            Thyroperoxidase antibody
Negative            and incorporation of iodine into tyro- disease (50%), and Riedel’s thyroiditis. sensitive and specific test than
                    sine residues of thyroglobulin. Its    Low titers are present in approximately hemagglutination assays for micro-
Marbled             synthesis is stimulated by thyroid-    10% of normal individuals and patients somal antibodies in the diagnosis of
$$                  stimulating hormone (TSH). TPO is      with nonimmune thyroid disease.           autoimmune thyroid disease. Thyro-
                    the major antigen involved in thyroid                                            peroxidase antibody testing alone is




                                                                                                                                                                       Common Laboratory Tests: Selection and Interpretation
                    antibody-dependent cell-mediated                                                 almost always sufficient to detect
                    cytotoxicity. Antithyroperoxidase                                                autoimmune thyroid disease.
                    antibody assays are performed by                                                J Clin Endocrinol Metab 1990;71:661.
                    ELISA or radioimmunoassay.                                                      Arch Intern Med 1993;153:862.
                                                                                                    J Clin Endocrinol Metab
                                                                                                     1996;81:2595.
                                                                                                    Thyroid 1997;7:471.




                                                                                                                                                                       167
                                                                                                                                                                                     168
Test /Range/Collection             Physiologic Basis                          Interpretation                             Comments
Thyroid-stimulating      TSH is an anterior pituitary hormone Increased in: Hypothyroidism. Mild           Newer sensitive assays can detect low




                                                                                                                                                                                     Pocket Guide to Diagnostic Tests
 hormone, serum           that stimulates the thyroid gland to    increases in recovery phase of acute      enough levels of TSH to be useful in
(TSH; thyrotropin)        produce thyroid hormones.               illness.                                  the diagnosis of hyperthyroidism as
                         Secretion is stimulated by thyrotropin- Decreased in: Hyperthyroidism, acute       well as hypothyroidism and in distin-
0.4–6 µU/mL [mU/L]




                                                                                                                                                       Thyroid-stimulating hormone
                          releasing hormone from the hypo-        medical or surgical illness, pituitary    guishing hyperthyroidism from sub-
                          thalamus. There is negative feedback hypothyroidism. Drugs: dopamine,             normal TSH values occasionally
Marbled                   on TSH secretion by circulating         high-dose corticosteroids.                found in euthyroid sick patients.
$$                        thyroid hormone.                                                                 (See also Thyroid function table, p 393.)
                                                                                                           Test is useful for following patients
                                                                                                            taking thyroid medication.
                                                                                                           Neonatal and cord blood levels are
                                                                                                            2– 4 times higher than adult levels.
                                                                                                           J Nucl Med 1985;26:1248.
                                                                                                           Endocrinol Metab Clin North Am
                                                                                                            1992;21:903.
                                                                                                           Postgrad Med 1993;94:81.
                                                                                                           Clin Chem 1996;42:140.
                                                                                                           Clin Chem 1997;43:2428.
                                                                                                           J R Soc Med 1997;90:547.
                        Test detects heterogeneous IgG anti- Increased in: Graves’ disease.               Although TSH-R [stim] Ab is a marker




                                                                                                                                                      Thyroid-stimulating hormone receptor antibody
Thyroid-stimulating
 hormone receptor        bodies directed against the TSH                                                   of Graves’ disease, the test is not nec-
 antibody, serum         receptor on thyroid cells. Frequently,                                            essary for the diagnosis in most cases.
(TSH-R [stim] Ab)        they cause excess release of hormone                                             Test is very rarely indicated but may
                         from the thyroid.                                                                 be helpful in (1) pregnant women
< 130% basal activity   Test measures antibodies indirectly by                                             with a history of Graves’ disease,
 of adenylyl cyclase     their stimulation of adenylyl cyclase                                             because TSH-R [stim] Ab may have
                         to produce cAMP.                                                                  some predictive value for neonatal




                                                                                                                                                                                                      Common Laboratory Tests: Selection and Interpretation
Marbled                                                                                                    thyrotoxicosis; (2) patients presenting
$$$$                                                                                                       with exophthalmos who are euthy-
                                                                                                           roid, to confirm Graves’ disease.
                                                                                                          Use of the test to predict relapse of
                                                                                                           hyperthyroidism at the end of a
                                                                                                           course of antithyroid drugs is contro-
                                                                                                           versial.
                                                                                                          J Clin Endocrinol Metab
                                                                                                           1989;69:1093.

Thyroxine, total,       Total T4 is a measure of thyroid gland Increased in: Hyperthyroidism,             Total T4 should be interpreted with the
 serum                   secretion of T4, bound and free, and   increased thyroid-binding globulin         TBG level or as part of a free thyrox-




                                                                                                                                                      Thyroxine, total
(T4)                     thus is influenced by serum thyroid     (TBG) (eg, pregnancy, drug). Drugs:        ine index.
                         hormone binding activity.              amiodarone, high-dose beta-blockers       Med Clin North Am 1991;75:1.
5.0–11.0 µg/dL                                                  (especially propranolol).                 Med Clin North Am 1991;75:27.
[64–142 nmol/L]                                                Decreased in: Hypothyroidism, low          Clin Chem 1996;42:146.
                                                                TBG due to illness or drugs, congenital
Marbled                                                         absence of TBG. Drugs: phenytoin,
$                                                               carbamazepine, androgens.




                                                                                                                                                                                                      169
                                                                                                                                                                                     170
Test /Range/Collection             Physiologic Basis                            Interpretation                                Comments
Thyroxine, free,         FT4 (if done by equilibrium dialysis or Increased in: Hyperthyroidism, non-            FT4 is functionally equivalent to the




                                                                                                                                                                                     Pocket Guide to Diagnostic Tests
 serum                    ultrafiltration method) is a more         thyroidal illness, especially psychiatric.    FT4I (see below).
(FT4)                     direct measure of the free T4 hor-       Drugs: amiodarone, beta-blockers             The free thyroxine and sensitive TSH
                          mone concentration (biologically         (high dose).                                  assays have similar sensitivities for
Varies with method        available hormone) than the free        Decreased in: Hypothyroidism, non-             detecting clinical hyperthyroidism




                                                                                                                                                             Thyroxine, free
                          T4 index.                                thyroidal illness. Drugs: phenytoin.          and hypothyroidism. The TSH assay
Marbled                  FT4 done by a two-step immunoassay                                                      detects subclinical dysfunction and
$$                        is similar to the free thyroxine index.                                                monitors thyroxine treatment better;
                         The presence of rheumatoid factor or                                                    the free thyroxine test detects central
                          drug treatment with furosemide, intra-                                                 hypothyroidism and monitors rapidly
                          venous heparin, and subcutaneous                                                       changing function better.
                          low-molecular-weight heparin may                                                      JAMA 1990;263:1529.
                          interfere with newer assays for free                                                  Arch Intern Med 1996;156:2333.
                          thyroxine.                                                                            Clin Chem 1996;42:146.
                                                                                                                Arch Intern Med 1998;158:266.
Thyroxine index, free, Free thyroxine index is expressed as    Increased in: Hyperthyroidism, non-              Test is useful in patients with clinically
 serum                  total T4 × T3 (or T4) resin uptake and thyroidal illness, especially psychiatric.        suspected hyper- or hypothyroidism,
(FT4I)                  provides an estimate of the level of    Drugs: amiodarone, beta-blockers                 in elderly patients admitted to geri-
                        free T4, since the T3 (or T4) resin     (high dose).                                     atric units, or in women over 40 with




                                                                                                                                                             Thyroxine index, free
6.5–12.5                uptake (ie, thyroid hormone binding Decreased in: Hypothyroidism, non-                   one or more somatic complaints.
                        ratio) is an indirect estimate of the   thyroidal illness. Drugs: phenytoin.            (See Thyroid function table, p 393.)
Marbled                 thyroid binding globulin (TBG) con-                                                     Screening for thyroid disease is not
$$                      centration. (TBG binds 70% of cir-                                                       indicated in younger women, men, or
                        culating thyroid hormone.)                                                               patients admitted with acute medical
                       The unbound form of circulating T4,                                                       or psychiatric illnesses because tran-
                        normally 0.03% of total serum T4,                                                        sient abnormalities are indistinguish-
                        determines the amount of T4 avail-                                                       able from true thyroid disease.
                        able to cells.                                                                          FT4I is functionally equivalent to the
                                                                                                                 FT4 (see above).
                                                                                                                Ann Intern Med 1990;112:840.
Toxoplasma antibody, Toxoplasma gondii is an obligate          Increased in: Acute or congenital toxo-   Single IgG titers of >1 256 are consid-
 serum or CSF           intracellular protozoan that causes     plasmosis (IgM), previous toxoplasma      ered diagnostic of active infection;
(Toxo)                  human infection via ingestion, trans- exposure (IgG), and false-positive          titers of >1 128 are suspicious. Titers
                        placental transfer, blood products, or (IgM) reactions (SLE, HIV infection,       of 1 16–1 64 may merely represent
IgG: <1 16              organ transplantation. Cats are the     rheumatoid arthritis).                    past exposure. If titers subsequently
IgM:                    definitive hosts of T gondii and pass                                              rise, they probably represent early
 Infant <1 2            oocysts in their feces. Human infec-                                              disease.
 Adult <1 8 titer       tion occurs through ingestion of                                                 IgM titer >1 16 is very important in




                                                                                                                                                                          Common Laboratory Tests: Selection and Interpretation
                        sporulated oocysts or via the                                                     the diagnosis of congenital toxo-
Marbled or CSF          transplacental route.                                                             plasmosis.
$$$                    In the immunodeficient host, acute                                                 High titer IgG antibody results should
Submit paired sera,     infection may progress to lethal                                                  prompt an IgM test. IgM, however, is




                                                                                                                                                    Toxoplasma antibody
 one collected within   meningoencephalitis, pneumonitis,                                                 generally not found in adult AIDS
 1 week of illness and  or myocarditis.                                                                   patients since the disease usually
 another 2–3 weeks     In acute primary infection, IgM anti-                                              represents a reactivation.
 later.                 bodies develop 1–2 weeks after onset                                             Some recommend ordering baseline
                        of illness, peak in 6–8 weeks, and                                                toxoplasma IgG titers in all asympto-
                        then decline. IgG antibodies develop                                              matic HIV-positive patients because a
                        on a similar time-course but persist                                              rising toxoplasma titer can help diag-
                        for years.                                                                        nose CNS toxoplasmosis in the
                       In adult infection, the disease usually                                            future.
                        represents a reactivation, not a pri-                                            Culture of the T gondii organism is
                        mary infection. Therefore, the IgM                                                difficult, and most laboratories are
                        test is less useful.                                                              not equipped for the procedure.
                       Approximately 30% of all US adults                                                (See also Brain abscess, p 197.)
                        have antibodies to T gondii.                                                     Ann Intern Med 1984;100:36.
                                                                                                         N Engl J Med 1988;318:271.
                                                                                                         Clin Infect Dis 1994;18:14.
                                                                                                         AIDS 1996;10:1521.
                                                                                                         J Clin Microbiol 1997;35:174.




                                                                                                                                                                          171
                                                                                                         J Clin Lab Anal 1997;11:214.
                                                                                                                                                                            172
Test /Range/Collection             Physiologic Basis                            Interpretation                                Comments
Triglycerides, serum     Dietary fat is hydrolyzed in the small Increased in: Hypothyroidism, diabetes          If serum is clear, the serum triglyceride
                                                                                                                  level is generally <350 mg/dL.




                                                                                                                                                                            Pocket Guide to Diagnostic Tests
(TG)                      intestine, absorbed and resynthesized mellitus, nephrotic syndrome, chronic
                          by mucosal cells, and secreted into       alcoholism (fatty liver), biliary tract     Despite extensive research, it remains
<165 mg/dL                lacteals as chylomicrons.                 obstruction, stress, familial lipoprotein     unclear whether triglycerides are an
[<1.65 g/L]              Triglycerides in the chylomicrons are      lipase deficiency, familial dysbetalipo-       independent risk factor for coronary
                          cleared from the blood by tissue          proteinemia, familial combined hyper-         artery disease.
Marbled                   lipoprotein lipase.                       lipidemia, obesity, viral hepatitis,        Triglycerides >1000 mg/dL can be
$                        Endogenous triglyceride production         cirrhosis, pancreatitis, chronic renal        seen when a primary lipid disorder is




                                                                                                                                                            Triglycerides
Fasting specimen          occurs in the liver. These triglycerides failure, gout, pregnancy, glycogen             exacerbated by alcohol or fat intake or
  required.               are transported in association with       storage diseases types I, III, and VI,        by corticosteroid or estrogen therapy.
                          β-lipoproteins in very low density        anorexia nervosa, dietary excess.           JAMA 1993;269:505.
                          lipoproteins (VLDL).                      Drugs: betablockers, cholestyramine,        Lancet 1993;342:781.
                                                                    corticosteroids, diazepam, diuretics,       N Engl J Med 1993;328:1220.
                                                                    estrogens, oral contraceptives.             Med Clin North Am 1994;78:117.
                                                                   Decreased in: Tangier disease                Circulation 1997;96:2520.
                                                                    (α-lipoprotein deficiency), hypo- and        Am J Cardiol 1998;81(4A):70B.
                                                                    abetalipoproteinemia, malnutrition,         Am J Cardiol 1998;82(12A):49U.
                                                                    malabsorption, parenchymal liver dis-       Am J Med 1998;105(1A):58S.
                                                                    ease, hyperthyroidism, intestinal lym-      Eur Heart J 1998;19(Suppl A):A36.
                                                                    phangiectasia. Drugs: ascorbic acid,
                                                                    clofibrate, nicotinic acid, gemfibrozil.
Triidothyronine, total, T3 reflects the metabolically active   Increased in: Hyperthyroidism (some),    T3 may be increased in approximately
 serum                   form of thyroid hormone and is influ- increased thyroid-binding globulin.       5% of hyperthyroid patients in whom




                                                                                                                                                  Triiodothyronine
(T3)                     enced by thyroid hormone-binding     Decreased in: Hypothyroidism, non-        T4 is normal (T3 toxicosis). Therefore,
                         activity.                             thyroidal illness, decreased thyroid-    test is indicated when hyperthyroidism
95–190 ng/dL                                                   binding globulin. Drugs: amiodarone.     is suspected and T4 value is normal.
[1.5–2.9 nmol/L]                                                                                       Test is of no value in the diagnosis of
                                                                                                        hypothyroidism.
Marbled                                                                                                Ann Intern Med 1990;112:840.




                                                                                                                                                                     Common Laboratory Tests: Selection and Interpretation
$$                                                                                                     JAMA 1990;263:1529.
                                                                                                       Am J Med 1994;96:229.




                                                                                                                                                                     173
                                                                                                                                                                            174
Test /Range/Collection             Physiologic Basis                          Interpretation                             Comments
Troponin-I, cardiac,     Troponin is the contractile regulatory Increased in: Myocardial infarction        Cardiac troponin I is a more specific




                                                                                                                                                                            Pocket Guide to Diagnostic Tests
 serum                    protein of striated muscle. It contains (sensitivity 50% at 4 hours, 97% at       marker for myocardial infarction than
(cTnI)                    three subunits: T, C, and I. Subunit I 6 hours; specificity 95%), cardiac          CKMB with roughly equivalent sen-
                          consists of three forms, which are       trauma, cardiac surgery, myocardial      sitivity early in the course of infarc-
< 1.5 ng/mL               found in slow-twitch skeletal muscle, damage following PTCA, defibrilla-           tion (4 –36 hours). Sensitivity and
                          fast-twitch skeletal muscle, and car-    tions, and other cardiac interventions,  specificity for peak concentrations of
Marbled                   diac muscle, respectively. Troponin I nonischemic dilated cardiomyopathy.         cTnI (100%; 96%) are equivalent to
$$                        is predominantly a structural protein Slight elevations noted in patients with or better than those for CK-MB
                          and is released into the circulation     recent aggravated unstable angina,       (88%; 93%) and total CK (73%;
                          after cellular necrosis. Cardiac tro-    muscular disorders, CNS disorders,       85%). cTnI appears in serum approxi-
                          ponin I is expressed only in cardiac     HIV infection, chronic renal failure,    mately 4 hours after onset of chest




                                                                                                                                                      Troponin-I, cardiac
                          muscle, throughout development and cirrhosis, sepsis, lung diseases, and          pain, peaks at 8–12 hours, and per-
                          despite pathology, and thus its pres-    endocrine disorders.                     sists for 5–7 days. This prolonged
                          ence in serum can distinguish           Not Increased in: Skeletal muscle dis-    persistence gives it much greater sen-
                          between myocardial injury and            ease (myopathy, myositis, dystrophy),    sitivity than CKMB for diagnosis of
                          skeletal muscle injury.                  noncardiac trauma or surgery, rhab-      myocardial infarction beyond the first
                         cTnI is measured by immunoassay           domyolysis, severe muscular exertion,    36– 48 hours. Minor elevations of car-
                          using monoclonal antibodies.             chronic renal failure.                   diac troponin I should be interpreted
                                                                                                            with caution, particularly in patients
                                                                                                            suffering from acute illnesses who do
                                                                                                            not have chest pain or prior myocar-
                                                                                                            dial infarction.
                                                                                                           Clin Chem 1994;40:1291.
                                                                                                           N Engl J Med 1994;330:670.
                                                                                                           Clin Chem 1995;41:1266.
                                                                                                           N Engl J Med 1997;337:1648.
                                                                                                           Am Heart J 1999;137:332.
                                                                                                           Am J Emerg Med 1999;17:225.
Tularemia agglu-        Francisella tularensis is an organism Increased in: Tularemia; cross-reaction Single titers of >1 160 are indicative
 tinins, serum           of wild rodents (rabbits and hares)     with brucella antigens and proteus OX- of infection. Maximum titers are
                         that infects humans (eg, trappers and 19 antigen (but at lower titers).         >1 1280.
<1 80 titer              skinners) via contact with animal tis-                                         A history of exposure to rabbits, ticks,
                         sues, by the bite of certain ticks and                                          dogs, cats, or skunks is suggestive




                                                                                                                                                   Tularemia agglutinins
Marbled                  flies, and by consumption of under-                                              of—but is not a requirement for—
$$                       cooked meat or contaminated water.                                              the diagnosis. Most common presen-
                        Agglutinating antibodies appear in                                               tation is a single area of painful lym-




                                                                                                                                                                           Common Laboratory Tests: Selection and Interpretation
                         10–14 days and peak in 5–10 weeks.                                              phadenopathy with low-grade fever.
                         A four-fold rise in titers is typically                                         Initial treatment should be empiric.
                         needed to prove acute infection.                                               Culture of the organism is difficult, re-
                         Titers decrease over years.                                                     quiring special media, and hazardous
                                                                                                         to laboratory personnel. Serologic
                                                                                                         tests are the mainstay of diagnosis.
                                                                                                        Medicine 1985;64:251.
                                                                                                        N Engl J Med 1993;329:936.
                                                                                                        Semin Respir Infect 1997;12:61.
Type and cross-match, A type and cross-match involves ABO                                                A type and screen is adequate prepara-
 serum and red cells     and Rh grouping (see pp 44 and 154,                                              tion for operative procedures unlikely
(Type and cross)         respectively), antibody screen (see                                              to require transfusion.




                                                                                                                                                   Type and cross-match
                         p 53), and cross-match. (Compare                                                Unnecessary type and cross-match
Red                      with Type and Screen, below.)                                                    orders reduce blood availability and
$$                     A major cross-match involves testing                                               add to costs.
Specimen label must      recipient serum against donor cells.                                            In addition, a preordering system
 be signed by the per-   It uses antihuman globulin to detect                                             should be in place, indicating the
 son drawing the         recipient’s antibodies on donor                                                  number of units of blood likely to be
 blood.                  red cells.                                                                       needed for each operative procedure.
A second “check”       If the recipient’s serum contains a                                               Technical Manual of the American
 specimen is needed at clinically significant alloantibody                                                 Association of Blood Banks, 11th ed.
 some hospitals.         by antibody screen, a cross-match                                                American Association of Blood




                                                                                                                                                                           175
                         is required.                                                                     Banks, 1993.
                                                                                                                                                                      176
Test /Range/Collection            Physiologic Basis                        Interpretation                              Comments
Type and screen,         Type and screen includes ABO and     A negative antibody screen implies that a Type and screen is indicated for patients




                                                                                                                                                                      Pocket Guide to Diagnostic Tests
 serum and red cells      Rh grouping (see pp 44 and 154,       recipient can receive un-cross-matched    undergoing operative procedures
                          respectively) and antibody screen     type-specific blood with minimal risk.     unlikely to require transfusion. How-
Red or lavender           (see p 53). (Compare with Type      If the recipient’s serum contains a clini-  ever, in the absence of preoperative
$$                        and Cross-Match, above.)              cally significant alloantibody by anti-    indications, routine preoperative blood
Specimen label must                                             body screen, a cross-match is required. type and screen testing is not cost-




                                                                                                                                                    Type and screen
 be signed by the per-                                                                                    effective and may be eliminated for
 son drawing the                                                                                          some procedures, such as laparoscopic
 blood.                                                                                                   cholecystectomy, expected vaginal
A second “check”                                                                                          delivery, and vaginal hysterectomy.
 specimen is needed at                                                                                   Technical Manual of the American
 some hospitals.                                                                                          Association of Blood Banks, 11th ed.
                                                                                                          American Association of Blood
                                                                                                          Banks, 1993.
                                                                                                         Am J Obstet Gynecol 1996;175:1201.
                                                                                                         Obstet Gynecol 1998;94(4 Part 1):493.
                                                                                                         Surg Endosc 1999;13:146.
Uric acid, serum   Uric acid is an end product of nucleo- Increased in Renal failure, gout, myelo-      Sex, age, and renal function affect uric
                    protein metabolism and is excreted     proliferative disorders (leukemia, lym-      acid levels.
Males: 2.4–7.4      by the kidney.                         phoma, myeloma, polycythemia vera),         The incidence of hyperuricemia is
Females 1.4–5.8    An increase in serum uric acid con-     psoriasis, glycogen storage disease          greater in some ethnic groups (eg,
 mg/dL              centration occurs with increased       (type I), Lesch-Nyhan syndrome               Filipinos) than others (whites).
[Males: 140–440     nucleoprotein synthesis or catabo-     (X-linked hypoxanthine-guanine phos-        Hyperuricemia may be a marker for
Females: 80–350     lism (blood dyscrasias, therapy of     phoribosyltransferase deficiency), lead       excess cardiovascular risk.
 µmol/L]            leukemia) or decreased renal uric      nephropathy, hypertensive diseases of       Clin Chem 1992;38:1350.




                                                                                                                                                               Common Laboratory Tests: Selection and Interpretation
                    acid excretion (eg, thiazide diuretic  pregnancy, menopause. Drugs: anti-          Postgrad Med J 1994;70:486.




                                                                                                                                                   Uric acid
Marbled             therapy or renal failure).             metabolite and chemotherapeutic             Metab Clin Experiment 1996;45:1557.
$                                                          agents, diuretics, ethanol, nicotinic       Am J Obstet Gynecol 1998;178:1067.
                                                           acid, salicylates (low dose),               Metab Clin Experiment 1998;47:435.
                                                           theophylline.                               J Hum Hypertens 1999;13:153.
                                                          Decreased in: SIADH, xanthine oxidase
                                                           deficiency, low-purine diet, Fanconi’s
                                                           syndrome, neoplastic disease (various,
                                                           causing increased renal excretion), liver
                                                           disease. Drugs: salicylates (high dose),
                                                           allopurinol (xanthine oxidase
                                                           inhibitor).




                                                                                                                                                               177
                                                                                                                                                                        178
Test /Range/Collection            Physiologic Basis                       Interpretation                            Comments
Vanillylmandelic        Catecholamines secreted in excess by Increased in: Pheochromocytoma    A 24-hour urine metanephrine test (p 125)




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
 acid, urine             pheochromocytomas are metabolized (96% sensitivity, 100% specificity), is the recommended test for the diagnosis




                                                                                                                                                Vanillylmandelic acid
(VMA)                    by the enzymes monoamine oxidase     neuroblastoma, ganglioneuroma,    of pheochromocytoma. (See also Pheo-
                         and catechol-O-methyltransferase to generalized anxiety.               chromocytoma algorithm, p 355.)
2–7 mg/24 h              VMA, which is excreted in urine.    Decreased in: Drugs: monoamine    A special diet is not needed when VMA
[10–35 µmol/d]                                                oxidase inhibitors.               test is done by the usual method.
                                                                                               <0.1% of hypertensive patients have a
Urine bottle containing                                                                         pheochromocytoma.
 hydrochloric acid                                                                             Am J Cardiol 1970;26:270.
$$                                                                                             Ann Surg 1974;179:740.
Collect 24-hour urine.                                                                         Neuropsychobiology 1995;31:6.
                                                                                               Psychiatr Res 1995;57:1.
Venereal Disease         This syphilis test measures nontrepo- Increased in: Syphilis: primary      VDRL is used as a syphilis screening test
 Research Labora-         nemal antibodies that are produced    (59–87%), secondary (100%), late     and in suspected cases of primary and
 tory test, serum         when Treponema pallidum interacts     latent (79–91%), tertiary (37–94%); secondary syphilis. Positive tests should




                                                                                                                                                VDRL test, serum
(VDRL)                    with host tissues. The VDRL usually collagen-vascular diseases (rheuma- be confirmed with an FTA-ABS or
                          becomes reactive at a titer of >1 32  toid arthritis, SLE), infections     MHA-TP test (see pp 92 and 129,
Nonreactive               within 1–3 weeks after the genital    (mononucleosis, leprosy, malaria),   respectively).
                          chancre appears.                      pregnancy, drug abuse.              The VDRL has similar sensitivity and
Marbled                                                                                              specificity to the RPR (see Syphilis test
$                                                                                                    table, p 391).
                                                                                                    Ann Intern Med 1986;104:368.
                                                                                                    Ann Intern Med 1991;114:1005.
                                                                                                    Sex Trans Dis 1998;26:12.
Venereal Disease         The CSF VDRL test measures nontre- Increased in: Tertiary neurosyphilis The quantitative VDRL is the test of
 Research Labora-         ponemal antibodies that develop in (10–27%).                            choice for CNS syphilis.
 tory test, CSF           the CSF when Treponema pallidum                                        Since the sensitivity of CSF VDRL is very
(VDRL)                    interacts with the central nervous                                      low, a negative test does not rule out
                          system.                                                                 neurosyphilis. Clinical features, CSF
Nonreactive                                                                                       white cell count, and CSF protein should
                                                                                                  be used together to make the diagnosis
$$                                                                                                (see CSF profiles, p 369).
                                                                                                 Because the specificity of the CSF VDRL




                                                                                                                                                               Common Laboratory Tests: Selection and Interpretation
Deliver in a clean plas-
 tic or glass tube.                                                                               test is high, a positive test confirms the
                                                                                                  presence of neurosyphilis.
                                                                                                 Patients being screened for neurosyphilis
                                                                                                  with CSF VDRL testing should have a
                                                                                                  positive serum RPR, VDRL, FTA-ABS,




                                                                                                                                              VDRL test, CSF
                                                                                                  MHA-TP test or other evidence of
                                                                                                  infection.
                                                                                                 Repeat testing may be indicated in HIV-
                                                                                                  infected patients in whom neurosyphilis
                                                                                                  is suspected.
                                                                                                 When the CSF VDRL is negative but sus-
                                                                                                  picion of CNS syphilis is high, other
                                                                                                  commonly used laboratory tests (CSF
                                                                                                  FTA-ABS, serum FTA-ABS, CSF Trepo-
                                                                                                  nema Pallidum hemagglutination [TPHA],
                                                                                                  serum TPHA, and CSF cells) can, in com-
                                                                                                  bination, identify 87% of patients with
                                                                                                  neurosyphilis with 94% specificity.
                                                                                                 Neurology 1985;35:1368.
                                                                                                 West J Med 1988;149:47.
                                                                                                 Neurology 1990;40:541.
                                                                                                 Am J Clin Pathol 1991;95:397.




                                                                                                                                                               179
                                                                                                 Gen Hosp Psychiatry 1995;17:305.
                                                                                                 Sex Trans Dis 1996;23:392.
                                                                                                                                                                     180
Test /Range/Collection              Physiologic Basis                           Interpretation                              Comments
Vitamin B12, serum      Vitamin B12 is a necessary cofactor       Increased in: Leukemia (acute myelo-         Differentiation among the causes of




                                                                                                                                                                     Pocket Guide to Diagnostic Tests
                         for three important biochemical           cytic, chronic myelocytic, chronic           vitamin B12 deficiency can be accom-
140–820 pg/mL            processes: conversion of methyl-          lymphocytic, monocytic), marked              plished by a vitamin B12 absorption
[100–600 pmol/L]         malonyl-CoA to succinyl-CoA               leukocytosis, polycythemia vera.             (Schilling’s) test (see below).
                         and methylation of homocysteine to        (Increased B12 levels are not diag-         The commonly available competitive
Marbled                  methionine and demethylation of           nostically useful.)                          protein binding assay measures total
$$                       methyltetrahydrofolate to tetrahydro- Decreased in: Pernicious anemia, gas-            B12. It is insensitive to significant
Serum vitamin B12        folate (THF). Consequent deficiency trectomy, gastric carcinoma, mal-                   decreases in physiologically signifi-
 specimens should be     of folate coenzymes derived from          absorption (sprue, celiac disease,           cant B12 bound to TC II.




                                                                                                                                                       Vitamin B12
 frozen if not analyzed THF is probably the crucial lesion         steatorrhea, regional enteritis, fistulas,   Specificity of the serum vitamin B12
 immediately.            caused by B12 deficiency.                  bowel resection, Diphyllobothrium            test (approximately 73%) has not
                        All vitamin B12 comes from ingestion latum [fish tapeworm] infestation,                  been systematically studied.
                         of foods of animal origin.                small bowel bacterial overgrowth),          Neuropsychiatric disorders caused by
                        Vitamin B12 in serum is protein-bound, pregnancy, dietary deficiency, HIV                low serum B12 level can occur in the
                         70% to transcobalamin I (TC I) and        infection (with or without malabsorp-        absence of anemia or macrocytosis.
                         30% to transcobalamin II (TC II).         tion), chronic high-flux hemodialysis,       Br J Haematol 1993;83:643.
                         The B12 bound to TC II is physiologi- Alzheimer’s disease, drugs (eg, ome-            Essays Biochem 1994;28:63.
                         cally active; that bound to TC I is not. prazole, metformin, carbamazepine).          JAMA 1994;272:1233.
                                                                                                               Ann Intern Med 1994;120:211.
                                                                                                               Ann Clin Lab Sci 1997;27:249.
                                                                                                               Nephron 1997;75:259.
                                                                                                               Am J Med 1998;104:422.
Vitamin B12 absorp-       Absorption of vitamin B12 is depen-      Decreased in: Ileal disease or resection, Previously administered diagnostic and
 tion test, 24-hour        dent on two factors: adequate intrin-    bacterial overgrowth, B12 deficiency         therapeutic radiopharmaceuticals may
 urine                     sic factor produced by the stomach       (because megaloblastosis of the intesti- interfere with performance of the
(Schilling’s test)         antrum and normal ileal absorption.      nal wall leads to decreased B12 absorp- Schilling test for prolonged periods
                           Lack of either can lead to B12           tion, pernicious anemia (< 2.5%             of time.
Excretion of >8% of        deficiency.                               excretion of administered dose), post- If the patient’s creatinine clearance is
 administered dose                                                  gastrectomy, chronic pancreatitis, cys-     <60 mL/min, a 48-hour urine should
                                                                    tic fibrosis, giardiasis, Crohn’s disease. be collected.




                                                                                                                                                                                       Common Laboratory Tests: Selection and Interpretation
$$$$                                                                                                          Pernicious anemia is suggested by an




                                                                                                                                                         Vitamin B12 absorption test
Stage I: 0.5–1.0 µCi of                                                                                         abnormal stage I test, followed by a
 52Co-B is given                                                                                                normal stage II test (ie, addition of
          12
 orally, followed by                                                                                            intrinsic factor leads to normal
 1.0 mg of unlabeled                                                                                            intestinal absorption and urinary
 B12 IM 2 hours later.                                                                                          excretion).
 A 24-hour urine is                                                                                           Ileal malabsorption gives abnormal
 collected.                                                                                                     results in stages I and II.
Stage II: After 5 days,                                                                                       Low intrinsic factor contributing to B12
 test is repeated with                                                                                          deficiency is common in AIDS.
 60 mg active hog                                                                                             Egg yolk-bound B12 should be used
 intrinsic factor added                                                                                         rather than crystalline B12 to avoid
 to the oral labeled                                                                                            false negative tests.
 B12.                                                                                                         CRC Crit Rev Clin Lab Sci
                                                                                                                1988;26:263.
                                                                                                              Am J Gastroenterol 1992;87:1781.
                                                                                                              Mayo Clin Proc 1994;69:144.
                                                                                                              J Nuclear Med 1995;36:1659.
                                                                                                              J Nuclear Med 1996;37:1995.




                                                                                                                                                                                       181
                                                                                                                                                                                182
Test /Range/Collection             Physiologic Basis                          Interpretation                              Comments
Vitamin D3,              The vitamin D system functions to       Increased in: Heavy milk drinkers (up      Measurement of 25(OH)D3 is the best




                                                                                                                                                                                Pocket Guide to Diagnostic Tests
 25-hydroxy, serum        maintain serum calcium levels.          to 64 ng/mL), vitamin D intoxication,      indicator of both vitamin D defi-
 or plasma                Vitamin D is a fat-soluble steroid      sun exposure.                              ciency and toxicity. It is indicated in
(25[OH]D3)                hormone. Two molecular forms           Decreased in: Dietary deficiency, mal-       hypocalcemic disorders associated
                          exist: D3 (cholecalciferol), synthe-    absorption (rickets, osteomalacia),        with increased PTH levels, in chil-
10–50 ng/mL               sized in the epidermis, and D2          biliary and portal cirrhosis, nephrotic    dren with rickets and in adults with
[25–125 nmol/L]           (ergocalciferol), derived from plant    syndrome, lack of sun exposure,            osteomalacia. In hypercalcemic dis-




                                                                                                                                                       Vitamin D3, 25-hydroxy
                          sources. To become active, both         osteoarthritis, age. Drugs: phenytoin,     orders, 25(OH)D3 is useful in disor-
Marbled or green          need to be further metabolized.         phenobarbital.                             ders associated with decreased PTH
$$$                       Two sequential hydroxylations                                                      levels, or possible vitamin D over-
                          occur: in the liver to 25(OH)D3 and                                                dose (hypervitaminosis D).
                          then, in the kidney, to 1,25[OH]2D3.                                              Vitamin D toxicity is manifested by
                         Plasma levels increase with sun                                                     hypercalcemia, hyperphosphatemia,
                          exposure.                                                                          soft tissue calcification and renal
                                                                                                             failure.
                                                                                                            Adv Intern Med 1982;27:45.
                                                                                                            Mayo Clin Proc 1985;60:851.
                                                                                                            Endocrinol Metab Clin North Am
                                                                                                             1989;18:765.
                                                                                                            Lancet 1995;346:207.
                                                                                                            Ann Intern Med 1996;125:353.
                                                                                                            Arthritis Rheum 1999;42:854.
Vitamin D3, 1,25-      1,25-Dihydroxy vitamin D3 is the       Increased in: Primary hyperparathy-       Test is rarely needed.
 dihydroxy, serum or    most potent form of vitamin D.         roidism, idiopathic hypercalciuria, sar- Measurement of 1,25(OH) 2D3 is only
                                                                                                         useful in distinguishing 1 α-hydroxy-




                                                                                                                                                 Vitamin D3, 1,25-dihydroxy
 plasma                The main actions of vitamin D are the coidosis, some lymphomas,
(1,25[OH]2D3)           acceleration of calcium and phos-      1,25(OH) 2D3-resistant rickets, normal    lase deficiency from 1,25(OH) 2D3-
                        phate absorption in the intestine and  growth (children), pregnancy, lactation, resistant rickets or in monitoring
20–76 pg/mL             stimulation of bone resorption.        vitamin D toxicity.                       vitamin D status of patients with
                                                              Decreased in: Chronic renal failure,       chronic renal failure.
Marbled or green                                               anephric patients, hypoparathyroidism, Test is not useful for assessment of
                                                               pseudohypoparathyroidism, 1 α-




                                                                                                                                                                              Common Laboratory Tests: Selection and Interpretation
$$$$                                                                                                     vitamin D intoxication, because of
                                                               hydroxylase deficiency, post-              efficient feedback regulation of
                                                               menopausal osteoporosis.                  1,25(OH) 2D3 synthesis.
                                                                                                        Adv Intern Med 1982;27:45.
                                                                                                        N Engl J Med 1989;320:980.
                                                                                                        Ann Intern Med 1995;122:511.




                                                                                                                                                                              183
                                                                                                                                                                                     184
Test /Range/Collection            Physiologic Basis                         Interpretation                             Comments
von Willebrand’s         von Willebrand’s factor (vWF) is pro- Increased in: Inflammatory states (acute In von Willebrand’s disease, the platelet




                                                                                                                                                                                     Pocket Guide to Diagnostic Tests
 factor protein           duced by endothelial cells, circulates phase reactant).                         count and morphology are generally
 (immunologic),           in the plasma complexed to factor      Decreased in: von Willebrand’s disease. normal and the bleeding time is usu-
 plasma                   VIII coagulant protein, and mediates                                            ally prolonged (markedly prolonged
(vWF)                     platelet adhesion. vWF is a marker                                              by aspirin). Variant forms associated




                                                                                                                                                   von Willebrand’s factor protein
                          of endothelial injury.                                                          with mild thrombocytopenia and
44–158% units            Both quantitative and qualitative                                                angiodysplasia are described. The PTT
                          changes can cause disease.                                                      may not be prolonged if factor VIII
Blue                     vWF can be measured as protein anti-                                             coagulant level is >30%. Diagnosis is
$$$                       gen (immunologic measure) or by                                                 suggested by bleeding symptoms and
                          ristocetin cofactor activity                                                    family history.
                          (functional assay).                                                            Laboratory diagnosis of von Wille-
                                                                                                          brand’s disease has become more dif-
                                                                                                          ficult because of the identification of
                                                                                                          numerous variant forms. In the classic
                                                                                                          type I disease, vWF antigen is
                                                                                                          decreased.
                                                                                                         Blood 1987;70:895.
                                                                                                         Mayo Clin Proc 1991;66:832.
                                                                                                         Thromb Haemost 1998;80:4095.
D-Xylose   absorption      Xylose is normally easily absorbed     Decreased in: Intestinal malabsorption, Test can be helpful in distinguishing
 test, urine                from the small intestine. Measuring    small intestinal bacterial overgrowth,    intestinal malabsorption (decreased
                            xylose in serum or its excretion in    renal insufficiency, small intestinal HIV D-xylose absorption) from pancreatic
>5 g per 5-hour urine       urine after ingestion evaluates the    enteropathy, cryptosporidiosis, cyto-     insufficiency (normal D-xylose
 (>20% excreted in          carbohydrate absorption ability of     toxic therapy-related malabsorption.      absorption).
 5 hours)                   the proximal small intestine.                                                   Urinary xylose excretion may be spuri-




                                                                                                                                                         D-Xylose
                                                                                                             ously decreased in renal failure, thus
$$$                                                                                                          limiting the specificity and usefulness




                                                                                                                                                                           Common Laboratory Tests: Selection and Interpretation
Fasting patient is given                                                                                     of the test. In this case, a serum xylose




                                                                                                                                                         absorption test
 D-xylose, 25 g in two                                                                                       level (gray top tube) obtained 1 hour
 glasses of water, fol-                                                                                      after administration of a 25-g dose of
 lowed by four glasses                                                                                       D-xylose can be used to evaluate
 of water over the next                                                                                      xylose absorption. The normal level
 2 hours. Urine is col-                                                                                      should be > 29 mg/dL (1.9 mmol/L).
 lected for 5 hours and                                                                                     Dig Dis Sci 1991;36:188.
 refrigerated.                                                                                              J Acquir Immune Defic Syndr
                                                                                                             1992;5:1047.
                                                                                                            Gastroenterology 1995;108:1075.
                                                                                                            Dig Dis Sci 1997;42:2599.
                                                                                                            J Clin Oncol 1997;15:2254.




                                                                                                                                                                           185
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                                                                            4
                 Therapeutic Drug Monitoring:
             Principles and Test Interpretation




                                                 Diana Nicoll, MD, PhD, MPA




        UNDERLYING ASSUMPTIONS

        The basic assumptions underlying therapeutic drug monitoring are that
        drug metabolism varies from patient to patient and that the plasma level
        of a drug is more closely related to the drug’s therapeutic effect or tox-
        icity than is the dosage.



        INDICATIONS FOR DRUG MONITORING

        Drugs with a narrow therapeutic index (where therapeutic drug levels
        do not differ greatly from levels associated with serious toxicity) should
        be monitored. Example: Lithium.
              Patients who have impaired clearance of a drug with a narrow ther-
        apeutic index are candidates for drug monitoring. The clearance mech-
        anism of the drug involved must be known. Example: Patients with
        renal failure have decreased clearance of gentamicin and therefore are
        at a higher risk for gentamicin toxicity.
                                           187
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
188   Pocket Guide to Diagnostic Tests

     Drugs whose toxicity is difficult to distinguish from a patient’s
underlying disease may require monitoring. Example: Theophylline in
patients with chronic obstructive pulmonary disease.
     Drugs whose efficacy is difficult to establish clinically may re-
quire monitoring of plasma levels. Example: Phenytoin.


SITUATIONS IN WHICH DRUG MONITORING
MAY NOT BE USEFUL

Drugs that can be given in extremely high doses before toxicity is
apparent are not candidates for monitoring. Example: Penicillin.
      If there are better means of assessing drug effects, drug level moni-
toring may not be appropriate. Example: Warfarin is monitored by pro-
thrombin time and INR (International Normalized Ratio) determinations,
not by serum levels.
      Drug level monitoring to assess compliance is limited by the in-
ability to distinguish noncompliance from rapid metabolism without
direct inpatient scrutiny of drug administration.
      Drug toxicity cannot be diagnosed with drug levels alone; it is a
clinical diagnosis. Drug levels within the usual therapeutic range do not
rule out drug toxicity in a given patient. Example: Digoxin, where other
physiologic variables (eg, hypokalemia) affect drug toxicity.
      In summary, therapeutic drug monitoring may be useful to guide
dosage adjustment of certain drugs in certain patients. Patient compli-
ance is essential if drug monitoring data are to be correctly interpreted.


OTHER INFORMATION REQUIRED FOR EFFECTIVE
DRUG MONITORING

Reliability of the Analytic Method
The analytic sensitivity of the drug monitoring method must be ade-
quate. For some drugs, plasma levels are in the nanogram per milliliter
range. Example: Tricyclic antidepressants, digoxin.
      The specificity of the method must be known, since the drug’s
metabolites or other drugs may interfere. Interference by metabolites—
which may or may not be pharmacologically active—is of particular con-
cern in immunologic assay methods using antibodies to the parent drug.
      The precision of the method must be known in order to assess
whether changes in levels are caused by method imprecision or by clin-
ical changes.
            Therapeutic Drug Monitoring: Principles and Test Interpretation   189

Reliability of the Therapeutic Range
Establishing the therapeutic range for a drug requires a reliable clinical
assessment of its therapeutic and toxic effects, together with plasma
drug level measurements by a particular analytic method. In practice,
as newer, more specific analytic methods are introduced, the therapeu-
tic ranges for those methods are estimated by comparing the old and
new methodologies—without clinical correlation.

Pharmacokinetic Parameters
Five pharmacokinetic parameters that are important in therapeutic drug
monitoring include:
      1. Bioavailability. The bioavailability of a drug depends in part on
its formulation. A drug that is significantly metabolized as it first passes
through the liver exhibits a marked “first-pass effect,” reducing the
effective oral absorption of the drug. A reduction in this first-pass effect
(eg, because of decreased hepatic blood flow in heart failure) could
cause a clinically significant increase in effective oral drug absorption.
      2. Volume of distribution and distribution phases. The volume
of distribution of a drug determines the plasma concentration reached
after a loading dose. The distribution phase is the time taken for a drug
to distribute from the plasma to the periphery. Drug levels drawn
before completion of a long distribution phase may not reflect levels
of pharmacologically active drug at sites of action. Examples: Digoxin,
lithium.
      3. Clearance. Clearance is either renal or nonrenal (usually
hepatic). Whereas changes in renal clearance can be predicted on the
basis of serum creatinine or creatinine clearance, there is no routine
liver function test for assessment of hepatic drug metabolism. For most
therapeutic drugs measured, clearance is independent of plasma drug
concentration, so that a change in dose is reflected in a similar change
in plasma level. If, however, clearance is dose-dependent, dosage
adjustments produce disproportionately large changes in plasma levels
and must be made cautiously. Example: Phenytoin.
      4. Half-life. The half-life of a drug depends on its volume of dis-
tribution and its clearance and determines the time taken to reach a
steady state level. In three or four half-lives, the drug level will be 87.5%
to 93.75% of the way to steady state. Patients with decreased drug clear-
ance and therefore increased drug half-lives will take longer to reach a
higher steady state level. In general, since non-steady state drug levels
are potentially misleading and can be difficult to interpret, it is recom-
mended that most clinical monitoring be done at steady state.
190   Pocket Guide to Diagnostic Tests

      5. Protein binding of drugs. All routine drug level analysis
involves assessment of both protein-bound and free drug. However,
pharmacologic activity depends on only the free drug level. Changes in
protein binding (eg, in uremia or hypoalbuminemia) may significantly
affect interpretation of reported levels for drugs that are highly protein-
bound. Example: Phenytoin. In such cases, where the ratio of free to
total measured drug level is increased, the usual therapeutic range based
on total drug level will not apply.

Drug Interactions
For patients receiving several medications, the possibility of drug inter-
actions affecting drug elimination must be considered. Example: Quini-
dine, verapamil, and amiodarone decrease digoxin clearance.

Time to Draw Levels
In general, the specimen should be drawn after steady state is reached
(at least 3 or 4 half-lives after a dosage adjustment) and just before the
next dose (trough level).
      Peak and trough levels may be indicated to evaluate the dosage of
drugs whose half-lives are much shorter than the dosing interval. Exam-
ple: Gentamicin.

Reference
Winter M: Basic Clinical Pharmacokinetics, 3rd ed. Applied Thera-
    peutics, 1994.
TABLE 4–1. THERAPEUTIC DRUG MONITORING.

     Drug            Effective Concentrations         Half-Life (hours)        Dosage Adjustment                                   Comments




                                                                                                                                                                             Therapeutic Drug Monitoring: Principles and Test Interpretation
Amikacin            Peak: 10–25 µg/mL                         2–3              ↓ in renal dysfunction   Concomitant kanamycin or tobramycin therapy may give falsely
                    Trough: <10 µg/mL                     ↑ in uremia                                    elevated amikacin results by immunoassay.
Amitriptyline       160–240 ng/mL                            9–46                                       Drug is highly protein-bound. Patient-specific decrease in protein
                                                                                                         binding may invalidate quoted range of effective concentration.
Carbamazepine       4–8 µg/mL                                10–30                                      Induces its own metabolism. Metabolite 10,11-epoxide exhibits
                                                                                                         13% cross-reactivity by immunoassay. Toxicity: diplopia,
                                                                                                         drowsiness, nausea, vomiting, and ataxia.
Cyclosporine        150–400 mg/mL(ng/L)                      6–12              Need to know             Cyclosporine is lipid-soluble (20% bound to leukocytes; 40% to
                     whole blood                                                specimen and             erythrocytes; 40% in plasma, highly bound to lipoproteins).
                                                                                methodology              Binding is temperature-dependent, so whole blood is preferred to
                                                                                used                     plasma or serum as specimen. High-performance liquid
                                                                                                         chromatography or monoclonal fluorescence polarization
                                                                                                         immunoassay measures cyclosporine reliably. Polyclonal fluo-
                                                                                                         rescence polarization immunoassays cross-react with metabo-
                                                                                                         lites, so the therapeutic range used with those assays is higher.
                                                                                                         Anticonvulsants and rifampin increase metabolism. Erythromycin,
                                                                                                         ketoconazole, and calcium channel blockers decrease metabo-
                                                                                                         lism.
Desipramine         100–250 ng/mL                            13–23                                      Drug is highly protein-bound. Patient-specific decrease in protein
                                                                                                         binding may invalidate quoted range of effective concentration.

↔ = unchanged; ↑ = increased;, ↓ = decreased; CHF = congestive heart failure




                                                                                                                                                                             191
TABLE 4–1 (CONTINUED).




                                                                                                                                                                                192
      Drug            Effective Concentrations         Half-Life (hours)        Dosage Adjustment                                    Comments




                                                                                                                                                                                Pocket Guide to Diagnostic Tests
Digoxin              0.8–2 ng/mL                               42               ↓ in renal dysfunc-      Bioavailability of digoxin tablets is 50–90%. Specimen must not
                                                       ↑ in uremia, CHF,           tion, CHF              be drawn within 6 hours of dose. Dialysis does not remove a sig-
                                                       hypothyroidism;                                    nificant amount. Hypokalemia potentiates toxicity. Digitalis toxic-
                                                       ↓ in hyper-                                        ity is a clinical and not a laboratory diagnosis. Digibind
                                                       thyroidism                                         (digoxin-specific antibody) therapy of digoxin overdose can inter-
                                                                                                          fere with measurement of digoxin levels depending on the digoxin
                                                                                                          assay. Elimination is reduced by quinidine, verapamil, and amio-
                                                                                                          darone.
Ethosuximide         40–100 mg/L                            Child: 30                                    Levels used primarily to assess compliance. Toxicity is rare and
                                                            Adult: 50                                     does not correlate well with plasma concentrations.
Gentamicin           Peak: 4–8 µg/mL                           2–5              ↓ in renal dysfunction   Draw peak specimen 30 minutes after end of infusion. Draw trough
                     Trough: <2 µg/mL                  ↑ in uremia                                        just before next dose. In uremic patients, carbenicillin may reduce
                                                       (7.3 on dialysis)                                  gentamicin half-life from 46 hours to 22 hours. If a once-daily
                                                                                                          regimen (5 mg/kg) is used to maximize bacterial killing by opti-
                                                                                                          mizing the peak concentration/MIC ratio and to reduce the poten-
                                                                                                          tial for toxicity, dosage should be reduced if trough concentration
                                                                                                          is >1 µg/mL (1 mg/L). Measurement of peak concentrations is
                                                                                                          not recommended with this regimen.
Imipramine           180–350 ng/mL                            10–16                                      Drug is highly protein-bound. Patient-specific decrease in protein
                                                                                                          binding may invalidate quoted range of effective concentration.
Lidocaine            1–5 µg/mL                                  1.8             ↓ in CHF, liver dis-     Levels increased with cimetidine therapy. CNS toxicity common in
                                                       ↔ in uremia, CHF;        ease                      the elderly.
                                                       ↑ in cirrhosis

 ↔ = unchanged; ↑ = increased;, ↓ = decreased; CHF = congestive heart failure
Lithium              0.7–1.5 meq/L                              22             ↓ in renal dysfunction   Thiazides and loop diuretics may increase serum lithium levels.
                                                           ↑ in uremia
Methotrexate                                                   8.4             ↓ in renal dysfunction   7-Hydroxymethotrexate cross-reacts 1.5% in immunoassay. To
                                                           ↑ in uremia                                   minimize toxicity, leucovorin should be continued if methotrexate
                                                                                                         level is > 0.1 µmol/L at 48 hours after start of therapy. Methotrex-




                                                                                                                                                                                Therapeutic Drug Monitoring: Principles and Test Interpretation
                                                                                                         ate >1µmol/L at >48 hours requires an increase in leucovorin
                                                                                                         rescue therapy.
Nortriptyline        50– 40 ng/mL                            18–44                                      Drug is highly protein-bound. Patient-specific decrease in protein
                                                                                                         binding may invalidate quoted range of effective concentration.
Phenobarbital        10–30 µg/mL                                86             ↓ in liver disease       Metabolized principally by the hepatic microsomal enzyme
                                                          ↑ in cirrhosis                                system. Many drug-drug interactions.
Phenytoin            10–20 µg/mL                        Dose-dependent                                  Metabolite cross-reacts 10% in immunoassay. Metabolism is
                     ↓ in uremia,                                                                       capacity-limited. Increase dose cautiously when level approaches
                      hypoalbuminemia                                                                   therapeutic range, since new steady state level may be dispropor-
                                                                                                        tionately higher. Drug is very highly protein-bound, and when
                                                                                                        protein-binding is decreased in uremia and hypoalbuminemia,
                                                                                                        the usual therapeutic range does not apply. In this situation, use
                                                                                                        a reference range of 5–10 µg/mL.
Primidone            5–10 µg/mL                                 8                                       Phenobarbital cross-reacts 0.5%. Metabolized to phenobarbital.
                                                                                                         Primidone/phenobarbital ratio >1 2 suggests poor compliance.
Procainamide         4–8 µg/mL                                  3              ↓ in renal dysfunction   Thirty percent of patients with plasma levels of 12–16 µg/mL have
                                                           ↑ in uremia                                   ECG changes; 40% of patients with plasma levels of 16 µg/mL
                                                                                                         have severe toxicity. Metabolite N-acetylprocainamide is active.

↔ = unchanged; ↑ = increased;, ↓ = decreased; CHF = congestive heart failure




                                                                                                                                                                                193
TABLE 4–1 (CONTINUED).




                                                                                                                                                                               194
      Drug            Effective Concentrations         Half-Life (hours)        Dosage Adjustment                                     Comments




                                                                                                                                                                               Pocket Guide to Diagnostic Tests
Quinidine            1–5 µg/L                                    7              ↓ in liver disease, CHF   Effective concentration is lower in chronic liver disease and
                                                        ↔ in CHF                                           nephrosis where binding is decreased.
                                                        ↑ in liver disease
Salicylate           150–300 µg/mL                       Dose-dependent                                   See Figure 8–23, p 360, for nomogram of salicylate toxicity.
                      (15–30 mg/dL)
Theophylline         5–20 µg/mL                                 9               ↓ in CHF, cirrhosis,      Caffeine cross-reacts 10%. Elimination is increased 1.5–2 times in
                                                                                and with cimetidine        smokers. 1,3-Dimethyl uric acid metabolite increased in uremia
                                                                                                           and because of cross-reactivity may cause an apparent slight
                                                                                                           increase in serum theophylline.
Tobramycin           Peak: 5–10 µg/mL                          2–3              ↓ in renal dysfunction    Tobramycin, kanamycin, and amikacin may cross-react in
                     Trough: <2 µg/mL                      ↑ in uremia                                     immunoassay. If a once-daily regimen is used to maximize bacter-
                                                                                                           ial killing by optimizing the peak concentration/MIC ratio and to
                                                                                                           reduce the potential for toxicity, dosage should be reduced if
                                                                                                           trough concentration is >1 µg/mL (1 mg/L). Measurement of
                                                                                                           peak concentrations is not recommended with this regimen.
Valproic acid        55–100 µg/mL                             13–19                                       Ninety-five percent protein-bound. Reduced binding in uremia and
                                                                                                           cirrhosis.
Vancomycin           Trough: 5–15 µg/mL                         6               ↓ in renal dysfunction    Toxicity in uremic patients leads to irreversible deafness. Keep
                                                           ↑ in uremia                                     peak level < 30– 40 µg/mL to avoid toxicity.

 ↔ = unchanged; ↑ = increased;, ↓ = decreased; CHF = congestive heart failure
                                                                            5
                       Microbiology: Test Selection




                                                             Mary K. York, PhD




        HOW TO USE THIS SECTION

        This section displays information about clinically important infec-
        tious diseases in tabular form. Included in these tables are the Organ-
        isms involved in the disease/syndrome listed; Specimens/Diagnostic
        Tests that are useful in the evaluation; and Comments regarding the
        tests and diagnoses discussed. Topics are listed by body area/organ
        system: Central Nervous System, Eye, Ear, Sinus, Upper Airway,
        Lung, Heart and Vessels, Abdomen, Genitourinary, Bone, Joint, Mus-
        cle, Skin, and Blood.

        Organisms
        This column lists organisms that are known to cause the stated illness.
        Scientific names are abbreviated according to common usage (eg,
        Streptococcus pneumoniae as S pneumoniae or pneumococcus). Spe-
        cific age or risk groups are listed in order of increasing age or frequency
        (eg, Infant, Child, Adult, HIV).
              When bacteria are listed, Gram stain characteristics follow the
        organism name in parentheses—eg, “S pneumoniae (GPDC).” The fol-
        lowing abbreviations are used:
                                           195
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
196   Pocket Guide to Diagnostic Tests

GPC Gram-positive cocci                  GNC Gram-negative cocci
GPDC Gram-positive diplococci            GNDC Gram-negative diplococci
GPCB Gram-positive coccobacilli          GNCB Gram-negative coccobacilli
GPR Gram-positive rods                   GNR Gram-negative rods
GVCB Gram-variable coccobacilli          AFB Acid-fast bacilli

     When known, the frequency of the specific organism’s involve-
ment in the disease process is also provided in parentheses—eg,
“S pneumoniae (GPDC) (50%).”

Specimen Collection/Diagnostic Tests
This column describes the collection of specimens, laboratory process-
ing, useful radiographic procedures, and other diagnostic tests. Culture
or test sensitivities with respect to the diagnosis in question are placed
in parentheses immediately following the test when known—eg, “Gram
stain (60%).” Pertinent serologic tests are also listed. Keep in mind that
few infections can be identified by definitive diagnostic tests and that
clinical judgment is critical to making difficult diagnoses when test
results are equivocal.

Comments
This column includes general information about the utility of the tests
and may include information about patient management. Appropriate
general references are also listed.

Syndrome Name/Body Area
In the last two columns the syndrome name and body area are placed
perpendicular to the rest of the table to allow for quick referencing.
          Organism                            Specimen /Diagnostic Tests                                         Comments
Brain Abscess                     Blood for bacterial cultures.                             Occurs in patients with otitis media and sinusitis.
                                  Brain abscess aspirate for Gram stain (82%), bacte-        Also seen in patients with cyanotic congenital heart
Usually polymicrobial              rial (88%), AFB, fungal cultures, and cytology.           disease and right-to-left shunting (eg, tetralogy of
Child: anaerobes (40%), S aureus Lumbar puncture is dangerous and contraindicated.           Fallot) or arteriovenous vascular abnormalities of
 (GPC), S pneumoniae (GPDC),      Sources of infection in the ears, sinuses, lungs or        the lung (eg, Osler-Weber-Rendu).
 S pyogenes (GPC in chains),       bloodstream should be sought for culture when            Majority of toxoplasmosis abscesses are multiple
 viridans streptococci (GPC in     abscess is found.                                         and are seen on MRI in the basal ganglia, parietal
 chains), less common, Entero-    CT scan and MRI are the most valuable imaging              and frontal lobes.




                                                                                                                                                                    CENTRAL NERVOUS SYSTEM
 bacteriaceae (GNR), P aeruginosa procedures and can guide biopsy if a specimen is          99mTechnetium brain scan is a very sensitive test for

 (GNR), H influenzae (GNCB),        needed. (See CT scan, MRI of head, p 245.)                abscess and the test of choice where CT and MRI
 N meningitidis (GNDC)            Serum toxoplasma antibody in HIV-infected patients         are unavailable.
Adults: Viridans and anaerobic     may not be positive at outset of presumptive ther-       J Child Neurol 1995;10:283.




                                                                                                                                                    Brain Abscess
 streptococci (GPC in chains)      apy. If negative or if no response to empiric ther-      Clin Infect Dis 1996;23:1061.
 (60–70%), bacteroides (GNR)       apy, biopsy may be needed to rule out lymphoma,          Clin Infect Dis 1997;25:763.
 (20– 40%), Enterobacteriaceae     fungal infection, or tuberculosis. Biopsy material       Neurol Clin 1998;16:419.
 (GNR) (23–33%), S aureus          should be sent for toxoplasma antigen (DFA).
 (GPC) (10–15%), other anaer-     Detection of toxoplasma DNA in blood or CSF sam-




                                                                                                                                                                                             Microbiology: Test Selection
 obes, including fusobacterium     ples by PCR techniques is now available from spe-
 (GNR) and actinomyces (GPR),      cialized or reference laboratories. A positive PCR
 T solium (cysticerci)             result must be interpreted in the context of the clin-
Immunocompromised : T gondii,      ical presentation. Active or recent infection is indi-
 C neoformans, nocardia (GPR),     cated by a positive IgM antibody test.
 mycobacteria (AFB), fungi,       (See also toxoplasma antibody, p 171.)
 E histolytica.
Posttraumatic: S aureus (GPC),
 Enterobacteriaceae (GNR),
 coagulase-negative staphylococci
 (GPC), P acnes (GPR)




                                                                                                                                                                                             197
                                                                                                                                                                                        198
           Organism                                 Specimen /Diagnostic Tests                                     Comments
Encephalitis                           CSF for pressure (elevated), cell count (WBCs ele-      CT scan with contrast or MRI with gadolinium
                                        vated but variable [10–2000/µL], mostly lympho-         showing temporal lobe lesions suggests herpes




                                                                                                                                                                                        Pocket Guide to Diagnostic Tests
Arboviruses (California group, St.      cytes), protein (elevated, especially IgG fraction),    simplex.
 Louis, western equine),                glucose (normal), RBCs (especially in herpes-          Polyradiculopathy is highly suggestive of CMV
 enteroviruses (coxsackie, echo,        virus). Repeat examination of CSF after 24 hours        in AIDS.
 polio), herpes simplex (HSV),          often useful. (See CSF profiles, p 369.)                Clin Neuropathol 1995;14:187.




                                                                                                                                                               CENTRAL NERVOUS SYSTEM
 B henselae, lymphocytic chorio-       CSF cultures for viruses and bacteria (low yield).      Ann Intern Med 1996;125:577.
 meningitis, mumps, tick-borne         CSF PCR in reference laboratories for CMV (33%),        Clin Infect Dis 1996;23:219.
 encephalitis virus, post-infectious    HSV (98%), VZV, and enterovirus.                       Postgrad Med 1998;103:123.
 (following influenza, human her-       Identification of HSV DNA in CSF by PCR tech-            Ann Intern Med 1998;128:922.




                                                                                                                                                Encephalitis
 pes virus 6 [HHV-6], measles,          niques is now the definitive diagnostic test.           J Neurosurg 1998;89:640.
 mumps, rubella, varicella-zoster      Throat swab for enterovirus, mumps.                     J Child Neurol 1999;14:1.
 [VZV]), rabies, Creutzfeldt-          Stool culture for enterovirus, which is frequently      J Clin Microbiol 1999;37:2127.
 Jakob                                  shed for weeks (especially in children).
Postvaccination: Rabies, pertussis.    Urine culture for mumps.
Immunocompromised:                     Culture of both skin biopsy from hairline and saliva
 Cytomegalovirus (CMV), toxo-           for rabies.
 plasmosis, papovavirus (PML)          Single serum for bartonella (cat-scratch disease)
                                        IgM and IgG.
                                       Paired sera for arboviruses, mumps, or rabies should
                                        be drawn acutely and after 1–3 weeks of illness.
                                        Serologic tests are often of academic interest only.
                                        Not indicated for herpes simplex.
Aseptic Meningitis               CSF for pressure (elevated), cell count (WBCs            Aseptic meningitis is acute meningeal irritation in
                                  10–100/µL, PMNs early, lymphocytes later),               the absence of pyogenic bacteria or fungi. Diagno-
Acute: Enteroviruses (coxsackie,  protein (normal or slightly elevated), and glucose       sis is usually made by the examination of the CSF




                                                                                                                                                                       CENTRAL NERVOUS SYSTEM
 echo, polio) (90%), mumps,       (normal). (See CSF profiles, p 369.)                      and by ruling out other infectious causes (eg,
 herpes simplex (HSV), HIV       CSF viral culture can be negative despite active viral    syphilis, tuberculosis). Consider nonsteroidal anti-
 (primary HIV seroconversion),    infection. Enteroviruses can be isolated from the        inflammatory drugs as a noninfectious cause.




                                                                                                                                                  Aseptic Meningitis
 varicella-zoster (VZV), lympho- CSF in the first few days after onset but only rarely     Enteroviral aseptic meningitis is rare after age 40.
 cytic choriomeningitis virus     after the first week.                                    Patients with deficiency of the complement regula-
 (rare).                         Detection of enteroviral RNA in CSF by PCR from           tory protein factor I may have recurrent aseptic
Recurrent: Herpes simplex type 2  specialized or reference laboratories.                   meningitis.
 (Mollaret’s syndrome)           Urine viral culture for mumps.                           J Clin Microbiol 1997;35:691.
                                 Vesicle direct fluorescent antibody (DFA) or culture      Clin Microbiol Rev 1998;11:202.
                                  for HSV or VZV.                                         Acta Neurol Scand 1998;98:209.
                                 Paired sera for viral titers: poliovirus, mumps, and
                                  VZV. Not practical for other organisms unless
                                  actual isolate known and then only useful
                                  epidemiologically.
                                 Detection of VZV or HSV in CSF by PCR.




                                                                                                                                                                                                Microbiology: Test Selection
                                                                                                                                                                                                199
                                                                                                                                                                                                    200
           Organism                             Specimen /Diagnostic Tests                                       Comments
Bacterial Meningitis                CSF for pressure (> 180 mm H2O), cell count            The first priority in the care of the patient with sus-
                                     (WBCs 1000–100,000/µL, > 50% PMNs), protein            pected acute meningitis is therapy, then diagnosis.




                                                                                                                                                                                                    Pocket Guide to Diagnostic Tests
Neonate: E coli (GNR), group B       (150–500 mg/dL), glucose (< 40% of serum).             Antibiotics should be started within 30 minutes of
 or D streptococci (GPC),            (See CSF profiles, p 369.)                              presentation. The death rate for meningitis is about
 L monocytogenes (GPR).             CSF for Gram stain of cytocentrifuged material          50% for pneumococcal, less for others.
Infant: Group B streptococci,        (positive in 70–80%).                                 With recurrent N meningitidis meningitis, suspect a




                                                                                                                                                                           CENTRAL NERVOUS SYSTEM
 S pneumoniae (GPC), N meningi- CSF culture for bacteria.                                   terminal complement component deficiency. With
 tidis (GNDC), Listeria mono-       Blood culture positive in 40–60% of patients with       other recurrent bacterial meningitides, suspect a
 cytogenes (GPR), H influenzae        pneumococcal, meningococcal, and H influenzae           CSF leak.




                                                                                                                                                    Bacterial Meningitis
 (GNCB).                             meningitis.                                           Postgrad Med 1998;103:102.
Child: S pneumoniae, N meningi- CSF antigen tests are no longer considered useful          Medicine (Baltimore) 1998;77:313.
 tidis, H influenzae.                 because of their low sensitivity and false-positive   Infect Dis Clin North Am 1999;13:711.
Adult: S pneumoniae, N meningi-      results.                                              Infect Dis Clin North Am 1999;13:579.
 tidis, L monocytogenes.
Postneurosurgical: S aureus
 (GPC), S pneumoniae, P acnes
 (GPR), coagulase-negative
 staphylococci (GPC),
 pseudomonas (GNR), E coli
 (GNR), other Enterobacteriaceae.
Alcoholic patients and the elderly:
 In addition to the adult organ-
 isms, Enterobacteriaceae,
 pseudomonas, H influenzae.
Fungal Meningitis                CSF for pressure (normal or elevated), cell count       The clinical presentation of fungal meningitis in
                                  (WBCs 50–1000/µL, mostly lymphocytes), protein          immunocompromised patients is that of an indolent
C neoformans (spherical, budding  (elevated), and glucose (decreased).                    chronic meningitis.
 yeast). C immitis (spherules),  Serum cryptococcal antigen (CrAg) for C neofor-         Prior to AIDS, cryptococcal meningitis was seen
 H capsulatum.                    mans (99%).                                             both in patients with cellular immunologic defi-
Immunocompromised: Aspergillus For other fungi, collect at least 5 mL of CSF for fun-     ciencies and in patients who lacked obvious defects




                                                                                                                                                                       CENTRAL NERVOUS SYSTEM
 sp, P boydii, candida sp.        gal culture. Initial cultures are positive in 40% of    (about 50% of cases).
                                  coccidioides cases and 27–65% of histoplasma           Cryptococcus is the most common cause of menin-
                                  cases. Repeat cultures are frequently needed.           gitis in AIDS patients and may present with normal




                                                                                                                                                   Fungal Meningitis
                                 Culture of bone marrow, skin lesions, or other in-       CSF findings.
                                  volved organs should also be performed if clini-       Titer of CSF CrAg can be used to monitor therapeu-
                                  cally indicated.                                        tic success (falling titer) or failure (unchanged or
                                 CSF India ink preparation for cryptococcus is not        rising titer) or to predict relapse during suppressive
                                  recommended because it is positive in only 50%          therapy (rising titer).
                                  of cases.                                              Clin Microbiol Rev 1995;8:515.
                                 Serum coccidioidal serology is a concentrated serum     Emerg Infect Dis 1996;2:109.
                                  immunodiffusion test for the organism (75–95%).        Clin Infect Dis 1996;22:240.
                                  CSF serologic testing is rarely necessary. (See coc-   Scand J Infect Dis 1998;30:485.




                                                                                                                                                                                                Microbiology: Test Selection
                                  cidioides serology, p 74.)
                                 Complement fixation test for histoplasma is avail-
                                  able from public health department laboratories
                                  (see p 109).
                                 Histoplasma antigen can be detected in urine, blood,
                                  or CSF in 61% of cases of histoplasma meningitis.




                                                                                                                                                                                                201
                                                                                                                                                                                                   202
           Organism                             Specimen /Diagnostic Tests                                        Comments
Spirochetal Meningitis/             Neuroborreliosis: CSF for pressure (normal or ele-     Neurosyphilis is a late stage of infection and can
 Neurologic diseases                 vated), cell count (WBCs elevated, mostly lympho-      present with meningovascular (hemiparesis,




                                                                                                                                                                                                   Pocket Guide to Diagnostic Tests
                                     cytes), protein (may be elevated), and glucose         seizures, aphasia), parenchymal (general paresis,
B burgdorferi (neuroborreliosis),    (normal).                                              tabes dorsalis), or asymptomatic (latent) disease.
 T pallidum (neurosyphilis),        Serum and CSF for serologic testing. False-positive    Because there is no single highly sensitive or spe-
 leptospira, other borreliae         serologic tests may occur. Western blots should be     cific test for neurosyphilis, the diagnosis must
                                     used to confirm borderline or positive results. CSF     depend on a combination of clinical and laboratory
                                     serology for anti-B burgdorferi IgM (90%). Culture     data. Therapy of suspected neurosyphilis should
                                     and PCR less specific.                                  not be withheld on the basis of a negative CSF




                                                                                                                                                                          CENTRAL NERVOUS SYSTEM
                                    For Lyme disease serologies, see p 122.                 VDRL if clinical suspicion is high.
                                    Acute syphilitic meningitis: CSF for pressure          In HIV neurosyphilis, treatment failures may be




                                                                                                                                                 Spirochetal Meningitis
                                     (elevated), cell count (WBCs 25–2000/µL, mostly        common.
                                     lymphocytes), protein (elevated), and glucose         Lyme disease can present as a lymphocytic meningi-
                                     (normal or low). (See CSF profiles, p 369.)             tis, facial palsy, or painful radiculitis.
                                    Serum VDRL. (See VDRL, serum, p 178.)                  Leptospirosis follows exposure to rats.
                                    CSF VDRL is the preferred test (see p 179), but is     Semin Neurol 1998;18:185.
                                     only 66% sensitive for acute syphilitic meningitis.   J Neurol Sci 1998;153:182.
                                    Neurosyphilis: CSF for pressure (normal), cell         Clin Infect Dis 1998;26:151.
                                     count (WBCs normal or slightly increased, mostly      J Clin Microbiol 1998;36:3138.
                                     lymphocytes), protein (normal or elevated),           J Emerg Med 1998;16:851.
                                     glucose (normal), and CSF VDRL.
                                    Serum VDRL, FTA-ABS, or MHA-TP should be
                                     done.
                                    Leptospirosis: CSF cell count (WBCs <500/µL,
                                     mostly monocytes), protein (slightly elevated), and
                                     glucose (normal).
                                    Urine for dark-field examination of sediment.
                                    Blood and CSF dark-field examination only positive
                                     in acute phase prior to meningitis.
                                    Serum for serology for IgM.
Parasitic Meningoencephalitis       CSF for pressure (normal or elevated), cell count     Naegleria follows exposure to warm fresh water.
                                     (WBCs 100–1000/µL, chiefly monocytes, lympho-         Ehrlichia follows exposure to horses and ticks.




                                                                                                                                                 Parasitic Meningoencephalitis
T gondii, E chaffeensis (human       cytes), protein (elevated), glucose (normal).        Pediatr Neurol 1996;15:230.
 monocytic ehrlichiosis) (HME)       Serology as for brain abscess.                       J Neuroophthalmol 1997;17:47.
 and other species of human gran- Ehrlichiosis: White blood cell count low                Infect Dis Clin North Am 1998;12:123.
 ulocytic ehrlichiosis (HGE),        (1300–4000/µL), platelets low (50,000–140,000/µL),
 E histolytica, N fowleri, T solium hepatic aminotransferases (tenfold above normal).
 (cysticerci).                       Buffy coat for Giemsa (1% in HME, 18–80% in
                                     HGE), PCR of blood available (50–90% depending




                                                                                                                                                                                 CENTRAL NERVOUS SYSTEM
                                     on prior therapy). Serum IgG and IgM usually not
                                     positive until the third week.
                                    Naegleria: CSF wet mount, culture, and Giemsa
                                     stain.
                                    Cysticercosis: Characteristic findings on CT and
                                     MRI are diagnostic. Serology is less sensitive.
Tuberculous Meningitis             CSF for pressure (elevated), cell count (WBCs          Tuberculous meningitis is usually secondary to rup-
                                    100–500/µL, PMNs early, lymphocytes later),            ture of a subependymal tubercle rather than blood-
M tuberculosis (MTb) (acid-fast     protein (elevated), glucose (decreased).               borne invasion.




                                                                                                                                                 Tuberculous Meningitis



                                                                                                                                                                                                          Microbiology: Test Selection
 bacilli [AFB])                     (See CSF profiles, p 369.)                             Since CSF stain and culture are not sensitive for
                                   CSF for AFB stain. Stain is positive in only 30%.       tuberculosis, diagnosis and treatment should be
                                    Cytocentrifugation and repeat smears increase          based on a combination of clinical and micro-
                                    yield.                                                 biologic data.
                                   CSF for AFB culture (positive in < 70%). Repeated      Evidence of inactive or active extrameningeal tuber-
                                    sampling of the CSF during the first week of ther-      culosis, especially pulmonary, is seen in 75% of
                                    apy is recommended; ideally, 3 or 4 specimens of       patients.
                                    5–10 mL each should be obtained (87% yield with       Radiol Clin North Am 1995;33:733.
                                    4 specimens). PCR available but not yet validated.    Surg Neurol 1995;44:378.
                                   DNA probes are available for rapid confirmation         Acta Neurol Belg 1995;95:80.
                                    from mycobacterial growth.




                                                                                                                                                                                                          203
                                                                                                                                                                        204
          Organism                            Specimen /Diagnostic Tests                                       Comments
Conjunctivitis                    Conjunctival Gram stain is especially useful if gono-   The causes of conjunctivitis change with the season.
                                   coccal infection is suspected.                          Adenovirus occurs mainly in the fall, H influenzae




                                                                                                                                                                        Pocket Guide to Diagnostic Tests
Neonate (ophthalmia neonato-      Bacterial culture for severe cases (routine bacterial    in the winter.
 rum): C trachomatis, N gonor-     culture) or suspected gonococcal infection.            Gonococcal conjunctivitis is an ophthalmologic
 rhoeae (GNDC), herpes            Conjunctival scrapings or smears by direct immuno-       emergency.
 simplex (HSV)                     fluorescent monoclonal antibody staining for            Cultures are usually unnecessary unless chlamydia
Children and adults: adenovirus,   C trachomatis.                                          or gonorrhea is suspected or the case is severe.
 staphylococci (GPC), herpes      Cell culture for chlamydia.                             Consider noninfectious causes (eg, allergy, contact




                                                                                                                                                 Conjunctivitis
 simplex (HSV), H influenzae       Detection of chlamydial DNA on ocular swabs by           lens deposits, trauma)
 (GNCB), S pneumoniae (GPDC), PCR techniques is available but not yet validated.          Clin Ther 1995:17:800.




                                                                                                                                                                  EYE
 S pyogenes (GPC), varicella-     Ocular HSV and VZV PCR available in reference           Clin Infect Dis 1995;21:479.
 zoster (VZV), N gonorrhoeae       laboratories.                                          Postgrad Med 1997;101:185.
 (GNDC), M lacunata (GNCB),                                                               Am Fam Physician 1998;57:735.
 bartonella sp (Parinaud’s oculo-
 glandular syndrome).
Adult inclusion conjunctivitis/
 trachoma: C trachomatis.
Acute hemorrhagic conjunctivitis
 (acute epidemic keratoconjunc-
 tivitis): enterovirus,
 coxsackievirus.
Keratitis                            Corneal scrapings for Gram stain, KOH, and culture.     Prompt ophthalmologic consultation is mandatory.
                                      Routine bacterial culture is used for most bacterial   Acanthamoeba infection occurs in soft contact
Bacteria: P aeruginosa (GNR),         causes, viral culture for herpes, and special media     (extended-wear) lens wearers and may resemble
 staphylococci (GPC), S pneumo-       for acanthamoeba (can be detected with trichrome        HSV infection on fluorescein examination
 niae (GPDC), moraxella sp.           or Giemsa stain of smears).                             (dendritic [“branching”] ulcer).
Virus: Herpes simplex (HSV)          Treatment depends on Gram stain appearance and          Bacterial keratitis is usually caused by contact lens
 (dendritic pattern on fluorescein     culture.                                                use or trauma. Fungal keratitis is usually caused




                                                                                                                                                     Keratitis
 slitlamp examination), varicella-   Corneal biopsy may be needed if initial cultures are     by trauma.
 zoster virus (VZV)                   negative.                                              Int Ophthalmol Clin 1998;38:115.
Contact lens: Acanthamoeba,                                                                  Int Ophthalmol Clin 1998;38:107.
 Enterobacteriaceae (GNR).                                                                   CLAO J 1998;24:52.
Fungus: Candida, fusarium,                                                                   Cornea 1998;17:3.
 aspergillus, rhodotorula, and                                                               Clin Microbiol Rev 1999;12:445.
 other filamentous fungi.                                                                     Cornea 1999;18:144.
Parasite: O volvulus (river blind-
 ness), microsporidia (HIV)




                                                                                                                                                                       EYE
Endophthalmitis                    Culture material from anterior chamber, vitreous    Endophthalmitis is an inflammatory process of the
                                    cavity, and wound abscess for bacteria, mycobacte- ocular cavity and adjacent structures. Rapid diag-
Spontaneous or postoperative:       ria, and fungi. Traumatic and postoperative cases   nosis is critical, since vision may be compromised.




                                                                                                                                                                             Microbiology: Test Selection
 S aureus (GPC), coagulase-         should have aqueous and vitreous aspiration for    Bacterial endophthalmitis usually occurs as a conse-
 negative staphylococci (GPC),      culture and smear (56%).                            quence of ocular surgery. Prophylactic antibiotic




                                                                                                                                                     Endophthalmitis
 S pneumoniae (GPDC), candida Conjunctival cultures are inadequate and misleading. use is of unproved benefit, though topical anti-
 sp; streptococci, non-group B                                                          biotics are widely used.
 (GPC in chains).                                                                      Also consider retinitis in immunocompromised
Trauma: Bacillus sp (GPR), fungi.                                                       patients, caused by CMV, HSV, VZV, and toxo-
Post-filtering bleb: Viridans group                                                      plasma (retinochoroiditis), which is diagnosed by
 streptococcus (57%), S pneumo-                                                         retinal examination.
 niae (GPDC), H influenzae                                                              Int Ophthalmol Clin 1996;36:163.
 (GNCB).                                                                               Ophthalmology 1996;103:757.
IV drug abuse: Add B cereus.                                                           Clin Infect Dis 1997;24:1172.
                                                                                       Curr Opin Ophthalmol 1998;9:66.




                                                                                                                                                                             205
                                                                                       Surv Ophthalmol 1998;43:193.
                                                                                                                                                                         206
           Organism                              Specimen /Diagnostic Tests                                     Comments
Otitis Media                        Tympanocentesis aspirate for Gram stain and bacterial Peak incidence of otitis media occurs in the first
                                     culture in the patient who has a toxic appearance.    3 years of life, especially between 6 and 24 months




                                                                                                                                                                         Pocket Guide to Diagnostic Tests
Infant, child, and adult: S pneumo- Otherwise, microbiologic studies of effusions are so   of age.
 niae (30%) (GPDC), H influenzae consistent that empiric treatment is acceptable.          In neonates, predisposing factors include cleft palate,
 (30%) (GNCB), M catarrhalis        CSF examination if clinically indicated.               hypotonia, mental retardation (Down’s syndrome).
 (10%) (GNDC), S aureus (GPC), Nasopharyngeal swab may be substituted for                 Tympanocentesis is indicated if the patient fails to
 S pyogenes (GPC in chains),         tympanocentesis.                                      improve after 48 hours or develops fever. It may
 M pneumoniae, C pneumoniae,        Blood culture in the toxic patient.                    hasten resolution and decrease sterile effusion.




                                                                                                                                                    Otitis Media
 “sterile.”                                                                               Persistent middle ear effusion may require place-




                                                                                                                                                                   EAR
Neonate: Same as above plus                                                                ment of ventilating or tympanostomy tubes.
 Enterobacteriaceae (GNR),                                                                Bullous myringitis suggests mycoplasma.
 group B streptococcus (GPC).                                                             Emerging antibiotic resistance should be considered
Endotracheal intubation: Pseudo-                                                           in choice of empiric antibiotic therapy.
 monas sp (GNR), klebsiella                                                               Int J Pediatr Otorhinolaryngol 1995;31:153.
 (GNR), Enterobacteriaceae                                                                Pediatr Clin North Am 1996;43:1165.
 (GNR).                                                                                   Pediatr Infect Dis J 1997;16:449.
Chronic: S aureus (GPC), P aerug-                                                         Pediatr Infect Dis J 1998;17:1105.
 inosa (GNR), anaerobes,                                                                  Pediatr Infect Dis J 1999;18:1.
 M tuberculosis (AFB).
Otitis Externa                      Ear drainage for Gram stain and bacterial culture,   Infection of the external auditory canal is similar to
                                     especially in malignant otitis externa.               infection of skin and soft tissue elsewhere.
Acute localized: S aureus (GPC),    CT or MRI can aid in diagnosis by demonstrating      If malignant otitis externa is present, exclusion of
 anaerobes (32%), S pyogenes         cortical bone erosion or meningeal enhancement.       associated osteomyelitis and surgical drainage may
 (GPC in chains).                                                                          be required.
“Swimmer’s ear”: Pseudomonas                                                             Clin Infect Dis 1992;15:955.




                                                                                                                                                  Otitis Externa
 sp (GNR), Enterobacteriaceae                                                            Otolaryngol Clin North Am 1996;29:761.
 (GNR), vibrio (GNR), fungi                                                              Nurse Pract 1998;23:125.




                                                                                                                                                                   EAR
 (rare).                                                                                 Aust Fam Physician 1999;28:217.
Chronic: Usually secondary to
 seborrhea or eczema.
Diabetes mellitus, AIDS (“malig-
 nant otitis externa”): P aerugi-
 nosa (GNR), aspergillus sp.
Furuncle of external canal:
 S aureus.




                                                                                                                                                                         Microbiology: Test Selection
                                                                                                                                                                         207
                                                                                                                                                                          208
               Organism                            Specimen /Diagnostic Tests                                     Comments
Sinusitis                                  Nasal aspirate for bacterial culture is not      Diagnosis and treatment of sinusitis is usually based
                                            usually helpful.                                 on clinical and radiologic features. Microbiologic




                                                                                                                                                                          Pocket Guide to Diagnostic Tests
Acute: S pneumoniae (GPC) (31%),           Maxillary sinus aspirate for bacterial culture    studies can be helpful in severe or atypical cases.
 H influenzae (GNCB) (21%),                  may be helpful in severe or atypical cases.     Sinus CT scan (or MRI) is better than plain x-ray for
 M catarrhalis (GNDC), S pyogenes                                                            diagnosing sinusitis, particularly if sphenoid sinusi-
 (2–5%) (GPC), anaerobes (2–5%),                                                             tis is suspected. However, sinus CT scans should
 viruses (adenovirus, influenza, para-                                                        be interpreted cautiously, since abnormalities are
 influenza), S aureus (GPC) (rare).                                                           also seen in patients with the common cold.
Chronic (child): Viridans and anaerobic                                                     Acute and chronic sinusitis occur frequently in
 streptococci (GPC in chains) (23%),                                                         HIV-infected patients, may be recurrent or refrac-
 S aureus (19%), S pneumoniae,                                                               tory, and may involve multiple sinuses (especially
 H influenzae, M catarrhalis, P aerugi-                                                       when the CD4 cell count is <200/µL).
 nosa (GNR) in cystic fibrosis.                                                              Acute sinusitis often results from bacterial super-
Chronic (adult): Coagulase-negative                                                          infection following viral upper respiratory
 staphylococci (GPC) (36%), S aureus




                                                                                                                                                      Sinusitis
                                                                                             infection.




                                                                                                                                                                  SINUS
 (GPC) (25%), viridans streptococci
                                                                                            Pediatr Clin North Am 1996;43:1297.
 (GPC in chains) (8%), corynebacteria
                                                                                            J Otolaryngol 1996;25:249.
 (GPR) (5%), anaerobes (6%), including
 bacteroides sp, prevotella sp (GNR),                                                       Acta Otorhinolaryngol Belg 1997;51:305.
 peptostreptococcus (GPC), fuso-                                                            CMAJ 1997;15;156(Suppl 6):S1.
 bacterium sp (GNR).                                                                        Clin Infect Dis 1997;25:267.
Hospitalized with nasogastric tube or                                                       Ann Otol Rhinol Laryngol 1998;107:942.
 nasotracheal intubation: Enterobacteri-
 aceae (GNR), pseudomonas sp (GNR).
Fungal: Zygomycetes (rhizopus),
 aspergillus, P boydii.
Immunocompromised: P aeruginosa
 (GNR), cytomegalovirus (CMV),
 aspergillus sp. and other filamentous
 fungi plus microsporidia, Cryptosporid-
 ium parvum, acanthamoeba in HIV-
 infected patients.
Pharyngitis                               Throat swab for culture. Place in sterile tube   Controversy exists over how to evaluate patients
                                           or transport medium. If N gonorrhoeae sus-       with sore throat. Some authors suggest culturing all
Exudative: S pyogenes (GPC) (15–30%), pected, use chocolate agar or Thayer-Martin           patients and then treating only those with positive
 viruses (rhinovirus, coronavirus, adeno- media. If C diphtheriae suspected, use Tins-      cultures.
 virus) (25%), group C streptococcus       dale or blood agar. Throat swabs are rou-       In patients with compatible histories, be sure to con-
 (GPC), Epstein-Barr virus (mononucle-     tinely cultured for group A streptococcus        sider pharyngeal abscess or epiglottitis, both of




                                                                                                                                                    Pharyngitis
 osis), N gonorrhoeae (GNDC),              only. If other organisms are suspected, this     which may be life-threatening.
 Arcanobacterium hemolyticum (GPR).        must be stated.                                 Complications include pharyngeal abscess and
Membranous: C diphtheriae (GPR), C        Throat culture is about 70% sensitive for         Lemierre’s syndrome (infection with fuso-
 pseudodiphtheriticum (GPR),               group A streptococcus.                           bacterium sp.), which can progress to sepsis
 Epstein-Barr virus.                      “Rapid” tests for group A streptococcus can       and multi-organ failure.




                                                                                                                                                                  UPPER AIRWAY
                                           speed diagnosis and aid in the treatment of     Clin Infect Dis 1995;20:1512.
                                           family members. However, false-negative         Nurse Pract 1996;21:38.
                                           results may lead to underdiagnosis and fail-    Clin Infect Dis 1997;25:574.
                                           ure to treat.                                   J Clin Microbiol 1998;36:3468.
                                                                                           Int J Pediatr Otorhinolaryngol 1998;45:51.
Laryngitis                               Diagnosis is made by clinical picture of upper Laryngitis usually occurs with common cold or
                                          respiratory infection with hoarseness.         influenzal syndromes.




                                                                                                                                                                                 Microbiology: Test Selection
Virus (90%) (influenza, rhinovirus,                                                      Fungal laryngeal infections occur most commonly in
 adenovirus, parainfluenza, Epstein-Barr                                                  immunocompromised patients (AIDS, cancer,




                                                                                                                                                    Laryngitis
 virus), S pyogenes (GPC) (10%),                                                         organ transplants, corticosteroid therapy,
 M catarrhalis (GNDC) (55% of adults),                                                   diabetes mellitus).
 M tuberculosis, fungus (cryptococcosis,                                                Consider acid reflux for chronic cases.
 histoplasmosis).                                                                       Ann Otol Rhinol Laryngol 1993;102:209.
Immunocompromised: Candida sp,                                                          J Infect Dis 1996;174:636.
 cytomegalovirus, herpes simplex (HSV)                                                  Head Neck 1996;18:455.
                                                                                        J Voice 1998;12:91.




                                                                                                                                                                                 209
                                                                                                                                                                                               210
          Organism                               Specimen /Diagnostic Tests                                         Comments
Laryngotracheobronchitis            Nasopharyngeal aspirate for respiratory virus direct     Chronic bronchitis is diagnosed when sputum is
                                     fluorescent antigen (DFA), for viral culture (rarely      coughed up on most days for at least 3 consecutive




                                                                                                                                                                                               Pocket Guide to Diagnostic Tests
Infant/child: Respiratory syncytial indicated), and for PCR for B pertussis. PCR for          months for more than 2 successive years.
 virus (RSV) (50–75%) (bronchi-      pertussis is test of choice; culture and DFA are less   Bacterial infections are usually secondary infections
 olitis), adenovirus, parainfluenza sensitive. Cellular examination of early morning           of initial viral or mycoplasma-induced inflammation.
 virus (croup), B pertussis          sputum will show many PMNs in chronic                   Airway endoscopy can aid in the diagnosis of
 (GNCB) (whooping cough),            bronchitis.                                              bacterial tracheitis in children.
 other viruses, including rhino-    Sputum Gram stain and culture for ill adults. In         J Infect 1997;35:189.




                                                                                                                                                     Laryngotracheobronchitis
 virus, coronavirus, influenza.       chronic bronchitis, mixed flora are usually seen         Wien Klin Wochenschr 1997;109:574.




                                                                                                                                                                                UPPER AIRWAY
Adolescent/adult: Usually viruses, with oral flora or colonized H influenzae or                J Clin Microbiol 1997;35:2435.
 M pneumoniae, C pneumoniae,         S pneumoniae on culture.                                Nurse Pract 1997;22:104.
 B pertussis.                       Paired sera for viral, mycoplasmal, and chlamydial       Infect Dis Clin North Am 1998;12:671.
Chronic adult: S pneumoniae          titers can help make a diagnosis retrospectively in     Monaldi Arch Chest Dis 1999;54:43.
 (GPDC), H influenzae (GNCB),         infants and children but are not clinically useful      Can Respir J 1999;6:40A.
 M catarrhalis (GNDC), kleb-         except for seriously ill patients.
 siella (GNR), other Entero-
 bacteriaceae (GNR), viruses (eg,
 influenza), aspergillus (allergic
 bronchopulmonary aspergillosis).
Chronic obstructive airway disease:
 Viral (25–50%), S pneumoniae
 (GPC), H influenzae (GNCB),
 S aureus (GPC), Enterobacteri-
 aceae (GNR), anaerobes (<10%).
Epiglottitis                Blood for bacterial culture: positive in 50–100% of   Acute epiglottitis is a rapidly moving cellulitis of the
                             children with H influenzae.                            epiglottis and represents an airway emergency.
Child: H influenzae type B   Lateral neck x-ray may show an enlarged epiglottis    Epiglottitis can be confused with croup, a viral
 (GNCB).                     but has a low sensitivity (31%).                      infection of gradual onset that affects infants and




                                                                                                                                                            UPPER AIRWAY
Adult: S pyogenes (GPC),                                                           causes inspiratory and expiratory stridor. Airway




                                                                                                                                             Epiglottitis
 H influenzae.                                                                      management is the primary concern, and an endo-
HIV: Candida                                                                       tracheal tube should be placed or tracheostomy
                                                                                   performed as soon as the diagnosis of epiglottitis is
                                                                                   made in children. A tracheostomy set should be at
                                                                                   the bedside for adults.
                                                                                  Am J Emerg Med 1996;14:421.
                                                                                  Mayo Clin Proc 1998;73:1102.
                                                                                  J Otolaryngol 1998;27:332.
                                                                                  Pediatr Infect Dis J 1999;18:490.




                                                                                                                                                                           Microbiology: Test Selection
                                                                                                                                                                           211
                                                                                                                                                                                                212
             Organism                                        Specimen /Diagnostic Tests                                      Comments
Community-Acquired Pneumonia                      Sputum for Gram stain desirable; culture, if empi-        About 60% of cases of community-acquired
                                                   ric therapy fails or patient is seriously ill. An ade-    pneumonia have an identifiable microbial




                                                                                                                                                                                                Pocket Guide to Diagnostic Tests
Neonate: E coli (GNR), group A or B strepto-       quate specimen should have <10 epithelial cells           cause. Pneumatoceles suggest S aureus but
 coccus (GPC), S aureus (GPC), pseudo-             and > 25 PMNs per low-power field. Special spu-            are also reported with pneumococcus,
 monas sp (GNR), C trachomatis.                    tum cultures for legionella are available. DFA for        group A streptococcus, H influenzae, and
Infant/child (<5 years): Virus, S pneumoniae       legionella sp has a sensitivity of 25–70% and a           Enterobacteriaceae (in neonates).
 (GPC), H influenzae (GNCB), S aureus.              specificity of 95%. (Positive predictive value is         An “atypical pneumonia” presentation (dif-
Age 5–40 years: Virus, M pneumoniae, C pneu-       low in areas of low disease prevalence.)                  fuse pattern on chest x-ray with lack of
 moniae (formerly known as TWAR strain),          Blood for bacterial cultures, especially in ill            organisms on Gram stain of sputum)




                                                                                                                                                          Community-Acquired Pneumonia
 C psittaci, S pneumoniae, legionella sp.          patients.                                                 should raise suspicion of mycoplasma,
Age > 40 without other disease: S pneumoniae      Pleural fluid for bacterial culture if significant           legionella, or chlamydial infection. Con-
 (GPDC), H influenzae (GNCB), S aureus              effusion is present.                                      sider hantavirus pulmonary syndrome if
 (GPC), M catarrhalis (GNDC), C pneumoniae,       Bronchoalveolar lavage or brushings for bacte-             pulmonary symptoms follow afebrile
 legionella sp (GNR), C pseudodiphtheriticum       rial, fungal, and viral antigen tests and AFB             illness.
 (GPR), S pyogenes (GPC), K pneumoniae             culture in immunocompromised patients and                Aspirations are most commonly associated




                                                                                                                                                                                         LUNG
 (GNR), Enterobacteriaceae (GNR), N menin-         atypical cases.                                           with stroke, alcoholism, drug abuse, seda-
 gitidis (GNDC), viruses (eg, influenza)           Paired sera for M pneumoniae complement                    tion, and periodontal disease.
Cystic fibrosis: P aeruginosa (GNR), Burk-          fixation testing can diagnose infection                   Am Rev Resp Dis 1993;148:1418.
 holderia cepacia.                                 retrospectively.                                         Clin Infect Dis 1998;27:566.
Elderly: S pneumoniae (GPDC), H influenzae         Serologic tests for C pneumoniae, C psittaci              Clin Infect Dis 1998;26:811.
 (GNCB), S aureus (GPC), Enterobacteri-            strains, and Q fever are available. Serologic            Lancet 1998;352:1295.
 aceae (GNR), M catarrhalis (GNDC), group          tests and PCR for hantavirus (IgM and IgG)               Infect Dis Clin North Am 1998;12:689.
 B streptococcus (GPC), legionella (GNR),          are available.                                           Can Respir J 1999;6(Suppl A):15.
 nocardia (GPR), influenza.                        Other special techniques (bronchoscopy with tele-
Aspiration: S pneumoniae (GPDC), K pneu-           scoping plugged catheter on protected brush,
 moniae (GNR), Enterobacteriaceae (GNR),           transtracheal aspiration, transthoracic fine-needle
 bacteroides sp and other oral anaerobes.          aspiration, or, rarely, open lung biopsy) can be
Fungal: H capsulatum, C immitis, B dermatitidis    used to obtain specimens for culture in severe
Exposure to birthing animals, sheep: C burnetii    cases, in immunocompromised patients, or in
 (Q fever), rabbits: F tularensis (tularemia),     cases with negative conventional cultures and
 deer mice: hantavirus, birds: C psittaci.         progression despite empiric antibiotic therapy.
Anaerobic Pneumonia/Lung Abscess             Sputum Gram stain and culture for anaerobes are     Aspiration is the most important back-
                                              of little value because of contaminating oral       ground feature of lung abscess.




                                                                                                                                                Anaerobic Pneumonia
Usually polymicrobial: bacteroides sp (15%    flora.                                              Without clear-cut risk factors such as alco-
 B fragilis), peptostreptococcus, micro-     Bronchoalveolar sampling (brush or aspirate) for     holism, coma, or seizures, bronchoscopy is
 aerophilic streptococcus, veillonella,       Gram stain will usually make an accurate diag-      often performed to rule out neoplasm.
 S aureus, P aeruginosa, type 3 S pneumoniae nosis. As contamination is likely with a broncho-   Am J Ment Retard 1995;99:579.
 (rare), klebsiella (rare).                   scope alone, a Bartlett tube should be used.       J Periodontol 1996;67:1114.
                                             Percutaneous transthoracic needle aspiration may    Curr Opin Pulm Med 1997;3:120.
                                              be useful for culture and for cytology to demon-
                                              strate coexistence of an underlying carcinoma.
                                             Blood cultures are usually negative.
                                             Sputum Gram stain and culture for bacteria




                                                                                                                                                                              LUNG
Hospital-Acquired Pneumonia                                                                  Most cases are related to aspiration. Hospital-
                                              (aerobic and anaerobic) and fungus              acquired aspiration pneumonia is associated




                                                                                                                                                Hospital-Acquired Pneumonia
P aeruginosa (GNR), klebsiella (GNR),         (if suspected).                                 with intubation and the use of broad-
 S aureus (GPC), acinetobacter (GNR),        Blood cultures for bacteria are often negative.  spectrum antibiotics.
 Enterobacteriaceae (GNR), S pneumoniae      Endotracheal aspirate or bronchoalveolar sample A strong association between aspiration
 (GPDC), H influenzae (GNCB), influenza         for bacterial and fungal culture in selected    pneumonia and swallowing dysfunction is
 virus, respiratory syncytial virus (RSV),    patients.                                       demonstrable by videofluoroscopy.




                                                                                                                                                                                     Microbiology: Test Selection
 legionella (GNR), oral anaerobes.                                                           Mendelson’s syndrome is due to acute aspi-
Mendelson’s syndrome (see comments): No                                                       ration of gastric contents (eg, during anes-
 organisms initially, then pseudomonas,                                                       thesia or drowning).
 Enterobacteriaceae, S aureus, S pneumoniae.                                                 Infect Dis Clin North Am 1997;11:427.
                                                                                             Infect Dis Clin North Am 1998;12:761.
                                                                                             Am J Med 1998;105:319.
                                                                                             Chest 1999;115:28S.




                                                                                                                                                                                     213
                                                                                                                                                                                                  214
         Organism                                   Specimen /Diagnostic Tests                                      Comments
Pneumonia in the Immuno-               Expectorated sputum for Gram stain and bacterial       In PCP, the sensitivities of the various diagnostic
 compromised Host                       culture, if purulent.                                  tests are: sputum induction 80% (in experienced




                                                                                                                                                                                                  Pocket Guide to Diagnostic Tests
                                       Sputum induction or bronchiolar lavage for Giemsa       labs), bronchoscopy with lavage 90–97%, trans-
Child with HIV infection: Lym-          or methenamine silver staining or direct fluorescent    bronchial biopsy 94–97%.
 phoid interstitial pneumonia (LIP).    antibody (DFA) for P carinii trophozoites or cysts;   In PCP, chest x-ray may show interstitial (36%) or
AIDS: M avium (31%), P carinii          for mycobacterial, fungal staining and culture, for    alveolar (25%) infiltrates or may be normal (39%),
 (13%), cytomegalovirus (CMV)           legionella culture, and for CMV culture.               particularly if leukopenia is present.
 (11%), H capsulatum (7%),             Blood for CMV antigenemia or PCR from transplant       Recurrent episodes of bacterial pneumonia are




                                                                                                                                                     Pneumonia in Immunocompromised Host
 S pneumoniae (GPDC), H influen-         patients.                                              common.
 zae (GNCB), P aeruginosa              Blood or bone marrow fungal culture for histoplas-     Kaposi’s sarcoma of the lung is a common neo-
 (GNR), Enterobacteriaceae              mosis (positive in 50%), coccidioidomycosis            plastic process that can imitate infection in homo-
 (GNR), C neoformans, C pseudo-         (positive in 30%).                                     sexual and African HIV-infected patients.
 diphtheriticum (GPR), M tuber-        Blood culture for bacteria. Blood cultures are more    J Antimicrob Chemother 1995;36(Suppl B):59.
 culosis (AFB), C immitis,              frequently positive in HIV-infected patients with     Semin Respir Infect 1996;11:119.




                                                                                                                                                                                           LUNG
 P marneffei, Rhodococcus               bacterial pneumonia and often are the only source     Infect Dis Clin North Am 1998;12:781.
 equi (GPR).                            where a specific organism is identified; bacteremic     J Thorac Imaging 1998;13:247.
Neutropenic: Pseudomonas sp             patients have higher mortality rates.                 Haematologica 1999;84:71.
 (GNR), klebsiella, enterobacter       Histoplasma polysaccharide antigen positive in 90%     Clin Infect Dis 1999;28:341.
 (GNR), bacteroides sp and other        of AIDS patients with disseminated histoplasmosis;
 oral anaerobes, legionella, can-       antigen increases ≥ 2 RIA units with relapse.
 dida, aspergillus, mucor.             Immunodiffusion or CIE is useful for screening for,
Transplant recipients: Cytomegalo-      and CF for confirmation of, suspected histoplasmo-
 virus (CMV) (60–70%), P aerug-         sis or coccidioidomycosis.
 inosa (GNR), S aureus (GPC),          Serum cryptococcal antigen when pulmonary cryp-
 S pneumoniae (GPDC),                   tococcosis is suspected.
 legionella (GNR), respiratory         Serum lactate dehydrogenase (LDH) levels are
 syncytial virus (RSV), influenza        elevated in 63% and hypoxemia with exercise
 virus, P carinii, aspergillus,         (PaO2 < 75 mm Hg) occurs in 57% of PCP cases.
 P boydii, nocardia sp,
 strongyloides.
Mycobacterial Pneumonia           Sputum for AFB stain and culture. First morning          AFB found on sputum stain do not necessarily make
                                   samples are best, and at least three samples are         the diagnosis of tuberculosis, because M kansasii
M tuberculosis (MTb), M kansasii, required. Culture systems detect mycobacterial            and M avium-intracellulare look identical.
 M avium-intracellulare complex    growth in as little as several days to 6 weeks.         Tuberculosis is very common in HIV-infected
 (AFB, acid-fast beaded rods).    Bronchoalveolar lavage for AFB stain and culture or       patients, in whom the chest x-ray appearance may
                                   gastric washings for AFB culture can be used if          be atypical and occasionally (4%) may mimic PCP




                                                                                                                                                  Mycobacterial Pneumonia
                                   sputum tests are negative.                               (especially in patients with CD4 cell counts
                                  Sputum or bronchoalveolar lavage for PCR to MTb           < 200/µL). In one study, only 2% of patients sent
                                   available for confirmation of smear positive (99%),       for sputum induction for PCP had tuberculosis.




                                                                                                                                                                            LUNG
                                   less sensitive for smear negative (75%).                Consider HIV testing if MTb is diagnosed.
                                  CT- or ultrasound-guided transthoracic fine-needle        Delayed diagnosis of pulmonary tuberculosis is
                                   aspiration cytology can be used if clinical or radio-    common (up to 20% of cases), especially among
                                   graphic features are nonspecific or if malignancy is      patients who are older or who do not have respira-
                                   suspected.                                               tory symptoms.
                                                                                           In any patient with suspected tuberculosis, respira-
                                                                                            tory isolation is required.
                                                                                           Chest 1998;114:317.
                                                                                           Respiration 1998;65:163.




                                                                                                                                                                                   Microbiology: Test Selection
                                                                                           CMAJ 1999;160:1725.
                                                                                           Chest Surg Clin North Am 1999;9:227.




                                                                                                                                                                                   215
                                                                                                                                                                 216
           Organism                            Specimen /Diagnostic Tests                                      Comments
Empyema                            Pleural fluid for cell count (WBCs                      Chest tube drainage is paramount.
                                    25,000–100,000/µL, mostly PMNs), protein (> 50%       The clinical presentation of empyema is nonspecific.




                                                                                                                                                                 Pocket Guide to Diagnostic Tests
Neonate: E coli (GNR), group A      of serum), glucose (< serum, often very low), pH      Chest CT with contrast is helpful in demonstrating
 or B streptococcus (GPC),          (<7.20), LDH (> 60% of serum). (See Pleural fluid       pleural fluid accumulations due to mediastinal or
 S aureus (GPC), pseudomonas        profiles, p 382.)                                       subdiaphragmatic processes and can identify locu-
 sp (GNR).                         Blood cultures for bacteria.                            lated effusions, bronchopleural fistulae, and lung
Infant/child (< 5 years): S aureus Sputum for Gram stain and bacterial culture. Special    abscesses.
 (GPC), S pneumoniae (GPC),         culture can also be performed for legionella when     About 25% of cases result from trauma or surgery.
 H influenzae (GNCB), anaerobes. suspected.                                                Bronchoscopy is indicated when the infection is




                                                                                                                                                Empyema
Child (> 5 years)/adult, Acute:    Pleural fluid for Gram stain and bacterial culture       unexplained. Occasionally, multiple thoracenteses




                                                                                                                                                          LUNG
 S pneumoniae (GPC), group A        (aerobic and anaerobic).                               may be needed to diagnose empyema.
 streptococcus (GPC), S aureus                                                            Curr Opin Pulm Med 1998;4:185.
 (GPC), H influenzae (GNCB),                                                               Clin Chest Med 1998;19:363.
 legionella.                                                                              Semin Respir Infect 1999;14:18.
Child (> 5 years)/adult, chronic:                                                         Semin Respir Infect 1999;14:82.
 Anaerobic streptococci, bac-
 teroides sp, prevotella sp, por-
 phyromonas sp, fusobacterium
 sp, Enterobacteriaceae, E coli,
 Klebsiella pneumoniae,
 M tuberculosis.
Pericarditis                       In acute pericarditis, specific bacterial diagnosis is   Viral pericarditis is usually diagnosed clinically
                                    made in only 19%.                                       (precordial pain, muffled heart sounds, pericardial
Viruses: Enteroviruses (coxsackie, Pericardial fluid aspirate for Gram stain and bacte-      friction rub, cardiomegaly). The diagnosis is rarely
 echo), influenza, Epstein-Barr,     rial culture (aerobic and anaerobic). In acute peri-    aided by microbiologic tests.
 herpes zoster, mumps, HIV,         carditis, only 54% have pericardial effusions.         CT and MRI may demonstrate pericardial thickening.




                                                                                                                                                    Pericarditis
 CMV.                              Blood for buffy coat, stool or throat for enteroviral   Bacterial pericarditis is usually secondary to
Bacteria: S aureus (GPC), S pneu- culture. PCR available in reference laboratories.         surgery, immunosuppression (including HIV),
 moniae (GPC), mycoplasma,         Surgical pericardial drainage with biopsy of peri-       esophageal rupture, endocarditis with ruptured ring
 S pyogenes (GPC), Enterobacte-     cardium for culture (22%) and histologic                abscess, extension from lung abscess, aspiration
 riaceae (GNR), N meningitidis      examination.                                            pneumonia or empyema, or sepsis with pericarditis.




                                                                                                                                                                               HEART AND VESSELS
 (GNDC).                           Paired sera for enterovirus (coxsackie) and             Ann Thorac Surg 1997;63:1200.
Fungi: Candida                      mycoplasma.                                            Emerg Med Clin North Am 1998;16:665.
 (immunocompromised)                                                                       Am Heart J 1999;137:516.
                                                                                           Clin Cardiol 1999;22:334.
Tuberculous Pericarditis         PPD skin testing should be performed (negative in a       Spread from nearby caseous mediastinal lymph
                                  sizable minority).                                        nodes or pleurisy is the most common route of
Mycobacterium tuberculosis (MTb, Pericardial fluid obtained by needle aspiration can         infection. Acutely, serofibrinous pericardial effu-




                                                                                                                                                    Tuberculous Pericarditis
 AFB, acid-fast beaded rods)      show AFB by smear (rare) or culture (low yield).          sion develops with substernal pain, fever, and




                                                                                                                                                                                                   Microbiology: Test Selection
                                 The yield is improved by obtaining three or four           friction rub. Tamponade may occur.
                                  repeated specimens for smear and culture.                Tuberculosis accounts for 4% of cases of acute peri-
                                 Pericardial biopsy for culture and histologic exami-       carditis, 7% of cases of cardiac tamponade, and 6%
                                  nation has highest diagnostic yield.                      of cases of constrictive pericarditis.
                                 Other sources of culture for MTb besides peri-            One-third to one-half of patients develop constric-
                                  cardium are available in 50% of patients.                 tive pericarditis despite drug therapy. Constrictive
                                 Pericardial fluid may show markedly elevated levels         pericarditis occurs 2– 4 years after acute infection.
                                  of adenosine deaminase.                                  JAMA 1991;266:91.
                                                                                           Intern Med 1993;32:675.
                                                                                           Am Heart J 1993;126:249.
                                                                                           J Infect 1997;35:215.




                                                                                                                                                                                                   217
                                                                                                                                                                                                 218
           Organism                              Specimen /Diagnostic Tests                                      Comments
Infectious Myocarditis               Endomyocardial biopsy for pathologic examination,      Acute infectious myocarditis should be suspected in a
                                      PCR, and culture in selected cases. Indium-111         patient with dynamically evolving changes in ECG,




                                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
Enteroviruses (especially cox-        antimyosin antibody imaging is more sensitive than     echocardiography, and serum CK levels and symp-
 sackie B), adenovirus, influenza      endomyocardial biopsy.                                 toms of an infection. The value of endomyocardial
 virus, HIV, Borrelia burgdorferi Stool or throat swab for enterovirus culture. Blood        biopsy in such cases has not been established.




                                                                                                                                                                             HEART AND VESSELS
                                                                                                                                                    Infectious Myocarditis
 (Lyme disease), scrub typhus,        for enterovirus PCR (reference labs) and culture of   In contrast, an endomyocardial biopsy is needed to
 Rickettsia rickettsii (Rocky         white cells.                                           diagnose lymphocytic or giant cell myocarditis.
 Mountain spotted fever), Coxiella Paired sera for coxsackie B, Mycoplasma pneumo-          The incidence of myocarditis in AIDS may be as
 burnetii (Q fever), Mycoplasma       niae, Chlamydia pneumoniae, scrub typhus, Rick-        high as 46%.
 pneumoniae, Chlamydia pneumo- ettsia rickettsii, Coxiella burnetii, trichinella,           Many patients with acute myocarditis progress to
 niae, C diphtheriae (GPR),           toxoplasma.                                            dilated cardiomyopathy.
 Trichinella spiralis (trichinosis), Single serum for HIV, Borrelia burgdorferi,            Adv Pediatr 1997;44:141.
 Trypanosoma cruzi (Chagas’ dis- Trypanosoma cruzi.                                         J Infect 1998;37:99.
 ease), toxoplasma.                  Gallium scanning is sensitive but not specific for      J Am Coll Cardiol 1998;32:1371.
                                      myocardial inflammation.                               Emerg Med Clin North Am 1998;16:665.
                                     Antimyosin antibody scintigraphy has a high speci-     Adv Intern Med 1999;44:293.
                                      ficity but a lower sensitivity for the detection of    Circulation 1999;99:2011.
                                      myocarditis.
Infective Endocarditis            Blood cultures for bacteria. Three blood cultures are   Patients with congenital or valvular heart disease
                                   sufficient in 97% of cases. Blood cultures are fre-      should receive prophylaxis before dental proce-
Viridans group streptococci        quently positive with gram-positive organisms but       dures or surgery of the upper respiratory,
 (GPC), enterococcus (GPC),        can be negative with gram-negative or anaerobic         genitourinary, or gastrointestinal tract.
 nutritionally deficient strepto-   organisms.                                             In left-sided endocarditis, patients should be




                                                                                                                                                                        HEART AND VESSELS
 coccus (GPC), S aureus (GPC), If the patient is not acutely ill, therapy can begin        watched carefully for development of valvular




                                                                                                                                               Infective Endocarditis
 S pneumoniae (GPC),               after cultures identify an organism.                    regurgitation or ring abscess.
 Erysipelothrix rhusiopathiae     Transesophageal echocardiography (TEE) can help         The size and mobility of valvular vegetations on
 (GPR), brucella (GNR), Coxiella in diagnosis by demonstrating the presence of             TEE can help to predict the risk of arterial
 burnetii, C pneumoniae.           valvular vegetations (sensitivity > 90%), prosthetic    embolization.
Slow-growing fastidious GNRs:      valve dysfunction, valvular regurgitation, secondary   Clin Infect Dis 1997;25:1448.
 H parainfluenzae, H aphrophilus, “jet” or “kissing” lesions, and paravalvular abscess.    Infect Dis Clin North Am 1999;13:833.
 actinobacillus, cardiobacterium, SPECT immunoscintigraphy with antigranulocyte           Clin Infect Dis 1999;29:1.
 capnocytophaga, eikenella,        antibody can be used in cases of suspected infec-      Clin Infect Dis 1999;46:275.
 kingella (HACEK).                 tive endocarditis if echocardiography is non-          J Infection 1999;39:27.
                                   diagnostic.                                            Am J Med 1999;107:198.
                                                                                          J Infection 1999;38:87.
                                                                                          Postgrad Med J 1999;75:540.




                                                                                                                                                                                            Microbiology: Test Selection
                                                                                          Clin Infect Dis 1999;28:106.




                                                                                                                                                                                            219
                                                                                                                                                                                                                 220
            Organism                          Specimen /Diagnostic Tests                                        Comments
Prosthetic Valve Infective Endo- Blood cultures for bacteria and yeast. Three sets of     In a large series using perioperative prophylaxis, the
 carditis (PVE)                    blood cultures are sufficient in 97% of cases. Draw      incidences of early-onset and late-onset prosthetic




                                                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
                                   before temperature spike.                               valve endocarditis were 0.78% and 1.1%,




                                                                                                                                                   Prosthetic Valve Infective Endocarditis
Early (< 2 months): Coagulase-    While more invasive, transesophageal echo-               respectively.
 negative staphylococci (usually   cardiography is superior in predicting which           The portals of entry of early-onset PVE are intra-




                                                                                                                                                                                             HEART AND VESSELS
 S epidermidis with 80%            patients with infective endocarditis have perivalvu-    operative contamination and postoperative wound
 methicillin-resistant) (GPC)      lar abscess or prosthetic valve dysfunction and         infections. The portals of entry of late-onset PVE
 (27%), S aureus (GPC) (20%),      which are most susceptible to systemic embolism.        appear to be the same as those of native valve
 Enterobacteriaceae (GNR),                                                                 endocarditis, and the microbiologic profiles are
 diphtheroids (GPR), candida                                                               also similar.
 (yeast).                                                                                 Clinically, patients with late-onset PVE resemble
Late (> 2 months): Viridans group                                                          those with native valve disease. However, those
 streptococci (GPC) (42%),                                                                 with early-onset infection are often critically ill,
 coagulase-negative staphylococci                                                          more often have other complicating problems, are
 (21%), S aureus (11%), entero-                                                            more likely to go into shock and are more likely to
 coccus (GPC), Entero-                                                                     have conduction abnormalities due to ring abscess.
 bacteriaceae.                                                                            Medicine (Baltimore) 1997;76:94.
                                                                                          Clin Infect Dis 1997;24:884.
                                                                                          J Infect 1999;39:27.
Infectious Thrombophlebitis        Blood cultures for bacteria (positive in 80–90%).       Thrombophlebitis is an inflammation of the vein
                                   Catheter tip for bacterial culture to document etiol-    wall. Infectious thrombophlebitis is associated with
Associated with venous catheters:   ogy. More than 15 colonies (CFUs) suggests              microbial invasion of the vessel and is associated
 S aureus (GPC) (65–78%),           colonization or infection.                              with bacteremia and thrombosis.
 coagulase-negative staphylococci CT and MRI are the studies of choice in the evalua-      Risk of infection from an indwelling peripheral
 (GPC), candida sp (yeast),         tion of puerperal septic pelvic thrombophlebitis.       venous catheter goes up significantly after 4 days.




                                                                                                                                                   Infectious Thrombophlebitis
 pseudomonas sp (GNR), Entero-                                                             Arch Surg 1996;131:95.




                                                                                                                                                                                 HEART AND VESSELS
 bacteriaceae (GNR).                                                                       AJR Am J Roentgenol 1997;169:1039.
Hyperalimentation with catheter:                                                           Pediatr Infect Dis J 1997;16:63.
 Candida sp, Malassezia furfur                                                             World J Surg 1999;23:589.
 (yeast).                                                                                  Support Care Cancer 1999;7:386.
Indwelling venous catheter (eg,                                                            Infection 1999;27(Suppl 1):S11.
 Broviac, Hickman, Gershorn):
 S aureus, coagulase-negative
 staphylococci, diphtheroids
 (GPR), pseudomonas sp, Entero-
 bacteriaceae, candida sp.
Postpartum or post-abortion pelvic




                                                                                                                                                                                                     Microbiology: Test Selection
 thrombophlebitis: Bacteroides
 (GNR), Enterobacteriaceae, clos-
 tridium (GPR), streptococcus
 (GPC).




                                                                                                                                                                                                     221
                                                                                                                                                                                    222
            Organism                           Specimen /Diagnostic Tests                                      Comments
Gastritis                          Serum for antibody test (76–90% sensitivity but low     Also associated with duodenal ulcer, gastric carci-
                                    specificity) (see p 100).                                noma, and gastroesophageal reflux disease.




                                                                                                                                                                                    Pocket Guide to Diagnostic Tests
Helicobacter pylori                Stool for antigen detection test and [13C]urea breath   Clin Microbiol Rev 1997;10:720.




                                                                                                                                                 Gastritis
                                    test (99%) are specific noninvasive tests.              Aliment Pharmacol Ther 1998;12 (Suppl 1):61.]
                                   Gastric mucosal biopsy for rapid urea test (89%),       J Clin Microbiol 1999;37:3328.
                                    culture (89%), histology (92%), and PCR (99%)          J Gastroenterol 1999;34(Suppl 11):67.
                                    (reference laboratories).                              J Clin Microbiol 2000;38:13.




                                                                                                                                                                          ABDOMEN
                                                                                           Am J Gastroenterol 2000;95:72.
Infectious Esophagitis             Barium esophagram reveals abnormalities in the      Thrush and odynophagia in an immunocompromised




                                                                                                                                                 Infectious Esophagitis
                                    majority of cases of candidal esophagitis.          patient warrants empiric therapy for candida.
Candida sp (yeast), herpes simplex Endoscopy with biopsy and brushings for culture and Factors predisposing to infectious esophagitis include
 (HSV), cytomegalovirus (CMV), cytology has the highest diagnostic yield (57%) and HIV infection, exposure to radiation, cytotoxic
 varicella-zoster (VZV), Heli-      should be performed if clinically indicated or if   chemotherapy, recent antibiotic therapy,
 cobacter pylori (GNR),             empiric antifungal therapy is unsuccessful.         corticosteroid therapy, and neutropenia.
 cryptosporidium.                                                                      Gastrointest Endosc 1996;44:587.
(Rare causes: Mycobacterium                                                            Med Pediatr Oncol 1997;28:299.
 tuberculosis [AFB], aspergillus,                                                      Am J Gastroenterol 1998;93:394, 2239.
 histoplasma, blastomyces, HIV).                                                       Am J Gastroenterol 1999;94:339.
Infectious Colitis/Dysentery            Stool for occult blood helpful to diagnosis of E coli   Acute dysentery is diarrhea with bloody, mucoid
                                         O157:H7, salmonella, E histolytica.                     stools, tenesmus, and pain on defecation and
Infant: E coli (enteropathogenic).      Stool collected culture, ova and parasites examina-      implies an inflammatory invasion of the colonic
Child/Adult without travel, afebrile,    tion. Two samples are often needed. The sensitivity     mucosa. BUN and serum electrolytes may be indi-
 no gross blood or WBCs in stool:        of the stool culture is only 72%, but its specificity    cated for supportive care. Severe dehydration is a
 Rotavirus, caliciviruses (eg, Nor-      is 100% (using PCR as standard). One repeat cul-        medical emergency.
 walk agent), E coli (GNR).              ture may increase sensitivity. Special culture tech-   Necrotizing enterocolitis is a fulminant disease of
Child/Adult with fever, bloody           nique is needed for yersinia, E coli, and vibrio.       premature newborns; cause is unknown but human
 stool or history of travel to           Cultures for salmonella or shigella are not helpful     breast milk is protective. Air in the intestinal wall




                                                                                                                                                         Infectious Colitis/Dysentery
 subtropics/tropics (varies with         in patients hospitalized more than 72 hours.            (pneumatosis intestinalis), in the portal venous sys-
 epidemiology): Campylobacter           Proctosigmoidoscopy is indicated in patients with        tem, or in the peritoneal cavity seen on plain x-ray
 jejuni (GNR), E coli (GNR),             chronic or recurrent diarrhea or in diarrhea of         can confirm diagnosis. 30–50% of these infants




                                                                                                                                                                                        ABDOMEN
 (enterotoxigenic, enteroinvasive,       unknown cause for smears of aspirates (may show         will have bacteremia or peritonitis.
 enterohemorrhagic O157:H7),             organisms) and biopsy. Cultures of biopsy speci-       Risk factors for infectious colitis include poor
 shigella (GNR), salmonella              mens have somewhat higher sensitivities than stool      hygiene and immune compromise (infancy,
 (GNR), Yersinia enterocolitica          cultures.                                               advanced age, corticosteroid or immuno-
 (GNR), Clostridium difficile            Rectal and jejunal biopsies may be necessary in          suppressive therapy, HIV infection).
 (GPR), aeromonas (GNR), vibrio          HIV-infected patients. Need modified acid-fast          J Infect 1996 Nov;33:143.




                                                                                                                                                                                                  Microbiology: Test Selection
 (GNR), cryptosporidium, Ent-            stain for cryptosporidium.                             Arch Virol Suppl 1997;13:153.
 amoeba histolytica, Giardia lam-       Immunodiagnosis of G lamblia, cryptosporidium, or       J Infect Dis. 1997 Dec;176 (Suppl 2):S103.
 blia, cyclospora, strongyloides,        E histolytica cysts in stool is highly sensitive and   Am Fam Physician 1998;58:1769.
 edwardsiella (GNR).                     specific.                                               J Diarrhoeal Dis Res. 1998;16:248.
Child/Adult with vomiting and no                                                                Adv Pediatr 1999;46:353.
 fever: S aureus (GPC), Bacillus                                                                Emerg Infect Dis 1999;5:607.
 cereus (GPR).                                                                                  Annu Rev Med 1999;50:355.
                                                                                                Clin Lab Med 1999;19:553, 691.
                                                                                                Clin Infect Dis 1999;29:356.




                                                                                                                                                                                                  223
                                                                                                                                                                                                   224
           Organism                              Specimen /Diagnostic Tests                                          Comments
Antibiotic-Associated               Send stool for C difficile, cytotoxin A by tissue culture   Antibiotics cause changes in normal intestinal flora,
 Pseudomembranous Colitis            or toxin A or A and B by less sensitive immuno-            allowing overgrowth of C difficile and elaboration




                                                                                                                                                                                                   Pocket Guide to Diagnostic Tests
                                     assay. Testing two stools on different days will           of toxin.
Clostridium difficile (GPR) toxin,    increase sensitivity; toxin testing for test-of-cure is   Other risk factors for C difficile-induced colitis are
 Clostridium perfringens (GPR),      not recommended. Fecal WBCs are present in                 GI manipulations, advanced age, female sex,
 Staphylococcus aureus (GPC),        30–50% of cases. The toxin is very labile and              inflammatory bowel disease, HIV, chemotherapy,
 Klebsiella oxytoca (GNR).           can be present in infants with no disease.                 and renal disease.




                                                                                                                                                         Antibiotic-Associated Colitis
                                    Stool culture is not recommended because non-              C difficile nosocomial infection can be controlled by
                                     toxigenic strains occur.                                   handwashing.
                                    Colonoscopy and visualization of characteristic            Antibiotic-associated diarrhea may include un-




                                                                                                                                                                                         ABDOMEN
                                     1–5 mm raised yellow plaques provides the most             complicated diarrhea, colitis, or pseudomembranous
                                     rapid diagnosis.                                           colitis. Only 10–20% of cases are caused by infec-
                                    However, an ultrasound appearance of grossly thick-         tion with C difficile. Most clinically mild cases are
                                     ened bowel wall with luminal narrowing or CT               due to functional disturbances of intestinal
                                     findings of thickened bowel wall, presence of an            carbohydrate or bile acid metabolism, to allergic
                                     “accordion” sign, heterogeneous contrast enhance-          and toxic effects of antibiotics on intestinal mucosa,
                                     ment pattern (“target sign”), pericolonic stranding,       or to their pharmacologic effects on motility.
                                     ascites, pleural effusion, and subcutaneous edema         Radiolog 1996;198:1.
                                     can suggest the diagnosis of pseudomembranous             Clin Infect Dis 1998;27:702.
                                     colitis.                                                  Dig Dis 1998;16:292.
                                                                                               Dis Colon Rectum 1998;41:1435.
                                                                                               J Antimicrob Chemother 1998;41 (Suppl C):29, 59.
                                                                                               Digestion 1999;60:91.
                                                                                               Hepatogastroenterology 1999;46:343.
Diarrhea in the HIV-Infected         Stool for stain for fecal leukocytes, culture (especially   Most patients with HIV infection will develop diar-
 Host                                 for salmonella, shigella, yersinia, and campylobac-         rhea at some point in their illness.
                                      ter), C difficile toxin, ova and parasite examination,      Cryptosporidium causes a chronic debilitating diar-
Same as Child-Adult Infectious        and AFB smear. Multiple samples are often                   rheal infection that rarely remits spontaneously and
 Colitis with addition of cyto-       needed.                                                     is still without effective treatment. Diarrhea seems
 megalovirus, cryptosporidium,       Proctosigmoidoscopy with fluid aspiration and                 to be the result of malabsorption and produces a




                                                                                                                                                         Diarrhea in HIV
 Isospora belli, microsporidia        biopsy is indicated in patients with chronic or             cholera-like syndrome.




                                                                                                                                                                           ABDOMEN
 (Enterocytozoon bieneusi),           recurrent diarrhea or in diarrhea of unknown cause         Between 15% and 50% of HIV-infected patients
 C difficile, Giardia intestinalis,    for smears of aspirates (may show organisms) and            with diarrhea have no identifiable pathogen.
 Mycobacterium avium-                 histologic examination and culture of tissue.              J Clin Microbiol 1995;33:745.
 intracellulare complex (AFB),       Rectal and jejunal biopsies may be necessary, espe-         Gastroenterology 1996;111:1724.
 herpes simplex (HSV). Ent-           cially in patients with tenesmus or bloody stools.         Gastrointest Endosc Clin North Am 1998;8:857.
 amoeba histolytica, ?HIV.            Need modified acid-fast stain for cryptosporidium.          J Infect Dis 1999;179(Suppl 3):S454.
                                      Intranuclear inclusion bodies on histologic exam           Am J Gastroenterol 1999;94:596.
                                      suggest CMV.                                               Arch Intern Med 1999;159:1473.
                                     Immunodiagnosis of giardia, cryptosporidium, and
                                      E histolytical cysts in stool is highly sensitive and
                                      specific.




                                                                                                                                                                                     Microbiology: Test Selection
                                                                                                                                                                                     225
                                                                                                                                                                          226
              Organism                          Specimen /Diagnostic Tests                                     Comments
Peritonitis                         Peritoneal fluid sent for WBC (> 1000/µL in SPB,      In nephrotic patients, Enterobacteriaceae and
                                     > 100/µL in CAPD) with PMN (≥ 250/µL SBP and S aureus are most frequent. In cirrhotics, 69% of




                                                                                                                                                                          Pocket Guide to Diagnostic Tests
Spontaneous or primary (associated secondary peritonitis, 50% PMN in CAPD); total         cases are due to Enterobacteriaceae. Cirrhotic
 with nephrosis or cirrhosis) peri-  protein (> 1gd/L); glucose (< 50 mg/dL) and lactate patients with low ascitic fluid protein levels
 tonitis (SBP): Enterobacteriaceae   dehydrogenase (> 225 units/mL) in secondary; pH      (≤ 1 g/dL) and high bilirubin level or low platelet
 (GNR) (69%), S pneumoniae           (< 7.35 in 57% for SBP). Gram stain (22–77% for      count are at high risk of developing spontaneous
 (GPC), group A streptococcus        SBP), and culture of large volumes often in blood    bacterial peritonitis.
 (GPC), S aureus (GPC), anaer-       culture bottles. (See Ascitic fluid profiles, p 365.) “Bacterascites,” a positive ascitic fluid culture with-
 obes (5%).                         Blood cultures for bacteria positive in 75% of SBP    out an elevated PMN count, is seen in 8% of cases
Secondary (bowel perforation,        cases.                                               of SBP and probably represents early infection.
 hospital-acquired, or antecedent Catheter-related infection is associated with a WBC In secondary peritonitis, factors influencing the inci-




                                                                                                                                                                ABDOMEN
                                                                                                                                                  Peritonitis
 antibiotic therapy): Enterobacte-   > 500/µL.                                            dence of postoperative complications and death
 riaceae, enterococcus (GPC),                                                             include age, presence of certain concomitant dis-
 bacteroides sp (GNR), Pseudo-                                                            eases, site of origin of peritonitis, type of admis-
 monas aeruginosa (GNR)                                                                   sion, and the ability of the surgeon to eliminate the
 (3–15%).                                                                                 source of infection.
Chronic ambulatory peritoneal                                                            Clin Infect Dis 1998;27:669.
 dialysis (CAPD): Coagulase-                                                             Eur J Clin Microbiol Infect Dis 1998;17:542.
 negative staphylococci (GPC)                                                            J Am Soc Nephrol 1998;9:1956.
 (43%), S aureus (14%), strepto-                                                         Langenbecks Arch Surg 1999;384:24.
 coccus sp (12%), Enterobacteri-                                                         Gastroenterology 1999;117:414.
 aceae (14%), Pseudomonas
 aeruginosa, candida (2%),
 aspergillus (rare), cryptococcus
 (rare).
Tuberculous Peritonitis/       Ascitic fluid for appearance (clear, hemorrhagic or      Infection of the intestines can occur anywhere along
 Enterocolitis                  chylous), RBCs (can be high), WBCs (> 1000/µL,          the GI tract but occurs most commonly in the ileo-
                                > 70% lymphs), protein (> 2.5 g/dL), serum/ascites      cecal area or mesenteric lymph nodes. It often com-
Mycobacterium tuberculosis      albumin gradient (<1.1), LDH (> 90 units/L), AFB        plicates pulmonary infection. Peritoneal infection
 (MTb, AFB, acid-fast beaded    culture (<50% positive). (See Ascitic fluid profiles,     usually is an extension of intestinal disease. Symp-
 rods).                         p 365.) With coexistent chronic liver disease, pro-     toms may be minimal even with extensive disease.
                                tein level and SAAG are usually not helpful, but       In the US, 29% of patients with abdominal tubercu-




                                                                                                                                               Tuberculous Peritonitis/Enterocolitis
                                LDH > 90 units/L is a useful predictor.                 losis have a normal chest x-ray.
                               Culture or AFB smear from other sources (especially     Presence of AFB in the feces does not correlate with
                                from respiratory tract) can help confirm diagnosis.      intestinal involvement.
                               Abdominal ultrasound may demonstrate free or loc-       Acta Radiologica 1996;37:517.
                                ulated intra-abdominal fluid, intra-abdominal           AJR Am J Roentgenol 1996;167:743.




                                                                                                                                                                                       ABDOMEN
                                abscess, ileocecal mass, and retroperitoneal lymph-    Am J Med 1996;100:179.
                                adenopathy. Ascites with fine, mobile septations        Rays 1998;23:115.
                                shown by ultrasound and peritoneal and omental         Eur J Surg 1999;165:158.
                                thickening detected by CT strongly suggest tuber-      South Med J 1999;92:406.
                                culous peritonitis.
                               Marked elevations of serum CA 125 have been




                                                                                                                                                                                                 Microbiology: Test Selection
                                noted; levels decline to normal with anti-
                                tuberculous therapy.
                               Diagnosis of enterocolitis rests on biopsy of colonic
                                lesions via endoscopy if pulmonary or other extra-
                                pulmonary infection cannot be documented.
                               Diagnosis is best confirmed by laparoscopy with
                                peritoneal biopsy and culture.
                               Operative procedure may be needed to relieve
                                obstruction or for diagnosis.




                                                                                                                                                                                                 227
                                                                                                                                                                                  228
            Organism                              Specimen /Diagnostic Tests                                           Comments
Diverticulitis                       Identification of organism is not usually sought.           Pain usually is localized to the left lower quadrant
                                     Ultrasonography (US) or flat and upright x-rays of            because the sigmoid and descending colon are the




                                                                                                                                                                                  Pocket Guide to Diagnostic Tests
Enterobacteriaceae (GNR), bac-        abdomen are crucial to rule out perforation (free air       most common sites for diverticula.
 teroides sp (GNR), enterococcus      under diaphragm) and to localize abscess (air-fluid        It is important to rule out other abdominal disease
 (GPC in chains).                     collections).                                               (eg, colon carcinoma, Crohn’s disease, ischemic
                                     Barium enema can (82%) show presence of divertic-            colitis).




                                                                                                                                                       Diverticulitis
                                      ula. Avoid enemas in acute disease because increased      Acta Radiologica 1997;38:313.
                                      intraluminal pressure may cause perforation.              Radiology 1997;205:503.
                                     Ultrasound (85%) and CT (79–98%) have greater              Dis Colon Rect 1998;41:1023.
                                      accuracy in the evaluation of patients with divertic-     Radiology 1998;208:611.
                                      ulitis. Specificities of barium enema, ultrasound,         N Engl J Med 1998;338:1521.
                                      and CT are 81–84%. Thin-section helical CT is             AJR Am J Roentgenol 1999;172:601.
                                      also able to reveal inflamed diverticula in acute          Surg Endosc 1999;13:430.
                                      diverticulitis by demonstrating an enhancing pat-




                                                                                                                                                                        ABDOMEN
                                      tern of the colonic wall. Urinalysis will reveal
                                      urinary tract involvement, if present.
Liver Abscess                        CT scan with contrast and ultrasonography are the          Travel to and origin in an endemic area are impor-
                                      most accurate tests for the diagnosis of liver abscess.    tant risk factors for amebic liver abscess.
Usually polymicrobial: Entero-       Antibodies against E histolytica should be obtained on     60% of patients have a single lesion; 40% have
 bacteriaceae, especially klebsiella all patients. (See Amebic serology, p 50.) Complete         multiple lesions.
 (GNR), enterococcus (GPC in          removal of abscess material obtained via surgery or       Biliary tract disease is the most common underlying




                                                                                                                                                       Liver Abscess
 chains), bacteroides sp (GNR),       percutaneous aspiration is recommended for culture         disease, followed by malignancy (biliary tract or
 actinomyces (GPR), S aureus          and direct examination for E histolytica. E histolytica    pancreatic), colonic disease (diverticulitis), dia-
 (GPC in clusters), candida sp,       has been described with modern techniques as a com-        betes mellitus, liver disease, and alcoholism.
 Entamoeba histolytica.               plex of two species, the commensal parasite E dispar      Clin Radiol 1997;52:912.
                                      and the pathogenic parasite. Stool for antigen detec-     South Med J 1997;90:23.
                                      tion is sensitive and can distinguish the two species.    Ann Emerg Med 1999;34:351.
                                     Chest x-ray is often useful with raised hemi-              World J Surg 1999;23:102.
                                      diaphragm, right pleural effusion, or right basilar       West J Med 1999;170:104.
                                      atelectasis in 41% of patients.
                                     Elevation of serum alkaline phosphatase level in 78%.
Cholangitis/Cholecystitis           Ultrasonography is the best test to quickly demon-      90% of cases of acute cholecystitis are calculous,
                                     strate gallstones or phlegmon around the gallblad-      10% are acalculous. Risk factors for acalculous
Enterobacteriaceae (GNR) (68%),      der or dilation of the biliary tree. (See Abdominal     disease include prolonged illness, fasting, hyper-
 enterococcus (GPC in chains)        Ultrasound, p 258.)                                     alimentation, HIV infection, and carcinoma of the
 (14%), Pseudomonas aeruginosa      CT scanning is useful in cholangitis in detecting the    gallbladder or bile ducts.




                                                                                                                                                    Cholangitis/Cholecystitis
 (GNR), bacteroides (GNR)            site and cause of obstruction but may fail to detect   Biliary obstruction and cholangitis can develop
 (10%), clostridium sp (GPR)         stones in the common bile duct. In acute cholecys-      before biliary dilation is detected.
 (7%), microsporidia (Enterocyto-    titis, ultrasonography is superior to MR cholangi-     Common bile duct obstruction secondary to tumor




                                                                                                                                                                                ABDOMEN
 zoon bieneusi), Ascaris lumbri-     ography in evaluating gallbladder wall thickening.      or pancreatitis seldom results in infection (0–15%).
 coides, Opisthorchis viverrini,     However, MR cholangiography is superior to ultra-      There is a high incidence of acalculous cholecystitis
 O felineus, Clonorchis sinensis,    sound in depicting cystic duct and gallbladder neck     in AIDS patients with CD4 counts < 200/µL, due to
 Fasciola hepatica, Echinococcus     stones and in evaluating cystic duct obstruction.       cryptosporidium, cytomegalovirus, yeast, tubercu-
 granulosus, E multilocularis,      Radionuclide scans can demonstrate cystic duct           losis, and Mycobacterium avium-intracellulare.
 hepatitis C virus, hepatitis B      obstruction. (See p 266.)                               Observation of gallbladder contraction on hepa-
 virus, cytomegalovirus.            Blood cultures for bacteria.                             tobiliary scintigraphy after intravenous cholecys-
                                                                                             tokinin excludes acalculous cholecystitis.
                                                                                            Radiology 1998;209:781.
                                                                                            Mayo Clin Proc 1998;73:473, 479.




                                                                                                                                                                                          Microbiology: Test Selection
                                                                                            Radiology 1999;211:373.




                                                                                                                                                                                          229
                                                                                                                                                                                            230
          Organism                             Specimen /Diagnostic Tests                                        Comments
Urinary Tract Infection           Urinalysis and culture reveal the two most important    Most men with urinary tract infections have a func-
 (UTI)/Cystitis/Pyuria-Dysuria     signs: bacteriuria and pyuria (> 10 WBCs/µL). 30%       tional or anatomic genitourinary abnormality.




                                                                                                                                                                                            Pocket Guide to Diagnostic Tests
 Syndrome                          of patients have hematuria. Cystitis (95%) is diag-    In catheter-related UTI, cure is unlikely unless the
                                   nosed by ≥ 102 CFU/mL of bacteria; other urinary        catheter is removed. In asymptomatic catheter-
Enterobacteriaceae (GNR, espe-     infections (90%) by ≥ 105 CFU/mL. Culture is gen-       related UTI, antibiotics should be given only if
 cially E coli), Chlamydia tra-    erally not necessary for uncomplicated cystitis in      patients are at risk for sepsis (old age, underlying




                                                                                                                                                  Urinary Tract Infection
                                                                                                                                                                            GENITOURINARY
 chomatis, Staphylococcus          women. However, pregnant women should be                disease, diabetes mellitus, pregnancy).
 saprophyticus (GPC) (in young     screened for asymptomatic bacteriuria and              Up to one-third of cases of acute cystitis have
 women), enterococcus (GPC),       promptly treated.                                       “silent” upper tract involvement.
 candida sp (yeast), N gonor-     Both Gram stain for bacteria and dipstick analysis      Infect Dis Clin North Am 1997;11:13
 rhoeae (GNCB), HSV, adeno-        for nitrite and leukocyte esterase perform similarly   Infect Dis Clin North Am 1997;11:609.
 virus, Corynebacterium            in detecting UTI in children and are superior to       Pediatrics 1999;103(4 Part 1):843.
 glucuronolyticum (GPR), Urea      microscopic analysis for pyuria.                       Urol Clin North Am 1999;26:821.
 plasma, urealyticum (GPR).       Intravenous pyelogram and cystocopy should be per-      Nephrol Dial Transplant 1999;14:2746.
                                   formed in women with recurrent or childhood            Am J Med 1999;106:636.
                                   infections, all young boys with UTI, men with          Postgrad Med 1999;105:181.
                                   recurrent or complicated infection, and patients       BMJ 1999;318:770.
                                   with symptoms suggestive of obstruction or renal
                                   stones. (See Intravenous pyelogram, p 273.)
Prostatitis                       Urinalysis shows pyuria.                                 Acute prostatitis is a severe illness characterized by
                                  Urine culture usually identifies causative organism.       fever, dysuria, and a boggy or tender prostate.
Acute and Chronic: Enterobacteri- Prostatic massage is useful in chronic prostatitis to    Chronic prostatitis often has no symptoms of dysuria
 aceae (GNR), pseudomonas sp       retrieve organisms but is contraindicated in acute       or perineal discomfort and a normal prostate




                                                                                                                                                                  GENITOURINARY
 (GNR), enterococcus (GPC in       prostatitis (it may cause bacteremia). Bacteriuria is    examination.
 chains), cytomegalovirus (CMV). first cleared by antibiotic treatment. Then urine cul-     Nonbacterial prostatitis (prostatodynia) represents




                                                                                                                                                    Prostatitis
                                   tures are obtained from first-void, bladder, and          90% of prostatitis cases. Its etiology is unknown,
                                   post-prostatic massage urine specimens. A higher         although chlamydia antigen can be found in up to
                                   organism count in the post-prostatic massage speci-      25% of patients.
                                   men localizes infection to the prostate (91%).          Int J STD AIDS 1997;8:475.
                                                                                           Clin Microbiol Rev 1998;11:604.
                                                                                           Int J Clin Pract 1998;52:540.
                                                                                           Am J Med 1999;106:327.
                                                                                           Sex Transm Infect 1999;75(Suppl 1):S46.
                                                                                           Urol Clin North Am 1999;26:737.




                                                                                                                                                                                  Microbiology: Test Selection
                                                                                                                                                                                  231
                                                                                                                                                                                          232
          Organism                              Specimen /Diagnostic Tests                                        Comments
Pyelonephritis                      Urine culture is indicated when pyelonephritis is        Patients usually present with fever, chills, nausea,
                                     suspected.                                               vomiting, and costovertebral angle tenderness.




                                                                                                                                                                                          Pocket Guide to Diagnostic Tests
Acute, uncomplicated (usually       Urinalysis will usually show pyuria (≥ 5 WBC/hpf)        20–30% of pregnant women with untreated bacteri-
 young women): Enterobacteri-        and may show WBC casts.                                  uria develop pyelonephritis.
 aceae (especially E coli) (GNR). Blood cultures for bacteria if sepsis is suspected. In     Brit J Urol 1998;81:360.




                                                                                                                                                    Pyelonephritis
Complicated (older women, men;       uncomplicated pyelonephritis, ultrasonography is        Int J Antimicrob Ag 1999;11:257.
 post-catheterization, obstruction,  not necessary. In severe cases, however, ultrasound     Clin Obstet Gynecol 1998;41:515.
 post-renal transplant): Entero-     is the optimal procedure for ruling out urinary tract   Urol Clin North Am 1999;26:753.
 bacteriaceae (especially E coli),   obstruction, pyonephrosis, and calculi. Doppler




                                                                                                                                                                          GENITOURINARY
 Pseudomonas aeruginosa (GNR), ultrasonography (88%) has a specificity of 100%
 enterococcus (GPC), Staphylo-       for acute pyelonephritis.
 coccus saprophyticus (GPC).        Intravenous pyelogram in patients with recurrent
                                     infection will show irregularly outlined renal pelvis
                                     with caliectasis and cortical scars. (See Intravenous
                                     pyelogram, p 273.)
Perinephric Abscess                 CT scan with contrast is more sensitive than ultra-      Most perinephric abscesses are the result of exten-




                                                                                                                                                    Perinephric Abscess
Associated with staphylococcal       sound in imaging abscess and confirming diagno-           sion of an ascending urinary tract infection. Often
 bacteremia: Staphylococcus          sis. (See Abdominal CT, p 259.)                          they are very difficult to diagnose.
 aureus (GPC).                      Urinalysis may be normal or may show pyuria.             They should be considered in patients who fail to
Associated with pyelonephritis:     Urine culture (positive in 60%).                          respond to antibiotic therapy, in patients with
 Enterobacteriaceae (GNR), can-     Blood cultures for bacteria (positive in 20– 40%).        anatomic abnormalities of the urinary tract, and in
 dida sp (yeast), coagulase-        Bacterial culture of abscess fluid via needle aspira-      patients with diabetes mellitus.
 negative staphylococci (GPC).       tion or drainage (percutaneous or surgical).            Hosp Pract (Off Ed) 1997;32(6):40.
                                                                                             Infect Dis Clin North Am 1997;11:663.
Urethritis (Gonococcal and      Urethral discharge collected with urethral swab usu-        About 50% of patients with GC will have
 Nongonococcal)                  ally shows ≥ 4 WBCs per oil immersion field, Gram            concomitant NGU infection.
                                 stain (identify gonococcal organisms as gram-              Always treat sexual partners. Recurrence may be
Gonococcal (GC): Neisseria gon-  negative intracellular diplococci), PMNs (in GC,            secondary to failure to treat partners. Half of the
 orrhoeae (GNDC).                > 95% of WBCs are PMNs, in NGU usually                      cases of nongonococcal urethritis (NGU) are not
Nongonococcal (NGU): Chlamydia <80% are PMNs).                                               due to Chlamydia trachomatis; frequently, no
 trachomatis (50%), Ureaplasma Urethral discharge for culture (80%) or nucleic acid          pathogen can be isolated.




                                                                                                                                                    Urethritis
 urealyticum, Trichomonas vagi-  assay (97%) for GC (usually not needed for diag-           Persistent or recurrent episodes with adequate treat-
 nalis, herpes simplex (HSV),    nosis); urine (80–92%) or urethral discharge (97%)          ment of patient and partners may warrant further
 Mycoplasma genitalium,          for detection of C trachomatis by nucleic acid              evaluation for other causes (eg, prostatitis).
 unknown (35%).                  amplification or wet mount for T vaginalis. Culture         MMWR Morb Mortal Wkly Rep 1998;47(RR-1):1.
                                 or nonamplified assays are considerably less sensi-         Dermatol Clinic 1998;16:723.




                                                                                                                                                                            GENITOURINARY
                                 tive for diagnosis of C trachomatis.                       Sex Transm Infect 1999;75(Suppl 1):S9
                                VDRL should be checked in all patients because of           Aust Fam Physician 1999;28:333.
                                 high incidence of associated syphilis.                     Clin Infect Dis 1999;28(Suppl 1):S66.
                                                                                            FEMS Immunol Med Microbiol 1999;24:437.
Epididymitis/Orchitis               Urinalysis may reveal pyuria. Patients aged >35 years   Testicular torsion is a surgical emergency that is
                                     will often have midstream pyuria and scrotal edema.     often confused with orchitis or epididymitis.




                                                                                                                                                                                            Microbiology: Test Selection
Age <35 years, homosexual men: Culture urine and expressible urethral discharge             Sexual partners should be examined for signs of
 Chlamydia trachomatis, N gon-       when present.                                           sexually transmitted diseases.




                                                                                                                                                    Epididymitis/Orchitis
 orrhoeae (GNDC).                   Prostatic secretions for Gram stain and bacterial       In non-sexually transmitted disease, evaluation for
Age >35 years, or children: Entero- culture are helpful in older patients.                   underlying urinary tract infection or structural
 bacteriaceae (especially E coli)   When testicular torsion is considered, Doppler           defect is recommended.
 (GNR), pseudomonas sp (GNR),        ultrasound or radionuclide scan can be useful          Clin Nucl Med 1996;21:479.
 salmonella (GNR), Haemophilus       in diagnosis.                                          J Urol 1997;158:2158.
 influenzae (GNCB), varicella        Ultrasonography in tuberculous epididymitis shows       J Clin Ultrasound 1997;25:390.
 (VZV), mumps.                       enlargement of the epididymis (predominantly in        Clin Infect Dis 1998;26:942.
Immunosuppression: H influenzae, the tail) and marked heterogeneity in texture. Other        Sex Transm Infect 1999;75(Suppl 1):S51.
 Mycobacterium tuberculosis          sonographic findings include a hypoechoic lesion        BJU Int 1999;84:827.
 (AFB), candida sp (yeast),          of the testis with associated sinus tract or extra-




                                                                                                                                                                                            233
 cytomegalovirus (CMV).              testicular calcifications.
                                                                                                                                                                                       234
           Organism                            Specimen /Diagnostic Tests                                     Comments
Vaginitis/Vaginosis               Vaginal discharge for appearance (in candidiasis,      Bacterial vaginosis results from massive overgrowth
                                   area is pruritic with thick “cheesy” discharge: in     of anaerobic vaginal bacterial flora (especially




                                                                                                                                                                                       Pocket Guide to Diagnostic Tests
Candida sp, Trichomonas vagi-      trichomoniasis, copious foamy discharge), pH           gardnerella).
 nalis, Gardnerella vaginalis      (about 4.5 for candida; 5.0–7.0 in trichomonas;       Serious infectious sequelae associated with bacterial
 (GPR), bacteroides (non-fragilis  5.0–6.0 with bacterial), saline (“wet”) preparation    vaginosis include abscesses, endometritis and
 (GNR), mobiluncus (GPR),          (motile organisms seen in trichomonas; cells cov-      pelvic inflammatory disease. There is also a danger
 peptostreptococcus (GPC),         ered with organisms—“clue” cells—in gardnerella;       of miscarriage, premature rupture of the mem-




                                                                                                                                                                       GENITOURINARY
                                                                                                                                                 Vaginitis/Vaginosis
 Mycoplasma hominis, groups A      yeast and hyphae in candida, “fishy” odor on addi-      branes, and premature labor.
 and B streptococci (GPC), herpes tion of KOH with gardnerella infection). Vaginal       Am J Obstet Gynecol 1991;165(4 Part 2):1161.
 simplex (HSV).                    fluid pH as a screening test for bacterial vaginosis   N Engl J Med 1997;337:1896.
                                   showed a sensitivity of 74.3%, but combined with      J Gen Intern Med 1998;13:335.
                                   clinical symptoms and signs its sensitivity           Pediatr Clin North Am 1999;46:733.
                                   increased to 81.3%. (See Vaginitis table, p 397.)     Int J Gynaecol Obstet 1999;66:143.
                                  Atrophic vaginitis is seen in postmenopausal           Sex Transm Infect 1999;75(Suppl 1):S16, S21.
                                   patients, often with bleeding, scant discharge,
                                   and pH 6.0–7.0
                                  Cultures for gardnerella are not useful and are not
                                   recommended. Culture for T vaginalis has greater
                                   sensitivity than wet mount. Culture for groups A
                                   and B streptococci and rare causes of bacterial
                                   vaginosis may be indicated.
Cervicitis, Mucopurulent       Cervical swab specimen for appearance (yellow or    Because of the danger of false-positive amplified
                                green purulent material), cell count (>10 WBCs per nucleic acid assays, culture is the preferred method
Chlamydia trachomatis (50%),    high-power oil immersion field and culture           in cases of suspected child abuse.
 N gonorrhoeae (GNDC) (8%).     (58–80%) or nucleic acid assay (93%) for GC;       In one study of pregnant women, a wet mount prepa-
                                urine for nucleic acid assay (93%) for GC; urine    ration of endocervical secretions with <10 PMNs
                                (80–92%) or cervical swab (97%) for detection of    per high-power field had a negative predictive




                                                                                                                                                       GENITOURINARY
                                C trachomatis by nucleic acid amplification. Cul-    value of 99% for gonococcus-induced cervicitis
                                ture (52%) or nonamplified assays (50–80%) are       and of 96% for C trachomatis-induced cervicitis. In




                                                                                                                                          Cervicitis
                                considerably less sensitive for diagnosis of        family planning clinics, however, a mucopurulent
                                C trachomatis.                                      discharge with > 10 PMNs/hpf had a low positive
                                                                                    predictive value of 29.2% for C trachomatis-
                                                                                    related cervicitis.
                                                                                   Mucopurulent discharge may persist for 3 months or
                                                                                    more even after appropriate therapy.
                                                                                   Curr Probl Dermatol 1996;24:110.
                                                                                   CMAJ 1998;158:41.
                                                                                   J Clin Microbiol 1998;36:1630.
                                                                                   Am J Obstet Gynecol 1999;181:283.




                                                                                                                                                                       Microbiology: Test Selection
                                                                                   Eur J Clin Microbiol Infect Dis 1999;18:142.




                                                                                                                                                                       235
                                                                                                                                                                                                        236
            Organism                            Specimen /Diagnostic Tests                                         Comments
Salpingitis/Pelvic Inflammatory      Gram stain and culture or amplified nucleic acid          PID typically progresses from cervicitis to endo-
 Disease (PID)                       assays of urethral or endocervical exudate.              metritis to salpingitis. PID is a sexually transmitted




                                                                                                                                                                                                        Pocket Guide to Diagnostic Tests
                                    Ultrasonographic findings include thickened fluid-          disease in some cases, not in others.
Usually polymicrobial: N gonor-      filled tubes, polycystic-like ovaries, and free pelvic   All sexual partners should be examined.
 rhoeae (GNDC), Chlamydia            fluid. MRI imaging findings for PID (95%) include         All IUDs should be removed.
 trachomatis, bacteroides, pepto-    fluid-filled tube, pyosalpinx, tubo-ovarian abscess,      Some recommend that all patients with PID be




                                                                                                                                                          Salpingitis
 streptococcus, G vaginalis, and     or polycystic-like ovaries and free fluid.                hospitalized.
 other anaerobes, Enterobacteri-     Laparoscopy supplemented by microbiologic tests         A strategy of identifying, testing, and treating
 aceae (GNR), streptococci (GPC      and fimbrial biopsy is the diagnostic standard for        women at increased risk for cervical chlamydial
 in chains), Mycoplasma hominis      PID. Transvaginal ultrasonography (81%) has a            infection can lead to a reduced incidence of PID.
 (debatable).                        lower specificity than MRI.                              N Engl J Med 1996;334:1362.




                                                                                                                                                                                        GENITOURINARY
                                    Laparoscopy is the most specific test to confirm the       Hum Reprod 1997;12(11 Suppl):121.
                                     diagnosis of PID.                                       Dermatol Clin 1998;16:747.
                                    VDRL should be checked in all patients because of        Lippincott Primary Care 1998;2:307.
                                     the high incidence of associated syphilis.              Radiology 1999;210:209.
                                                                                             Clin Infect Dis 1999;28 (Suppl 1):S29.
Chorioamnionitis/Endometritis      Amniotic fluid for Gram stain, leukocyte esterase,         Risk factors include bacterial vaginosis, preterm labor,




                                                                                                                                                        Chorioamnionitis/Endometritis
                                    glucose levels <10–20 mg/dL, and aerobic and              duration of labor, parity, internal fetal monitoring,
Group B streptococcus (GPC),        anaerobic culture; blood for culture. Sonographic        Infect Dis Clin North Am 1997;11:177;203.
 Escherichia coli (GNR), Listeria evaluation of fetus can be helpful, but findings            Semin Perinatol 1998;22:242.
 monocytogenes (GPR),               are nonspecific.                                          Pediatrics 1999;103:78.
 Mycoplasma hominis, Urea-
 plasma urealyticum, Gardnerella
 vaginalis, enterococci (GPC),
 viridans streptococci (GPC), bac-
 teroides (GNR), prevotella
 (GNR), and other anaerobic flora,
 Chlamydia trachomatis, group A
 streptococcus (GPC)
Osteomyelitis                        Blood cultures for bacteria are positive in about 60%.   Hematogenous or contiguous infection (eg, infected
                                     Cultures of percutaneous needle biopsy or open            prosthetic joint, chronic cutaneous ulcer) may lead
Staphylococcus aureus (GPC)           bone biopsy are needed if blood cultures are             to osteomyelitis in children (metaphyses of long
 (about 60% of all cases).            negative and osteomyelitis is suspected.                 bones) or adults (vertebrae, metaphyses of long
Infant: S aureus, Enterobacteri-     Imaging with bone scan or gallium/indium scan             bones).
 aceae (GNR), groups A and B          (sensitivity 95%, specificity 60–70%) can localize       Hematogenous osteomyelitis in drug addicts occurs
 streptococci (GPC).                  areas of suspicion. Technetium (99mTc)-Methylene         in unusual locations (vertebrae, clavicle, ribs).
Child (<3 years): H influenzae         diphosphonate (MDP) bone scan can suggest               In infants, osteomyelitis is often associated with
 (GNCB), S aureus, streptococci.      osteomyelitis days or weeks before plain bone            contiguous joint involvement.
Child (>3 years) to Adult: S aureus, films. Plain bone films are abnormal in acute cases        Acta Radiologica 1998;39:523.




                                                                                                                                                     Osteomyelitis
 Pseudomonas aeruginosa.              after about 2 weeks of illness (33%). Indium-           J Pediatr Orthop 1998;18:552.




                                                                                                                                                                     BONE
Postoperative: S aureus, Entero-      labeled WBC scan is useful in detecting abscesses.      J Comput Assist Tomogr 1998;22:437.
 bacteriaceae, pseudomonas sp        Ultrasound to detect subperiosteal abscesses and         Clin Radiol 1999;54:636.
 (GNR), Bartonella henselae           ultrasound-guided aspiration can assist in diagnosis    Pediatr Surg Int 1999;15:363.
 (GNR).                               and management of osteomyelitis. Ultrasound can
Joint prosthesis: Coagulase-          differentiate acute osteomyelitis from vaso-occlusive
 negative staphylococci, pep-         crisis in patients with sickle cell disease.
 tostreptococcus (GPC), Propi-       CT scan aids in detecting sequestra.




                                                                                                                                                                            Microbiology: Test Selection
 onibacterium acnes (GPR),           When bone x-rays and scintigraphy are negative,
 viridans streptococci (GPC in        MRI (98%) is useful for detecting early
 chains).                             osteomyelitis (specificity 89%), in defining extent,
                                      and in distinguishing osteomyelitis from cellulitis.
                                     Myelography, CT, or MRI is indicated to rule out
                                      epidural abscess in vertebral osteomyelitis.




                                                                                                                                                                            237
                                                                                                                                                                                             238
           Organism                                 Specimen /Diagnostic Tests                                         Comments
Bacterial/Septic Arthritis             Joint aspiration (synovial) fluid for WBCs (in non-       It is important to obtain synovial fluid and blood for
                                        gonococcal infection, mean WBC is 100,000/µL),            culture before starting antimicrobial treatment.




                                                                                                                                                                                             Pocket Guide to Diagnostic Tests
Infant (<3 months); S aureus            Gram stain (best on centrifuged concentrated speci-     Septic arthritis is usually hematogenously acquired.
 (GPC), Enterobacteriaceae              men; positive in one-third of cases), culture (non        Prosthetic joint and diminished host defenses sec-
 (GNR), Kingella kingae (GNCB),         gonococcal infection in adults [85–95%], DGI              ondary to cancer, HIV, liver disease, or hypogam-
 Haemophilus influenzae (GNCB).          [25%]). (See Synovial fluid profiles, p 389.)               maglobulinemia are common predisposing factors.
Child (3 months to 6 years):           Yield of culture is greatest if 10 mL of synovial fluid   Nongonococcal bacterial arthritis is usually monar-
 S aureus (35%), H influenzae,           is inoculated into a large volume of culture media,       ticular (and typically affects one knee joint).
 group A streptococcus (GPC),           such as a blood culture bottle, within 1 hour after     DGI is the most common cause of septic arthritis in
 (10%), Enterobacteriaceae (6%),        collection.                                               urban centers and is usually polyarticular with




                                                                                                                                                        Bacterial/Septic Arthritis
 Borrelia burgdorferi (Lyme).          Blood cultures for bacteria may be useful, especially      associated tenosynovitis.
Adult, STD not likely: S aureus         in infants; nongonococcal infection in adults           Radiol Clin North Am 1996;34:293.
 (40%), group A streptococcus           (50%); DGI (13%). B burgdorferi serology for            Rheumat Dis Clin North Am 1997;23:239.
 (27%), Enterobacteriaceae (23%),       Lyme disease.                                           Lancet 1998;351:197.




                                                                                                                                                                                     JOINT
 Streptobacillus moniliformis          Genitourinary, throat, or rectal culture: DGI may be     Am J Orthop 1999;28:168.
 (GNR), brucella (GNR),                 diagnosed by positive culture from a nonarticular       Radiology 1999;211:459.
 Mycobacterium marinum (AFB).           source and by a compatible clinical picture.            Pediatr Emerg Care 1999;15:40.
Adult, STD likely: N gonorrhoeae       In difficult cases, MRI can help differentiate septic
 (GNDC) (disseminated gonococ-          arthritis from transient synovitis.
 cal infection, DGI).
Prosthetic joint, postoperative or
 following intraarticular injection:
 Coagulase-negative staphylococci
 (40%), S aureus (20%), viridans
 streptococci (GPC in chains),
 enterococci (GPC), peptostrepto-
 coccus (GPC), Propionibacterium
 acnes (GPR), Enterobacteriaceae,
 pseudomonas sp.
Gas Gangrene                        Diagnosis should be suspected in areas of devital-   Gas gangrene occurs in the setting of a contaminated
                                     ized tissue when gas is discovered by palpation      wound. Clostridium perfringens produces potent
Clostridium perfringens (GPR),       (subcutaneous crepitation) or x-ray.                 exotoxins, including alpha toxin and theta toxin,




                                                                                                                                                 Gas Gangrene
 (80–95%), other clostridium sp.    Gram stain of foul-smelling, brown or blood-tinged    which depresses myocardial contractility, induces




                                                                                                                                                                MUSCLE
                                     watery exudate can be diagnostic with gram-positive shock, and causes direct vascular injury at the site
                                     rods and a remarkable absence of neutrophils.        of infection.
                                    Anaerobic culture of discharge is confirmatory.       Infections with enterobacter or E coli and anaerobic
                                                                                          infections can also cause gas formation. These
                                                                                          agents cause cellulitis rather than myonecrosis.
                                                                                         Postgrad Med 1996;99:217.
                                                                                         Clin Infect Dis 1999;28:159.
Impetigo                            Gram stain, culture, and smear for HSV and VZV         Impetigo neonatorum requires prompt treatment and
                                     antigen detection by direct fluorescent antibody        protection of other infants (isolation).
Infant (impetigo neonatorum):        (DFA) of scrapings from lesions may be useful in      Polymicrobial aerobic-anaerobic infections are pre-
 Staphylococcus (GPC).               differentiating impetigo from other vesicular or       sent in some patients.




                                                                                                                                                 Impetigo
                                                                                                                                                                SKIN
Nonbullous or “vesicular”: S pyo-    pustular lesions (HSV, VZV, contact dermatitis).      Patients with recurrent impetigo should have cul-
 genes (GPC), S aureus (GPC),        DFA smear can be performed by scraping the con-        tures of the anterior nares to exclude carriage of
 anaerobes.                          tents, base, and roof of vesicle and applying to       S aureus.




                                                                                                                                                                         Microbiology: Test Selection
Bullous: S aureus.                   glass slide. After fixing, the slide is stained with   Pediatr Dermatol 1997;14:192.
                                     direct fluorescent antibody (DFA) for identification    Practitioner 1998;242:405.
                                     of HSV or VZV.                                        Aust Fam Physician 1998;27:735.




                                                                                                                                                                         239
                                                                                                                                                                         240
              Organism                             Specimen /Diagnostic Tests                                    Comments
Cellulitis                              Skin culture: In spontaneous cellulitis, isolation Cellulitis has long been considered to be the result of
                                         of the causative organism is difficult. In trau-    an antecedent bacterial invasion with subsequent




                                                                                                                                                                         Pocket Guide to Diagnostic Tests
Spontaneous, traumatic wound: Polymi- matic and postoperative wounds, Gram stain            bacterial proliferation. However, the difficulty in
 crobial: S aureus (GPC), groups A, C, may allow rapid diagnosis of staphylococcal          isolating putative pathogens from cellulitic skin has
 and G streptococci (GPC), enterococci or clostridial infection. Culture of wound or        cast doubt on this theory. Predisposing factors for
 (GPC), Enterobacteriaceae (GNR),        abscess material after disinfection of the skin    cellulitis include diabetes mellitus, edema, periph-
 Clostridium perfringens (GPR),          site will almost always yield the diagnosis.       eral vascular disease, venous insufficiency, leg
 Clostridium tetani, pseudomonas sp     MRI can aid in diagnosis of secondary abscess       ulcer or wound, tinea pedis, dry skin, obesity, and
 (GNR) (if water exposure).              formation, necrotizing fasciitis, or pyomyositis. prior history of cellulitis.
Postoperative wound (not GI or GU):      Frozen section of biopsy specimen may be          Consider updating antitetanus prophylaxis for all
 S aureus, group A streptococcus,        useful.                                            wounds.
 Enterobacteriaceae, pseudomonas sp.                                                       In the diabetic, and in postoperative and traumatic
Postoperative wound (GI or GU):                                                             wounds, consider prompt surgical debridement for
 Must add bacteroides sp, anaerobes,                                                        necrotizing fasciitis. With abscess formation, surgi-




                                                                                                                                                     Cellulitis
 enterococcus (GPC), groups B or C




                                                                                                                                                                  SKIN
                                                                                            cal drainage is the mainstay of therapy and may be
 streptococci.
                                                                                            sufficient.
Diabetes mellitus: Polymicrobial:
                                                                                           Hemolytic streptococcal gangrene may follow minor
 S pyogenes, enterococcus, S aureus,
 Enterobacteriaceae, anaerobes.                                                             trauma and involves specific strains of streptococcus.
Bullous lesions, sea water contami-                                                        AJR Am J Roentgenol 1998;170:615.
 nated abrasion, after raw seafood con-                                                    Diagn Microbiol Infect Dis 1999;34:325.
 sumption: Vibrio vulnificus (GNR).                                                         Lippincott Primary Care Pract 1999;3:59.
Vein graft donor site: Streptococcus.                                                      BMJ 1999;318:1591.
Decubitus ulcers: Polymicrobial:
 S aureus, anaerobic streptococci,
 Enterobacteriaceae, pseudomonas
 sp, bacteroides sp.
Necrotizing fasciitis, type 1: Strepto-
 coccus, anaerobes, Enterobacteri-
 aceae; type 2: Group A streptococcus
 (hemolytic streptococcal gangrene).
Bacteremia of Unknown Source             Blood cultures are mandatory for all patients     Occult bacteremia affects approximately 5% of
                                          with fever and no obvious source of infection.    febrile children ages 2–36 months. In infants, the
Neonate <4 days): Group B strepto-        Often they are negative, especially in neonates. findings of an elevated total WBC count (> 15,000)
 coccus (GPC), E coli (GNR), kleb-       Cultures should be drawn at onset of febrile       and absolute neutrophil count (ANC > 10,000)
 siella (GNR), enterobacter (GNR),        episode. Culture should never be drawn from       were equally sensitive in predicting bacteremia, but
 S aureus (GPC), coagulase-negative       an IV line or from a femoral site.                the ANC was more specific. Predisposing factors in
 staphylococci (GPC).                    Culture and Gram stain of urine, wounds, and       adults include IV drug use, neutropenia, cancer,
Neonate (> 5 days): Add H influenzae       other potentially infected sites provide a more   diabetes mellitus, venous catheterization,
 (GNCB).                                  rapid diagnosis than blood cultures.              hemodialysis, and plasmapheresis.
Child (nonimmunocompromised):                                                              Catheter-related infection in patients with long-term




                                                                                                                                                   Bacteremia of Unknown Source
 H influenzae, S pneumoniae (GPDC),                                                          venous access (Broviac, Hickman, etc) may be
 N meningitidis (GNDC), S aureus.                                                           treated successfully without removal of the line,
Adult (IV drug use): S aureus or viri-                                                      but recurrence of bacteremia is frequent.
 dans streptococci (GPC).                                                                  Switching needles during blood cultures does not




                                                                                                                                                                                  BLOOD
Adult (catheter-related, “line” sepsis):                                                    decrease contamination rates and increases the risk
 S aureus, coagulase-negative staphy-                                                       of needle-stick injuries.
 lococci, Corynebacterium jeikeium                                                         Am J Clin Pathol 1998;109:221.
 (GPR), pseudomonas sp, candida sp,                                                        Pediatrics 1998;102(1 Part 1):67.




                                                                                                                                                                                          Microbiology: Test Selection
 Malassezia furfur (yeast).                                                                Ann Emerg Med 1998;31:679.
Adult (splenectomized): S pneumo-                                                          Infect Dis Clin North Am 1999;13:397.
 niae, H influenzae, N meningitidis.                                                        Infect Dis Clin North Am 1999;13:483.
Neutropenia (< 500 PMN): Enterobac-
 teriaceae, pseudomonas sp, S aureus,
 coagulase-negative staphylococci,
 viridans group streptococcus.
Parasites: Babesia, ehrlichia, plasmo-
 dium sp, filarial worms.
Immunocompromised: Bartonella sp
 (GNR), herpesvirus 8 (HHV8),
 Mycobacterium avium-intracellulare




                                                                                                                                                                                          241
 (AFB).
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                                                                              6
                            Diagnostic Imaging:
               Test Selection and Interpretation




                                      Sean Perini, MD, and Susan D. Wall, MD




        HOW TO USE THIS SECTION

        Information in this chapter is arranged anatomically from superior
        to inferior. It would not be feasible to include all available imaging tests
        in one chapter in a book this size, but we have attempted to summarize
        the essential features of those examinations that are most frequently
        ordered in modern clinical practice or those that may be associated with
        difficulty or risk. Indications, advantages and disadvantages, contra-
        indications, and patient preparation are presented. Costs of the studies
        are approximate and represent averages reported from several large
        medical centers.

                                      $ = < $250
                                     $$ = $250–$750
                                    $$$ = $750–$1000
                                   $$$$ = > $1000



                                            243
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
244   Pocket Guide to Diagnostic Tests

RISKS OF INTRAVENOUS CONTRAST STUDIES

While intravenous contrast is an important tool in radiology, it is not
without substantial risks. Minor reactions (nausea, vomiting, hives)
occur with an overall incidence between 1% and 12%. Major reactions
(laryngeal edema, bronchospasm, cardiac arrest) occur in 0.16 to 2 cases
per 1000 patients. Deaths have been reported in 1 170,000 to 1 40,000
cases. Patients with an allergic history (asthma, hay fever, allergy to
foods or drugs) are at increased risk. A history of reaction to contrast
material is associated with an increased risk of a subsequent severe re-
action. Prophylactic measures that may be required in such cases include
H1 and H2 blockers and corticosteroids.
     In addition, there is a risk of contrast-induced renal failure, which
is usually mild and reversible. Persons at increased risk for potentially
irreversible renal damage include patients with preexisting renal dis-
ease (particularly diabetics with high serum creatinine concentrations),
multiple myeloma, and severe hyperuricemia.
     In summary, intravenous contrast should be viewed in the same
manner as other medications—ie, risks and benefits must be balanced
before an examination using this pharmaceutical is ordered.
   Test                 Indications                      Advantages           Disadvantages/Contraindications              Preparation
HEAD        Evaluation of acute craniofacial        Rapid acquisition      Artifacts from bone may interfere with     Normal hydration.
             trauma, acute neurologic dysfunc-       makes it the modality detection of disease at the skull base     Sedation of agitated
Computed     tion (<72 hours) from suspected         of choice for trauma. and in the posterior fossa. Generally       patients.
 tomography intracranial or subarachnoid            Superb spatial          limited to transaxial views. Direct coro- Recent serum creati-
 (CT)        hemorrhage.                             resolution.            nal images of paranasal sinuses and        nine determination if
            Further characterization of intra-      Superior to MRI in      temporal bones are routinely obtained      intravenous contrast




                                                                                                                                                   CT
$$$          cranial masses identified by MRI         detection of hemor-    if patient can lie prone.                  is to be used.
             (presence or absence of calcium         rhage within the first Contraindications and risks: Contra-




                                                                                                                                                                Diagnostic Imaging: Test Selection and Interpretation
             or involvement of the bony              24– 48 hours.          indicated in pregnancy because of the
             calvarium).                                                    potential harm of ionizing radiation to
            Evaluation of sinus disease and                                 the fetus. See Risks of Intravenous
             temporal bone disease.                                         Contrast Studies, page 244.
HEAD         Evaluation of essentially all intra-   Provides excellent tis-   Subject to motion artifacts.




                                                                                                                                                         HEAD
                                                                                                                         Sedation of agitated
              cranial disease except those listed    sue contrast resolu-     Inferior to CT in the setting of acute      patients.
              above for CT.                          tion, multiplanar         trauma because it is insensitive to acute Screening CT or plain
Magnetic                                             capability.               hemorrhage, incompatible with traction radiograph images of
 resonance                                          Can detect flowing          devices, inferior in detection of bony     orbits if history sug-
 imaging                                             blood and cryptic vas-    injury and foreign bodies, and requires    gests possible metal-
 (MRI)                                               cular malformations.      longer imaging acquisition time.           lic foreign body in




                                                                                                                                                   MRI
                                                    Can detect demye-         Special instrumentation required for        the eye.
$$$$                                                 linating and dysmye-      patients on life support.
                                                     linating disease.        Contraindications and risks: Contra-
                                                    No beam-hardening          indicated in patients with cardiac pace-
                                                     artifacts such as can     makers, intraocular metallic foreign
                                                     be seen with CT.          bodies, intracranial aneurysm clips,
                                                    No ionizing radiation.     cochlear implants, and some artificial
                                                                               heart valves.




                                                                                                                                                                245
                                                                                                                                                                    246
   Test                  Indications                   Advantages           Disadvantages/Contraindications                Preparation
BRAIN        Evaluation of cerebral arteriovenous No ionizing radiation. Subject to motion artifacts.                Sedation of agitated
              malformations, intracranial         No iodinated contrast Special instrumentation required for          patients.




                                                                                                                                                                    Pocket Guide to Diagnostic Tests
Magnetic re- aneurysm, and blood supply of         needed.                patients on life support.                  Screening CT or plain
 sonance      vascular tumors as aid to operative                        Contraindications and risks: Contra-         radiograph images of




                                                                                                                                               MRA/MRV
 angiog-      planning (MRA).                                             indicated in patients with cardiac pace-    orbits if history sug-
 raphy/      Evaluation of dural sinus thrombo-                           makers, intraocular metallic foreign        gests possible metal-
 venogra-     sis (MRV).                                                  bodies, intracranial aneurysm clips,        lic foreign body in
 phy (MRA/                                                                cochlear implants, and some artificial       the eye.
 MRV)                                                                     heart valves.




                                                                                                                                                            BRAIN
$$$$
BRAIN         Confirmation of brain death.          Confirmation of brain Limited resolution.                          Sedation of agitated
                                                    death not impeded by Delayed imaging required with some           patients.
Brain scan                                          hypothermia or bar-   agents.                                    Premedicate with po-
 (radio-                                            biturate coma.       Cannot be used alone to establish diag-      tassium perchlorate




                                                                                                                                               Brain Scan
 nuclide)                                          Can be portable.       nosis of brain death. Must be used in       when using TcO4 in
                                                                          combination with clinical examination       order to block cho-
$$                                                                        or cerebral angiography to establish        roid plexus uptake.
                                                                          diagnosis.
                                                                         Contraindications and risks: Caution
                                                                          in pregnancy because of the potential
                                                                          harm of ionizing radiation to the fetus.
BRAIN           Evaluation of suspected dementia.    Provide functional     Limited resolution compared with MRI Requires lumbar
                Evaluation of medically refractory    information.           and CT.                                      puncture to deliver




                                                                                                                                                                    CENTRAL NERVOUS SYSTEM
Positron         seizures.                           Can localize seizure   Limited application in workup of demen- radiopharmaceutical.
 emission                                             focus prior to surgi-  tia due to low specificity of images and
 tomogra-                                             cal excision.          fact that test results do not alter clinical




                                                                                                                                                  Brain PET/SPECT
 phy (PET)/                                          Up to 82% positive      management.
 single pho-                                          predictive value for Contraindications and risks: Caution
 ton emission                                         Alzheimer’s demen-     in pregnancy because of potential harm
 (SPECT)                                              tia in appropriate     of ionizing radiation to the fetus.




                                                                                                                                                                                                 Diagnostic Imaging: Test Selection and Interpretation
 brain scan                                           clinical settings.
                                                     Provide cross-
$$$                                                   sectional images and
                                                      therefore improved




                                                                                                                                                                                         BRAIN
                                                      lesion localization
                                                      compared with
                                                      planar imaging
                                                      techniques.
BRAIN           Evaluation of hydrocephalus (par-    Provides functional   Requires multiple delayed imaging           Sedation of agitated
                 ticularly normal pressure), CSF      information.          sessions up to 48–72 hours after            patients.
Cisterno-        rhinorrhea or otorrhea, and         Can help distinguish   injection.                                 For suspected CSF




                                                                                                                                                  Cisternography
 graphy          ventricular shunt patency.           normal pressure      Contraindications and risks: Caution         leak, pack the
 (radio-                                              hydrocephalus from    in pregnancy because of the potential       patient’s nose or ears
 nuclide)                                             senile atrophy.       harm of ionizing radiation to the fetus.    with cotton pledgets
                                                     Can detect CSF leaks.                                              prior to administra-
$$                                                                                                                      tion of dose.
                                                                                                                       Must follow strict ster-
                                                                                                                        ile precautions for
                                                                                                                        intrathecal injection.




                                                                                                                                                                                                 247
                                                                                                                                                              248
   Test                   Indications                  Advantages           Disadvantages/Contraindications                  Preparation
NECK         Evaluation of the upper aero-        Provides excellent     Subject to motion artifacts, particularly     Sedation of agitated
              digestive tract.                     tissue contrast        those of carotid pulsation and                patients.




                                                                                                                                                              Pocket Guide to Diagnostic Tests
Magnetic     Staging of neck masses.               resolution.            swallowing.                                  Screening CT or plain
 resonance   Differentiation of lymphadenopathy Tissue differentiation Special instrumentation required for             radiograph images of
 imaging      from blood vessels.                  of malignancy or       patients on life support.                     orbits if history sug-
(MRI)        Evaluation of head and neck malig-    abscess from benign Contraindications and risks: Contra-             gests possible metal-
              nancy, thyroid nodules, parathyroid tumor often possible. indicated in patients with cardiac pace-        lic foreign body in
$$$$          adenoma, lymphadenopathy,           Sagittal and coronal    makers, intraocular metallic foreign          the eye.




                                                                                                                                                 MRI
              retropharyngeal abscess, brachial    planar imaging possi- bodies, intracranial aneurysm clips,
              plexopathy.                          ble. Multiplanar       cochlear implants, and some artificial
                                                   capability especially  heart valves.
                                                   advantageous regard-
                                                   ing brachial plexus.




                                                                                                                                                       NECK
                                                  No iodinated contrast
                                                   needed to distinguish
                                                   lymphadenopathy
                                                   from blood vessels.
NECK         Evaluation of carotid bifurcation    No ionizing radiation. Subject to motion artifacts, particularly     Sedation of agitated
              atherosclerosis, cervicocranial     No iodinated contrast     from carotid pulsation and swallowing.      patients.
Magnetic      arterial dissection.                 needed.                 Special instrumentation required for        Screening CT or plain
 resonance                                        MRA of the carotid        patients on life support.                   radiograph images of




                                                                                                                                                 MRA
 angiogra-                                         arteries can be a suf- Contraindications and risks: Contra-          orbits if history sug-
 phy (MRA)                                         ficient preoperative      indicated in patients with cardiac pace-    gests possible metal-
                                                   evaluation regarding makers, intraocular metallic foreign            lic foreign body in
$$$$                                               critical stenosis when bodies, intracranial aneurysm clips,          the eye.
                                                   local expertise exists. cochlear implants, and some artificial
                                                                            heart valves.
NECK         Evaluation of the upper aero-           Rapid.                  Adequate intravenous contrast enhance-    Normal hydration.
              digestive tract.                       Superb spatial           ment of vascular structures is manda-    Sedation of agitated
Computed     Staging of neck masses for patients      resolution.             tory for accurate interpretation.         patients.
 tomogra-     who are not candidates for MRI.        Can guide percuta-      Contraindications and risks: Contra-      Recent serum creati-




                                                                                                                                              CT
 phy (CT)    Evaluation of suspected abscess.         neous fine-needle        indicated in pregnancy because of the     nine determination.
                                                      aspiration of possible potential harm of ionizing radiation to
$$$$                                                  tumor or abscess.       the fetus. See Risks of Intravenous




                                                                                                                                                           NECK
                                                                              Contrast Studies, page 244.
NECK         Patency and morphology of arteries Can detect and moni- Technically demanding, operator-                 None.




                                                                                                                                                                     Diagnostic Imaging: Test Selection and Interpretation
              and veins.                         tor atherosclerotic     dependent.




                                                                                                                                              Ultrasound
Ultrasound   Evaluation of thyroid and           stenosis of carotid    Patient must lie supine and still for 1 hour.
 (US)         parathyroid.                       arteries noninvasively
             Guidance for percutaneous fine-      and without iodinated
$$            needle aspiration biopsy of neck   contrast.
              lesions.
THYROID      Determination as to whether a pal-      Noninvasive.           Cannot distinguish between benign and      None.
              pable nodule is a cyst or solid mass   No ionizing radiation. malignant lesions unless local invasion
Ultrasound    and whether single or multiple         Can be portable.        is demonstrated.




                                                                                                                                              Ultrasound
                                                                                                                                                           THYROID
 (US)         nodules are present.                   Can image in all       Technique very operator-dependent.
             Assessment of response to suppres-       planes.               Contraindications and risks: None.
$$            sive therapy.
             Screening patients with a history of
              prior radiation to the head and
              neck.
             Guidance for biopsy.




                                                                                                                                                                     249
                                                                                                                                                                                 250
   Test                    Indications                  Advantages            Disadvantages/Contraindications            Preparation
THYROID       Uptake indicated for evaluation of Demonstrates both         Substances interfering with test include Administration of
               clinical hypothyroidism, hyper-      morphology and          iodides in vitamins and medicines,       dose after a 4- to




                                                                                                                                                                                 Pocket Guide to Diagnostic Tests
Thyroid        thyroidism, thyroiditis, effects of  function.               antithyroid drugs, steroids, and         6-hour fast aids
 uptake and thyroid-stimulating and suppress- Can identify ectopic          intravascular contrast agents.           absorption.
 scan (radio- ing medications, and for calcula-     thyroid tissue and     Delayed imaging is required with iodides Discontinue all inter-




                                                                                                                                             Thyroid uptake and scan
 nuclide)      tion of therapeutic radiation        “cold” nodules that     (123I, 6 hours and 24 hours; 131I total  fering substances
               dosage.                              have a greater risk of body, 72 hours).                          prior to test, espe-




                                                                                                                                                                       THYROID
$$            Scanning indicated for above as       malignancy.            Test may not visualize thyroid gland in   cially thyroid-
               well as evaluation of palpable nod- Imaging of total body    subacute thyroiditis.                    suppressing medica-
               ules, mediastinal mass, and screen- with one dose (131I). Contraindications and risks: Not            tions: T3 (1 week),
               ing of patients with history of head                         advised in pregnancy because of the      T4 (4–6 weeks),
               and neck irradiation. Total body                             risk of ionizing radiation to the fetus  propylthiouracil
               scanning used for postoperative                              (iodides cross placenta and concentrate  (2 weeks).
               evaluation of thyroid metastases.                            in fetal thyroid). Significant radiation
                                                                            exposure occurs in total body scanning
                                                                            with 131I; patients should be instructed
                                                                            about precautionary measures by
                                                                            nuclear medicine personnel.
THYROID       Hyperthyroidism and some thyroid      Noninvasive alterna-   Rarely, radiation thyroiditis may occur      After treatment,
               carcinomas (papillary and follicu-    tive to surgery.       1–3 days after therapy.                      patients must isolate
Thyroid        lar types are amenable to treat-                            Hypothyroidism occurs commonly as a           all bodily secretions
 therapy       ment, whereas medullary and                                  long-term complication.                      from household
 (radio-       anaplastic types are not).                                  Higher doses that are required to treat       members.
 nuclide)                                                                   thyroid carcinoma may result in
                                                                            pulmonary fibrosis.




                                                                                                                                                 Radionuclide therapy
$$$                                                                        Contraindications and risks: Contra-
                                                                            indicated in pregnancy and lactation.




                                                                                                                                                                        THYROID

                                                                                                                                                                                      Diagnostic Imaging: Test Selection and Interpretation
                                                                            Contraindicated in patients with meta-
                                                                            static disease to the brain, because treat-
                                                                            ment may result in brain edema and
                                                                            subsequent herniation, and in those
                                                                            <20 years of age because of possible
                                                                            increased risk of thyroid cancer later in
                                                                            life. After treatment, a patient’s activi-
                                                                            ties are restricted to limit total exposure
                                                                            of any member of the general public
                                                                            until radiation level is ≤0.5 rem. High
                                                                            doses for treatment of thyroid carci-
                                                                            noma may necessitate hospitalization.
PARA-         Evaluation of suspected parathyroid Identifies hyperfunc- Small adenomas (<500 mg) may not be             Requires strict patient




                                                                                                                                                 Radionuclide scan
                                                                                                                                                                        PARATHYROID
 THYROID       adenoma.                            tioning tissue, which detected.                                      immobility during
                                                   is useful when plan- Contraindications and risks: Caution            scanning.
Parathyroid                                        ning surgery.         in pregnancy is advised because of the
 scan (radio-                                                            risk of ionizing radiation to the fetus.
 nuclide)

$$




                                                                                                                                                                                      251
                                                                                                                                                                       252
   Test                   Indications                 Advantages              Disadvantages/Contraindications           Preparation
CHEST        Evaluation of pleural and parenchy- Inexpensive.              Difficult to distinguish between causes of None.
              mal pulmonary disease, mediastinal Widely available.          hilar enlargement (ie, vasculature




                                                                                                                                                                       Pocket Guide to Diagnostic Tests
Chest         disease, cardiogenic and noncardio-                           versus adenopathy).
  radiograph genic pulmonary edema, congenital                             Contraindications and risks: Caution




                                                                                                                                            Chest radiograph
              and acquired cardiac disease.                                 in pregnancy because of the potential
$            Screening for traumatic aortic rup-                            harm of ionizing radiation to the fetus.
              ture (though angiogram is the stan-
              dard and spiral computed
              tomography is playing an increas-
              ing role).
             Evaluation of possible pneumotho-
              rax (expiratory upright film) or free




                                                                                                                                                               CHEST
              flowing fluid (decubitus views).
CHEST         Differentiation of mediastinal and   Rapid.                  Patient cooperation required for appro-   Preferably NPO for
               hilar lymphadenopathy from vas- Superb spatial               priate breath-holding.                    2 hours prior to
Computed       cular structures.                    resolution.            Generally limited to transaxial views.     study.
 tomogra-     Evaluation and staging of primary    Can guide percuta-      Contraindications and risks: Contra-      Normal hydration.
 phy (CT)      and metastatic lung neoplasm.        neous fine-needle        indicated in pregnancy because of the    Sedation of agitated
              Characterization of pulmonary         aspiration of possible potential harm of ionizing radiation to    patients.




                                                                                                                                            CT
$$$            nodules.                             tumor or abscess.       the fetus. See Risks of Intravenous      Recent serum creati-
              Differentiation of parenchymal ver-                           Contrast Studies, page 244.               nine determination.
               sus pleural process (ie, lung
               abscess versus empyema).
              Evaluation of interstitial lung dis-
               ease (1 mm thin sections), aortic
               dissection, and aneurysm.
CHEST         Evaluation of mediastinal masses.     Provides excellent tis- Subject to motion artifacts.                Sedation of agitated
              Discrimination between hilar ves-      sue contrast resolu- Contraindications and risks: Contra-           patients.
Magnetic       sels and enlarged lymph nodes.        tion and multiplanar    indicated in patients with cardiac pace-   Screening CT of the




                                                                                                                                                                               CHEST
 resonance    Tumor staging (especially when         capability.             makers, intraocular metallic foreign        orbits if history sug-




                                                                                                                                                  MRI
 imaging       invasion of vessels or pericardium No beam-hardening          bodies, intracranial aneurysm clips,        gests possible metal-
 (MRI)         is suspected).                        artifacts such as can   cochlear implants, and some artificial       lic foreign body in
              Evaluation of aortic dissection, aor- be seen with CT.         heart valves.                               the eye.
$$$$           tic aneurysm, congenital and         No ionizing radiation.
               acquired cardiac disease.




                                                                                                                                                                                       Diagnostic Imaging: Test Selection and Interpretation
LUNG          Evaluation of pulmonary embolism Noninvasive.                 Patients must be able to cooperate for       Current chest radio-
               or burn inhalation injury.         Provides functional        ventilation portion of the examination.      graph is mandatory
Ventilation- Preoperative evaluation of patients   information in pre-      There is a high proportion of inter-          for interpretation.
 perfusion     with chronic obstructive pulmonary operative assessment.      mediate probability studies in patients




                                                                                                                                                  Ventilation-perfusion scan
 scan (radio- disease and of those who are candi- Permits determination      with underlying lung disease. The like-
 nuclide)      dates for pneumonectomy.            of differential and       lihood of pulmonary embolism ranges
                                                   regional lung func-       from 20% to 80% in these cases.




                                                                                                                                                                               LUNG
V = $$
˙                                                  tion in preoperative     A patient who has a low probability scan
Q = $$
˙                                                  assessment.               still has a chance ranging from nil to
V+Q
˙ ˙                                               Documented pulmo-          19% of having a pulmonary embolus.
  = $$$–$$$$                                       nary embolism is         Contraindications and risks: Patients
                                                   extremely rare with       with severe pulmonary artery hyper-
                                                   normal perfusion          tension or significant right-to-left shunts
                                                   scan.                     should have fewer particles injected.
                                                                             Caution advised in pregnancy because
                                                                             of risk of ionizing radiation to the fetus.




                                                                                                                                                                                       253
                                                                                                                                                            254
   Test                   Indications                   Advantages             Disadvantages/Contraindications                Preparation
LUNG          Evaluation of clinically suspected   Rapid.                   Accuracy of spiral CT in diagnosing pul-     Large gauge intra-
               pulmonary embolism.                 Sensitivity and speci-    monary embolism depends on the size          venous access




                                                                                                                                                            Pocket Guide to Diagnostic Tests
Spiral com-                                         ficity values likely      of the pulmonary artery involved and         (minimum 20-gauge)
 puted                                              about 90% for the        the size of the thrombus. Sensitivity and    required.
 tomogra-                                           CT diagnosis of          accuracy of CT decreases for small,         Prebreathing oxygen
 phy (CT)                                           pulmonary emboli         subsegmental emboli (sensitivity rates       may help dyspneic
                                                    involving main to        of 53– 63% have been reported).              patients perform
$$$                                                 segmental artery        Respiratory motion artifacts can be a         adequate breath
                                                    branches in un-          problem in dyspneic patients. High-          hold.




                                                                                                                                                     LUNG
                                                                                                                                                CT
                                                    selected patients.       quality study requires breath-holding of    Normal hydration.
                                                   Overall, spiral CT        approximately 20 seconds.                   Preferably NPO for
                                                    sensitivity may be      Specific imaging protocol utilized which       2 hours prior to
                                                    higher than              limits diagnostic information for other      study.
                                                    ventilation/perfusion    abnormalities.                              Recent serum creati-
                                                    scintigraphy.           Contraindications and risks: Contra-          nine determination.
                                                                             indicated in pregnancy because of
                                                                             potential harm of ionizing radiation to
                                                                             fetus. See Risks of Intravenous Contrast
                                                                             Studies, page 244.
LUNG        Suspected pulmonary embolism         Remains the standard Invasive.                                      Ventilation/perfusion
             with equivocal results on            for diagnosis of acute Requires catheterization of the right heart scan for localization
Pulmonary    ventilation/perfusion scan or when and chronic pul-          and pulmonary artery.                       of right versus left




                                                                                                                                              Pulmonary angiography
 angiog-     definitive diagnosis especially       monary embolism.       Contraindications: Elevated pulmonary lung.
 raphy       important because of contraindica-                           artery pressure (> 70 mm Hg) or ele-       Electrocardiogram,
             tion to anticoagulation.                                     vated right ventricular end-diastolic       especially to exclude




                                                                                                                                                                      LUNG
$$$$        Arteriovenous malformation, pul-                              pressure (> 20 mm Hg). Pulmonary            left bundle branch
             monary sequestration, vasculitides,                          artery hypertension.                        block (in such cases,
             vascular occlusion by tumor or                                                                           temporary cardiac




                                                                                                                                                                             Diagnostic Imaging: Test Selection and Interpretation
             inflammatory disease.                                                                                     pacemaker should be
                                                                                                                      placed before the
                                                                                                                      catheter is intro-
                                                                                                                      duced into the pul-
                                                                                                                      monary artery).




                                                                                                                                                                             255
                                                                                                                                                     256
   Test                 Indications                 Advantages           Disadvantages/Contraindications          Preparation
BREAST    Screening for breast cancer in      Newer film screen        Detection of breast masses is more diffi- None.
            asymptomatic women: (1) every      techniques generate     cult in patients with radiographically




                                                                                                                                                     Pocket Guide to Diagnostic Tests
Mammo-      1–2 years between ages 40 and 49; lower radiation doses dense breasts.
 gram       (2) every year after age 50.       (0.1– 0.2 rad per film, Breast compression may cause patient
          If prior history of breast cancer,   mean glandular          discomfort.
$           mammogram should be performed dose). A 23% lower In a screening population, 9% of cancers
            yearly at any age.                 mortality has been      are detected by physical examination
          Indicated at any age for symptoms    demonstrated in         alone and are not detectable by




                                                                                                                                Mammogram
            (palpable mass, bloody discharge)  patients screened       mammography.




                                                                                                                                            BREAST
            or before breast surgery.          with combined mam- Contraindications and risks: Radiation
                                               mogram and physical from repeated mammograms can theo-
                                               exam compared to        retically cause breast cancer; however,
                                               physical exam alone. the benefits of screening mammograms
                                              In a screening popula- greatly outweigh the risks.
                                               tion, more than 40%
                                               of cancers are
                                               detected by mam-
                                               mography alone and
                                               cannot be palpated
                                               on physical exam.
HEART           Evaluation of atypical chest pain.   Highly sensitive for   The patient must be carefully monitored      Patient should be able
                Detection of presence, location, and detecting physiologi- during treadmill or pharmacologic              to exercise on a
Myocardial       extent of myocardial ischemia.       cally significant       stress— optimally, under the super-          treadmill.
  perfusion                                           coronary stenosis.     vision of a cardiologist.                   In case of severe pe-
  scan                                               Noninvasive.           False-positive results may be caused by       ripheral vascular
  (thallium                                          Able to stratify        exercise-induced spasm, aortic stenosis,     disease, severe pul-
  scan,                                               patients according to or left bundle branch block; false-           monary disease, or




                                                                                                                                                   Thallium scan
  technetium-                                         risk for myocardial    negative results may be caused by in-        musculoskeletal dis-
  99m meth-                                           infarction. Normal     adequate exercise, mild or distal dis-       order, pharmacologic




                                                                                                                                                                              Diagnostic Imaging: Test Selection and Interpretation
  oxyisobutyl                                         examination associ-    ease, or balanced diffuse ischemia.          stress with dipyri-
  isonitrile                                          ated with average     Contraindications and risk: Amino-            damole or other
  (sestamibi)                                         risk of cardiac death  phylline (inhibitor of dipyridamole) is a    agents may be used.
  scan, others)                                       or nonfatal myocar-    contraindication to the use of dipyrida-    Tests should be per-
                                                      dial infarction of     mole. Treadmill or pharmacologic             formed in the fasting




                                                                                                                                                                      HEART
 $–$$–$$$                                             <1% per year.          stress carries a risk of arrhythmia,         state.
(broad range)                                                                ischemia, infarct, and, rarely, death.      Patient should not
                                                                             Caution in pregnancy because of the          exercise between
                                                                             risk of ionizing radiation to the fetus.     stress and redistribu-
                                                                                                                          tion scans.
HEART         Evaluation of patients with ischemic Noninvasive.           Gated data acquisition may be difficult in Requires harvesting,
               heart disease and other cardio-     Ejection fraction is a  patients with severe arrhythmias.         labeling, and re-




                                                                                                                                                   Ventriculography
Radionuclide myopathies.                            reproducible index    Contraindications and risks: Recent        injecting the patient’s
 ventriculog- Evaluation of response to pharma-     that can be used to    infarct is a contraindication to exercise red blood cells.
 raphy         cologic therapy and effects of       follow course of dis- ventriculography (arrhythmia, ischemia, Sterile technique
 (multigated   cardiotoxic drugs.                   ease and response to   infarct, and rarely death may occur with required in handling
 acquisition                                        therapy.               exercise). Caution is advised in preg-    of red cells.
 [MUGA])                                                                   nancy because of the risk of ionizing
                                                                           radiation to the fetus.
$$–$$$–$$$$




                                                                                                                                                                              257
                                                                                                                                                                     258
   Test                     Indications               Advantages                   Disadvantages/Contraindications            Preparation
ABDOMEN       Assessment of bowel gas patterns   Inexpensive.                   Supine film alone is inadequate to rule out None.
               (eg, to distinguish ileus from    Widely available.               pneumoperitoneum (see indications).




                                                                                                                                                                     Pocket Guide to Diagnostic Tests
Abdominal      obstruction).                                                    Obstipation may obscure lesions.
 plain radio- To rule out pneumoperitoneum,                                     Contraindications and risks: Contra-
 graph         order an upright abdomen and                                      indicated in pregnancy because of the
 (KUB          chest radiograph (acute abdominal                                 risk of ionizing radiation to the fetus.




                                                                                                                                              KUB
 [kidneys,     series).
 ureters,
 bladder]




                                                                                                                                                           ABDOMEN
 x-ray)

$
ABDOMEN       Differentiation of cystic versus solid   Noninvasive.             Technique very operator-dependent.         NPO for 6 hours.
               lesions of the liver and kidneys,       No ionizing radiation.   Organs (particularly pancreas and distal
Ultrasound     intra- and extrahepatic biliary duc-    Can be portable.          aorta) may be obscured by bowel gas.




                                                                                                                                              Ultrasound
 (US)          tal dilation, cholelithiasis, gall-     Imaging in all planes.   Presence of barium obscures sound
               bladder wall thickness,                 Can guide percuta-        waves.
$$             pericholecystic fluid, peripancre-        neous fine-needle        Contraindications and risks: None.
               atic fluid and pseudocyst, primary        aspiration of tumor
               and metastatic liver carcinoma,          or abscess.
               hydronephrosis, abdominal aortic
               aneurysm, appendicitis, ascites.
ABDOMEN     Morphologic evaluation of all            Rapid.                 Barium or Hypaque, surgical clips, and     Preferably NPO for
             abdominal and pelvic organs.            Superb spatial          metallic prostheses can cause artifacts    4 –6 hours. Normal
Computed    Differentiation of intraperitoneal        resolution.            and degrade image quality.                 hydration.
 tomogra-    versus retroperitoneal disorders.       Not limited by over-   Contraindications and risks: Contra-       Opacification of
 phy (CT)   Evaluation of abscess, trauma,            lying bowel gas, as    indicated in pregnancy because of the      gastrointestinal tract
             mesenteric and retroperitoneal           with ultrasound.       potential harm of ionizing radiation to    with water-soluble
$$$–$$$$     lymphadenopathy, bowel wall             Can guide fine-needle    the fetus. See Risks of Intravenous        oral contrast
             thickening, obstructive biliary dis-     aspiration and percu-  Contrast Studies, page 244.                (Gastrografin).
             ease, pancreatitis, site of gastro-      taneous drainage                                                 Sedation of agitated




                                                                                                                                                                Diagnostic Imaging: Test Selection and Interpretation
             intestinal obstruction, appendicitis,    procedures.                                                       patients.
             peritonitis, and carcinomatosis,        Noncontrast spiral CT                                             Recent serum creati-
             splenic infarction, retroperitoneal      is superior to plain                                              nine determination.
             hemorrhage, aortoenteric fistula.         abdominal radiogra-




                                                                                                                                                      ABDOMEN
            Staging of renal cell carcinoma, car-     phy, ultrasound, and




                                                                                                                                                 CT
             cinomas of the gastrointestinal          intravenous urogra-
             tract, and metastatic liver disease.     phy in determination
            Sensitive in predicting that pancrea-     of size and location
             tic carcinoma is unresectable.           of renal and ureteral
            Excellent screening tool for evalua-      calculi.
             tion of suspected renal and ureteral
             calculi.
            Spiral CT angiography valuable in
             the evaluation of the aorta and its
             branches. Can provide preoperative
             assessment of abdominal aortic
             aneurysm to determine aneurysm
             size, proximal and distal extent,
             relationship to renal arteries, and
             presence of anatomic anomalies.




                                                                                                                                                                259
                                                                                                                                                                    260
   Test                    Indications                    Advantages             Disadvantages/Contraindications                Preparation
ABDOMEN      Clarification of CT findings when        Provides excellent tis-   Subject to motion artifacts.                NPO for 4– 6 hours.
              surgical clip artifacts are present.   sue contrast resolu-     Gastrointestinal opacification not yet       Intramuscular




                                                                                                                                                                    Pocket Guide to Diagnostic Tests
Magnetic     Differentiation of retroperitoneal      tion, multiplanar         readily available.                          glucagon to inhibit
 resonance    lymphadenopathy from blood ves- capability.                     Special instrumentation required for         peristalsis.
 imaging      sels or the diaphragmatic crus.       No beam-hardening          patients on life support.                  Sedation of agitated
 (MRI)       Preoperative staging of renal cell      artifacts such as can    Contraindications and risks: Contra-         patients.
              carcinoma.                             be seen with CT.          indicated in patients with cardiac pace-   Screening CT or plain




                                                                                                                                                          ABDOMEN
$$$$         Differentiation of benign nonhyper- No ionizing radiation.        makers, intraocular metallic foreign        radiograph images of




                                                                                                                                                    MRI
              functioning adrenal adenoma from                                 bodies, intracranial aneurysm clips,        orbits if history sug-
              malignant adrenal mass.                                          cochlear implants, and some artificial       gests possible metal-
             Complementary to CT in evaluation                                 heart valves.                               lic foreign body in
              of liver lesions (especially metasta-                                                                        the eye.
              tic disease and possible tumor
              invasion of hepatic or portal veins).
             Differentiation of benign cavernous
              hemangioma (> 2 cm in diameter)
              from malignancy.
ABDOMEN      Gastrointestinal hemorrhage that    Therapeutic emboliza- Invasive.                                    NPO for 4– 6 hours.
              does not resolve with conservative tion of gastrointesti- Patient must remain supine with leg         Good hydration to
Mesenteric    therapy and cannot be treated       nal hemorrhage is      extended for 6 hours following the pro- limit possible renal
 angio-       endoscopically.                     often possible.        cedure in order to protect the common       insult due to iodi-
 graphy      Localization of gastrointestinal                            femoral artery at the catheter entry site. nated contrast




                                                                                                                                            Mesenteric angiography
              bleeding site.                                            Contraindications and risks: Allergy to material.
$$$$         Acute mesenteric ischemia, intesti-                         iodinated contrast material may require Recent serum creati-




                                                                                                                                                                     ABDOMEN
              nal angina, splenic or other                               corticosteroid and H1 blocker or H2         nine determination,
              splanchnic artery aneurysm.                                blocker premedication. Contraindicated assessment of clot-




                                                                                                                                                                               Diagnostic Imaging: Test Selection and Interpretation
             Evaluation of possible vasculitis,                          in pregnancy because of the potential       ting parameters,
              such as polyarteritis nodosa.                              harm of ionizing radiation to the fetus.    reversal of anti-
             Detection of islet cell tumors not                          Contrast nephrotoxicity, especially with coagulation.
              identified by other studies.                                preexisting impaired renal function due Performed with con-
             Abdominal trauma.                                           to diabetes mellitus or multiple myel-      scious sedation.
                                                                         oma; however, any creatinine elevation Requires cardiac,
                                                                         following the procedure is usually          respiratory, blood
                                                                         reversible (see page 244).                  pressure, and pulse
                                                                                                                     oximetry monitoring.




                                                                                                                                                                               261
                                                                                                                                                                                262
     Test                  Indications                   Advantages              Disadvantages/Contraindications             Preparation
GI           Double-contrast barium technique       Good evaluation of       Aspiration of water-soluble contrast         NPO for 8 hours.
              demonstrates esophageal, gastric,      mucosa with double-      material may occur, resulting in severe




                                                                                                                                                                                Pocket Guide to Diagnostic Tests
Upper GI      and duodenal mucosa for evalua-        contrast examination.    pulmonary edema.
 study (UGI) tion of inflammatory disease and        No sedation required.    Leakage of barium from a perforation
              other subtle mucosal abnormalities. Less expensive than         may cause granulomatous inflammatory
$$           Single-contrast technique is suitable endoscopy.                 reaction.
              for evaluation of possible outlet                              Identification of a lesion does not prove
              obstruction, peristalsis, gastro-                               it to be the site of blood loss in patients




                                                                                                                                              UGI
              esophageal reflux and hiatal her-                                with gastrointestinal bleeding.
              nia, esophageal cancer and varices.                            Barium precludes endoscopy and body




                                                                                                                                                             GASTROINTESTINAL
             Water-soluble contrast (Gastrografin)                             CT examination.
              is suitable for evaluation of anasto-                          Retained gastric secretions prevent
              motic leak or gastrointestinal                                  mucosal coating with barium.
              perforation.                                                   Contraindications and risks: Contra-
                                                                              indicated in pregnancy because of the
                                                                              potential harm of ionizing radiation to
                                                                              the fetus.
GI           Barium fluoroscopic study for loca- Clarifies lesions noted Requires nasogastric or orogastric tube        Clear liquid diet for
              tion of site of intermittent partial  on more traditional     placement and manipulation to beyond       24 hours.
Enteroclysis small bowel obstruction.               barium examination      the ligament of Treitz.                   Colonic cleansing.
             Evaluation of extent of Crohn’s dis- of the small bowel.      Contraindications and risks: Radiation




                                                                                                                                              Enteroclysis
$$            ease or small bowel disease in       Best means of estab-     exposure is substantial, since lengthy
              patient with persistent gastro-       lishing small bowel     fluoroscopic examination is required.
              intestinal bleeding and normal        as normal.              Therefore, the test is contraindicated in
              upper gastrointestinal and           Controlled high rate of pregnant women and should be used
              colonic evaluations.                  flow of barium can       sparingly in children and women of
             Evaluation of metastatic disease to    dilate a partial        childbearing age.
              the small bowel.                      obstruction.
                                                                                                                                              Peroral pneumocolon
GI           Fluoroscopic evaluation of the ter- Best evaluation of the   Undigested food in the small bowel         Clear liquid diet for
              minal ileum by insufflating air per   terminal ileum.         interferes with the evaluation.            24 hours.
Peroral       rectum after orally ingested barium Can be performed        Contraindications and risk: Contra-
 pneumo-      has reached the cecum.               concurrently with       indicated in pregnancy because of the
 colon                                             upper GI series.        potential harm of ionizing radiation to
                                                                           the fetus.
$




                                                                                                                                                                    GASTROINTESTINAL
GI          Double-contrast technique for evalu- Good mucosal             Retained fecal material limits study.      Colon cleansing with




                                                                                                                                                                                       Diagnostic Imaging: Test Selection and Interpretation
             ation of colonic mucosa in patients evaluation.              Requires patient cooperation.               enemas, cathartic,
Barium       with suspected inflammatory bowel No sedation required.       Marked diverticulosis precludes evalua-     and clear liquid diet
 enema (BE) disease or neoplasm.                                           tion of possible neoplasm in that area.    (1 day in young
            Single-contrast technique for inves-                          Evaluation of right colon occasionally      patients, 2 days in




                                                                                                                                              Barium enema
$$           tigation of possible fistulous tracts,                         incomplete or limited by reflux of bar-     older patients).
             bowel obstruction, large palpable                             ium across ileocecal valve and over-      Intravenous glucagon
             masses in the abdomen, and diver-                             lapping opacified small bowel.              (which inhibits peri-
             ticulitis and for examination of                             Use of barium delays subsequent             stalsis) sometimes
             debilitated patients.                                         colonoscopy and body CT.                   given to distinguish
            Least invasive colon cancer screen-                           Contraindications and risks: Contra-        colonic spasm from
             ing technique.                                                indicated in patients with toxic mega-     a mass lesion.
                                                                           colon and immediately after full-
                                                                           thickness colonoscopic biopsy.




                                                                                                                                                                                       263
                                                                                                                                                                                           264
     Test                   Indications                   Advantages           Disadvantages/Contraindications             Preparation
GI             Water-soluble contrast for fluoro-     Water-soluble contrast Demonstrates only colonic morphologic      Colonic cleansing is
                scopic evaluation of sigmoid or       medium is evacuated features and not mucosal changes.             desirable but not




                                                                                                                                                                                           Pocket Guide to Diagnostic Tests
Hypaque         cecal volvulus, anastomotic leak      much faster than bar- Contraindications and risks: Contra-        always necessary.
 enema          or other perforation.                 ium because it does    indicated in patients with toxic mega-




                                                                                                                                               Hypaque enema
               Differentiation of colonic versus      not adhere to the      colon. Hypertonic solution may lead to
$$              small bowel obstruction.              mucosa. Therefore,     fluid imbalance in debilitated patients
               Therapy for obstipation.               Hypaque enema can      and children.
                                                      be followed immedi-
                                                      ately by oral inges-




                                                                                                                                                                        GASTROINTESTINAL
                                                      tion of barium for
                                                      evaluation of possi-
                                                      ble distal small
                                                      bowel obstruction.
GI             Evaluation of heartburn, regurgita-   Noninvasive and well Incomplete emptying of esophagus may         NPO for 4– 6 hours.
                tion, recurrent aspiration            tolerated.              mimic reflux.                             During test, patient




                                                                                                                                               Esophageal reflux study
Esophageal      pneumonia.                           More sensitive for      Abdominal binder—used to increase          must be able to con-
 reflux study                                          reflux than fluoros-      pressure in the lower esophagus—may       sume 300 mL of
 (radio-                                              copy, endoscopy, and not be tolerated in patients who have        liquid.
 nuclide)                                             manometry; sensitiv- undergone recent abdominal surgery.
                                                      ity similar to that of Contraindications and risks: Contra-
$$                                                    acid reflux test.        indicated in pregnancy because of the
                                                     Permits quantitation of potential harm of ionizing radiation to
                                                      reflux.                  the fetus.
                                                     Can also identify aspi-
                                                      ration into the lung
                                                      fields.
GI              Evaluation of dumping syndrome,       Gives functional infor- Reporting of meaningful data requires      NPO for 4– 6 hours.




                                                                                                                                                  Gastric emptying study
                 vagotomy, gastric outlet obstruc-     mation not available    adherence to standard protocol and        During test, patient
Gastric          tion due to inflammatory or neo-       by other means.         establishment of normal values.            must be able to eat a
 emptying        plastic disease, effects of drugs,                           Contraindications and risks: Contra-        300 g meal consist-
 study           and other causes of gastroparesis                             indicated in pregnancy because of the      ing of both liquids
 (radio-         (eg, diabetes mellitus).                                      potential harm of ionizing radiation to    and solids.
 nuclide)                                                                      the fetus.

$$




                                                                                                                                                                           GASTROINTESTINAL

                                                                                                                                                                                              Diagnostic Imaging: Test Selection and Interpretation
GI              Evaluation of upper or lower          Noninvasive compared Bleeding must be active during time of        Sterile technique
                 gastrointestinal blood loss.          with angiography.      imaging.                                    required during in
GI bleeding                                           Longer period of       Presence of free TcO4 (poor labeling         vitro labeling of red
 scan                                                  imaging possible,      efficiency) can lead to gastric, kidney,     cells.
 (labeled red                                          which aids in detec-   and bladder activity that can be mis-
 cell scan,                                            tion of intermittent   interpreted as sites of bleeding. Uptake




                                                                                                                                                  GI bleeding scan
 radio-                                                bleeding.              in hepatic hemangioma, varices, arteri-
 nuclide)                                             Labeled red cells and   ovenous malformation, abdominal
                                                       sulfur colloid can     aortic aneurysm, and bowel wall in-
$$–$$$                                                 detect bleeding rates  flammation can also lead to false-
                                                       as low as 0.05–        positive examination.
                                                       0.10 mL/min (angi- Contraindications and risks: Contra-
                                                       ography requires rate indicated in pregnancy because of the
                                                       of about 0.5 mL/min). potential harm of ionizing radiation to
                                                      Ninety percent sensi-   the fetus.
                                                       tivity for blood loss
                                                       > 500 mL/24 h.




                                                                                                                                                                                              265
                                                                                                                                                                             266
    Test               Indications                     Advantages              Disadvantages/Contraindications                Preparation
GALL-      Demonstrates cholelithiasis (95%       Noninvasive.              Technique very operator-dependent.           Preferably NPO for
 BLADDER sensitive), gallbladder wall thick-      No ionizing radiation.    Presence of barium obscures sound             6 hours to enhance




                                                                                                                                                                             Pocket Guide to Diagnostic Tests
            ening, pericholecystic fluid, intra-   Can be portable.           waves.                                       visualization of




                                                                                                                                                  Ultrasound
Ultrasound  and extrahepatic biliary dilation.    Imaging in all planes.    Difficult in obese patients.                   gallbladder.
 (US)                                             Can guide fine-needle      Contraindications and risks: None.
                                                   aspiration, percuta-
$                                                  neous transhepatic
                                                   cholangiography,
                                                   and biliary drainage
                                                   procedures.
GALL-      Evaluation of suspected acute          Ninety-five percent        Does not demonstrate the cause of            NPO for at least




                                                                                                                                                               GALLBLADDER
 BLADDER cholecystitis or common bile              sensitivity and 99%       obstruction (eg, tumor or gallstone).        4 hours but prefer-
            duct obstruction.                      specificity for diag-     Not able to evaluate biliary excretion if     ably less than
Hepatic    Evaluation of bile leaks, biliary       nosis of acute            hepatocellular function is severely          24 hours.
 imino-     atresia, and biliary enteric           cholecystitis.            impaired.                                   Premedication with
 diacetic   bypass patency.                       Hepatobiliary function    Sensitivity may be lower in acalculous        cholecystokinin
 acid scan                                         assessed. Defines          cholecystitis. False-positive results can    (CCK) can prevent




                                                                                                                                                  HIDA scan
 (HIDA)                                            pathophysiology           occur with hyperalimentation, pro-           false-positive exami-
                                                   underlying acute          longed fasting, and acute pancreatitis.      nation in patients
$$                                                 cholecystitis.           Contraindications and risks: Contra-          who are receiving
                                                  Rapid.                     indicated in pregnancy because of the        hyperalimentation or
                                                  Can be performed in        potential harm of ionizing radiation to      who have been fast-
                                                   patients with elevated    the fetus.                                   ing longer than
                                                   serum bilirubin.                                                       24 hours.
                                                  No intravenous con-                                                    Avoid administration
                                                   trast used.                                                            of morphine prior to
                                                                                                                          examination if
                                                                                                                          possible.
PANCREAS/ Primary sclerosing cholangitis,              Avoids surgery.           Requires endoscopy. May cause pancre-         NPO for 6 hours.
 BILIARY     AIDS-associated cholangitis, and          Less invasive than         atitis (1%), cholangitis (<1%), peritoni-    Sedation required.
 TREE        cholangiocarcinomas.                        percutaneous trans-      tis, hemorrhage (if sphincterotomy           Vital signs should be
            Demonstrates cause, location, and            hepatic cholangio-       performed), and death (rare).                 monitored by the




                                                                                                                                                                      PANCREAS/BILIARY TREE
Endoscopic   extent of extrahepatic biliary              graphy.                 Contraindications and risks: Relatively        nursing staff.
 retrograde  obstruction (eg, choledocho-              If stone is suspected,     contraindicated in patients with concur-     Not possible in patient
 cholangio-  lithiasis).                                 ERCP offers thera-       rent or recent (<6 weeks) acute pancre-       who has undergone
 pancrea-   Can diagnose chronic pancreatitis.           peutic potential         atitis or suspected pancreatic pseudocyst.    Roux-en-Y hepat-
 tography                                                (sphincterotomy and Contraindicated in pregnancy because of            icojejunostomy.




                                                                                                                                                         ERCP



                                                                                                                                                                                              Diagnostic Imaging: Test Selection and Interpretation
 (ERCP)                                                  extraction of com-       the potential harm of ionizing radiation
                                                         mon bile duct stone). to the fetus.
$$                                                     Finds gallstones in up
                                                         to 14% of patients
                                                         with symptoms but
                                                         negative ultrasound.
                                                       Plastic or metallic stent
                                                         placement may be
                                                         possible in patients
                                                         with obstruction.
LIVER         Differentiation of cystic versus solid   Noninvasive.             Technique very operator-dependent.             Preferably NPO for
               intrahepatic lesions.                   No radiation.            Presence of barium obscures sound               6 hours.
Ultrasound    Evaluation of intra- and extra-          Can be portable.          waves.




                                                                                                                                                         Ultrasound
 (US)          hepatic biliary dilation, primary       Imaging in all planes.   More difficult in obese patients.




                                                                                                                                                                      LIVER
               and metastatic liver tumors, and        Can guide fine-needle     The presence of fatty liver or cirrhosis
$              ascites.                                 aspiration, percuta-     can limit the sensitivity of ultrasound
              Evaluation of patency of portal vein,     neous transhepatic       for focal mass lesions.
               hepatic arteries, and hepatic veins.     cholangiography,        Contraindications and risks: None.
                                                        and biliary drainage
                                                        procedures.




                                                                                                                                                                                              267
                                                                                                                                                           268
   Test                  Indications                  Advantages            Disadvantages/Contraindications             Preparation
LIVER       Suspected metastatic or primary      Excellent spatial       Requires iodinated contrast material      NPO for 4– 6 hours.
             tumor, gallbladder carcinoma,        resolution.             administered intravenously.              Recent creatinine




                                                                                                                                                           Pocket Guide to Diagnostic Tests
Computed     biliary obstruction, abscess.       Can direct percuta-     Contraindications and risks: Contra-       determination.
 tomogra-                                         neous fine-needle        indicated in pregnancy because of the    Administration of oral
 phy (CT)                                         aspiration biopsy.      potential harm of ionizing radiation to   contrast material for
                                                                          the fetus. See Risks of Intravenous Con- opacification of stom-




                                                                                                                                            CT
$$$–$$$$                                                                  trast Studies, page 244.                  ach and small bowel.
                                                                                                                   Specific hepatic pro-
                                                                                                                    tocol with arterial,
                                                                                                                    portal venous, and
                                                                                                                    delayed images used
                                                                                                                    for evaluation of




                                                                                                                                                   LIVER
                                                                                                                    neoplasm.
LIVER       Assessment of number, location,        Sensitive to number of Invasive, requiring percutaneous catheter NPO for 4– 6 hours.
             and resectability of metastatic liver liver lesions (good      placement in the superior mesenteric     Recent creatinine
Computed     tumors.                                for lesion detection). artery.                                    determination.
 tomo-                                             Provides cross-         Patient must remain supine with leg       Requires some con-
 graphic                                            sectional imaging for extended for 6 hours following the pro- scious sedation.




                                                                                                                                            CTAP
 arterial                                           segmental localiza-     cedure to protect the common femoral
 porto-                                             tion of liver tumors.   artery at the catheter entry site.
 graphy                                                                    Useful for lesion detection but does not
 (CTAP)                                                                     permit characterization of lesions.
                                                                           May not be possible in patients with cir-
$$$$                                                                        rhosis where portal hypertension limits
                                                                            delivery of contrast material to liver.
LIVER        Characterization of focal hepatic   Requires no iodinated Subject to motion artifacts, particularly     Screening CT or plain
              lesion, including suspected cyst,   contrast material.      those of respiration.                       radiograph images of
Magnetic      hepatocellular carcinoma, focal    Provides excellent tis- Special instrumentation required for         orbits if history sug-
 resonance    nodular hyperplasia, and            sue contrast resolu-    patients on life support.                   gests possible metal-
 imaging      metastasis.                         tion, multiplanar      Contraindications and risks: Contra-         lic foreign body in
 (MRI)       Suspected metastatic or primary      capability.             indicated in patients with cardiac pace-    the eye.




                                                                                                                                                      LIVER
                                                                                                                                                MRI
              tumor.                                                      makers, intraocular metallic foreign       Intramuscular gluca-
$$$$         Differentiation of benign cavernous                          bodies, intracranial aneurysm clips,        gon is used to inhibit
              hemangioma from malignant                                   cochlear implants, some artificial           intestinal peristalsis.




                                                                                                                                                              Diagnostic Imaging: Test Selection and Interpretation
              tumor.                                                      heart valves.
             Evaluation of hemochromatosis,
              hemosiderosis, fatty liver, and
              suspected focal fatty infiltration.




                                                                                                                                                              269
                                                                                                                                                         270
    Test                   Indications                   Advantages          Disadvantages/Contraindications             Preparation
LIVER/        Evaluation of biliary obstruction in Best examination to    Invasive; requires special training.      NPO for 4– 6 hours.
 BILIARY       patients in whom ERCP has failed assess site and mor- Performed with conscious sedation.             Sterile technique,




                                                                                                                                                         Pocket Guide to Diagnostic Tests
 TREE          or patients with Roux-en-Y hepat- phology of obstruc-      Ascites may present a contraindication.    assessment of clot-
               icojejunostomy.                      tion close to the                                                ting parameters,
Percuta-                                            hilum (as opposed to                                             correction of
 neous trans-                                       endoscopic retrograde                                            coagulopathy.
 hepatic                                            cholangiopancreato-                                             Performed with con-
 cholangio-                                         graphy [ERCP],                                                   scious sedation.
 gram (PTC)                                         which is better for
                                                    distal obstruction).
$$$                                                Can characterize the




                                                                                                                                                 LIVER
                                                                                                                                           PTC
                                                    nature of diffuse
                                                    intrahepatic biliary
                                                    disease such as pri-
                                                    mary sclerosing
                                                    cholangitis.
                                                   Provides guidance and
                                                    access for percuta-
                                                    neous transhepatic
                                                    biliary drainage
                                                    (PTBD) and possible
                                                    stent placement to
                                                    treat obstruction.
LIVER          Preoperative evaluation for liver    Best assessment of      Invasive.                                     NPO for 4– 6 hours.
                transplantation, vascular malfor-    hepatic arterial       Patient must remain supine with leg           Good hydration to
Hepatic         mations, trauma, Budd-Chiari syn- anatomy, which is          extended for 6 hours following the pro-       limit possible renal
 angio-         drome, portal vein patency (when     highly variable.        cedure in order to protect the common         insult due to iodina-
 graphy         ultrasound equivocal) prior to      More accurate than       femoral artery at the catheter entry site.    ted contrast material.




                                                                                                                                                    Hepatic angiography
                transjugular intrahepatic portosys- ultrasound with re-     Contraindications and risks: Allergy to       Recent serum creati-
$$$$            temic shunt (TIPS) procedure.        spect to portal vein    iodinated contrast material may require       nine determination,
               In some cases, evaluation of hepatic patency when the         corticosteroid and H1 blocker or H2           assessment of clot-




                                                                                                                                                                          LIVER
                neoplasm or transcatheter embolo- latter suggests            blocker premedication. Contraindicated        ting parameters,
                therapy of hepatic malignancy.       occlusion.              in pregnancy because of the potential         reversal of anti-




                                                                                                                                                                                         Diagnostic Imaging: Test Selection and Interpretation
                                                                             harm of ionizing radiation to the fetus.      coagulation.
                                                                             Contrast nephrotoxicity may occur,           Performed with con-
                                                                             especially with preexisting impaired          scious sedation.
                                                                             renal function due to diabetes mellitus      Requires cardiac, res-
                                                                             or multiple myeloma; however, any cre-        piratory, blood pres-
                                                                             atinine elevation following the proce-        sure, and pulse
                                                                             dure is usually reversible.                   oximetry monitoring.
LIVER,        Identification of functioning splenic May detect isodense     Diminished sensitivity for small lesions       None.
 SPLEEN        tissue to localize an accessory       lesions missed by CT. (less than 1.5–2 cm) and deep lesions.
               spleen or evaluate suspected func-                           Single photon emission computed
Liver, spleen tional asplenia.                                              tomography (SPECT) increases sensi-




                                                                                                                                                                          LIVER/SPLEEN
                                                                                                                                                    Liver, spleen scan
 scan (radio- Assessment of size, shape, and posi-                          tivity (can detect lesions of 1–1.5 cm).
 nuclide)      tion of liver and spleen.                                   Nonspecific; unable to distinguish solid
              Characterization of a focal liver mass                        versus cystic or inflammatory versus
$$             with regard to inherent functioning                          neoplastic tissue. Lower sensitivity for
               reticuloendothelial cell activity                            diffuse hepatic tumors.
               (with the exception of focal nodular                        Contraindications and risks: Caution
               hyperplasia mass lesions, which are                          in pregnancy advised because of the
               more often “cold” than “hot”).                               risk of ionizing radiation to the fetus.
              Confirmation of patency and distrib-
               ution of hepatic arterial perfusion




                                                                                                                                                                                         271
               catheters.
                                                                                                                                                                       272
    Test              Indications                    Advantages             Disadvantages/Contraindications               Preparation
PANCREAS Evaluation of biliary obstruction      Can guide fine-needle Optimal imaging requires special protocol,      Preferably NPO for
           and possible adenocarcinoma.          biopsy or placement      including precontrast plus arterial and     4 – 6 hours.




                                                                                                                                                                       Pocket Guide to Diagnostic Tests
Computed  Staging of pancreatic carcinoma.       of a drainage catheter. venous phase contrast-enhanced images.      Normal hydration.
 tomogra- Diagnosis and staging of acute        Can identify early       Contraindications and risks: Contra-        Opacification of
 phy (CT)  pancreatitis.                         necrosis in              indicated in pregnancy because of the       gastrointestinal tract




                                                                                                                                               CT
                                                 pancreatitis.            potential harm of ionizing radiation to     with Gastrografin.
$$$–$$$$                                                                  the fetus. See Risks of Intravenous        Sedation of agitated




                                                                                                                                                            PANCREAS
                                                                          Contrast Studies, page 244.                 patients.
                                                                                                                     Recent serum creati-
                                                                                                                      nine determination.
PANCREAS Identification of peripancreatic fluid   Noninvasive.             Pancreas may be obscured by overlying Preferably NPO for
           collections, pseudocysts, and        No radiation.             bowel gas.                              6 hours.




                                                                                                                                               Ultrasound
Ultrasound pancreatic ductal dilation.          Can be portable.         Technique very operator-dependent.
 (US)                                           Imaging in all planes.   Presence of barium obscures sound waves.
                                                Can guide fine-needle     Less sensitive than CT.
$                                                aspiration or place-    Contraindications and risks: None.
                                                 ment of drainage
                                                 catheter.
ADRENAL      Suspected pheochromocytoma when Test is useful for          High radiation dose to adrenal gland.       Administration of
              CT is negative or equivocal.       localization of         High cost and limited availability of        Lugol’s iodine solu-
MIBG         Also useful in evaluation of neuro- pheochromocytomas        MIBG.                                       tion (to block thyroid
 (meta-       blastoma, carcinoid, and medullary (particularly extra-    Delayed imaging (at 1, 2, and 3 days)        uptake) prior to and




                                                                                                                                                            ADRENAL
                                                                                                                                               MIBG scan
 iodobenzyl- carcinoma of thyroid.               adrenal). Eighty to      necessitates return of patient.             following adminis-
 guanidine)                                      90 percent sensitive    Contraindications and risks: Contra-         tration of MIBG.
 (radio-                                         for detection of         indicated in pregnancy because of the
 nuclide)                                        pheochromocytoma.        risk of ionizing radiation to the fetus.
                                                                          Because of the relatively high dose
$$$$                                                                      of 131I, patients should be instructed
                                                                          about precautionary measures by
                                                                          nuclear medicine personnel.
GENITO-     Fluoroscopic evaluation of uro-    Permits evaluation of Suboptimal evaluation of the renal                  Adequate hydration.
 URINARY     epithelial neoplasm, calculus,     collecting system in  parenchyma.                                        Colonic cleansing is
             papillary necrosis, and medullary  less invasive manner Does not adequately evaluate cause of                preferred but not
Intravenous sponge kidney.                      than retrograde       ureteral deviation.                                 essential.




                                                                                                                                                   IVP
 pyelogram Screening for urinary system injury pyelogram.            Contraindications and risks: Caution                Recent serum creati-
 (IVP)       after trauma.                     Can assess both renal  in pregnancy is advised because of the              nine determination.
                                                morphology and        risk of ionizing radiation to the fetus.
$$$                                             function.             See Risks of Intravenous Contrast
                                                                      Studies, page 244.




                                                                                                                                                                                Diagnostic Imaging: Test Selection and Interpretation
GENITO-       Evaluation of renal morphology,          Noninvasive.           Technique very operator-dependent.         Preferably NPO for
 URINARY       hydronephrosis, size of prostate,       No radiation.          More difficult in obese patients.            6 hours.




                                                                                                                                                                GENITOURINARY
                                                                                                                                                   Ultrasound
               and residual urine volume.              Can be portable.       Contraindications and risks: None.         Full urinary bladder
Ultrasound    Differentiation of cystic versus solid   Imaging in all planes.                                             required for pelvic
 (US)          renal lesions.                          Can guide fine-needle                                               studies.
                                                        aspiration or place-
$$                                                      ment of drainage
                                                        catheter.
GENITO-       Staging of cancers of the uterus,  Provides excellent tis-     Subject to motion artifacts.                Sedation of agitated
 URINARY       cervix, and prostate.              sue contrast resolu-       Gastrointestinal opacification not yet        patients.
              Can provide information additional  tion, multiplanar           readily available.                         Screening CT or plain
Magnetic       to what is obtained by CT in some capability.                 Special instrumentation required for         radiograph images of
 resonance     cases of cancer of the kidney and No beam-hardening            patients on life support.                   orbits if history sug-




                                                                                                                                                   MRI
 imaging       urinary bladder.                   artifacts such as can      Contraindications and risks: Contra-         gests possible metal-
 (MRI)                                            be seen with CT.            indicated in patients with cardiac pace-    lic foreign body in
                                                 No ionizing radiation.       makers, intraocular metallic foreign        the eye.
$$$$                                                                          bodies, intracranial aneurysm clips,
                                                                              cochlear implants, and some artificial
                                                                              heart valves.




                                                                                                                                                                                273
                                                                                                                                                                                    274
   Test                   Indications                   Advantages              Disadvantages/Contraindications             Preparation
GENITO-      Evaluation of suspected renal         Provides functional       Finding of poor renal blood flow does      Normal hydration
 URINARY      vascular hypertension.                information without       not pinpoint an etiologic diagnosis.      needed for evalua-




                                                                                                                                                                                    Pocket Guide to Diagnostic Tests
             Differentiation of a dilated but non- risk of iodinated con-    Limited utility when renal function is     tion of suspected
Renal scan    obstructed system from one that       trast used in IVP.        extremely poor.                           obstructive uropathy
 (radio-      has a urodynamically significant      Provides quantitative     Estimation of glomerular filtration rate    since dehydration
 nuclide)     obstruction.                          information not avail-    and renal plasma flow often is             may result in false-
             Evaluation of renal blood flow and      able by other means.      inaccurate.                               positive examination.
$$            function in acute or chronic renal                             Contraindications and risks: Caution      Blood pressure should
              failure.                                                        in pregnancy because of the risk of       be monitored and an




                                                                                                                                                                    GENITOURINARY
             Evaluation of both medical and                                   ionizing radiation to the fetus.          intravenous line




                                                                                                                                                Radionuclide scan
              surgical complications of renal                                                                           started when an
              transplant.                                                                                               angiotensin-
             Estimation of glomerular filtration                                                                         converting enzyme
              rate (GFR) and effective renal                                                                            (ACE) inhibitor is
              plasma flow (ERPF).                                                                                        used to enhance test
             Determination of relative renal                                                                            sensitivity in the
              function prior to nephrectomy.                                                                            evaluation of
                                                                                                                        renal vascular
                                                                                                                        hypertension.
                                                                                                                       Patient should dis-
                                                                                                                        continue ACE
                                                                                                                        inhibitor medication
                                                                                                                        for at least 48 hours
                                                                                                                        prior to examination
                                                                                                                        if possible.
PELVIS       Evaluation of palpable ovarian mass, Use of a vaginal probe Transabdominal scan has limited sensi-        Distended bladder
              enlarged uterus, vaginal bleeding,   enables very early       tivity for uterine or ovarian pathology.    required (only in




                                                                                                                                                  Ultrasound
Ultrasound    pelvic pain, possible ectopic preg-  detection of intra-     Vaginal probe has limited field of view       transabdominal
 (US)         nancy, and infertility.              uterine pregnancy        and therefore may miss large masses         examination).
             Monitoring of follicular develop-     and ectopic preg-        outside the pelvis.
$$            ment.                                nancy and does not      Contraindications and risks: None.
             Localization of intrauterine device.  require a full bladder.
PELVIS       Evaluation of gynecologic malig-     Provides excellent tis- Subject to motion artifacts.                 Intramuscular gluca-
              nancies, particularly endometrial,   sue contrast resolu- Special instrumentation required for            gon is used to inhibit




                                                                                                                                                                        Diagnostic Imaging: Test Selection and Interpretation
Magnetic      cervical, and vaginal carcinoma.     tion, multiplanar       patients on life support.                    intestinal peristalsis.




                                                                                                                                                               PELVIS
 resonance   Evaluation of prostate, bladder, and capability.             Contraindications and risks: Contra-         Sedation of agitated
 imaging      rectal carcinoma.                   No beam-hardening        indicated in patients with cardiac pace-     patients.
 (MRI)       Evaluation of congenital anomalies    artifacts such as can   makers, intraocular metallic foreign        Screening CT or plain
              of the genitourinary tract.          be seen with CT.        bodies, intracranial aneurysm clips,         radiograph images of




                                                                                                                                                  MRI
$$$$         Useful in distinguishing lymph-      No ionizing radiation. cochlear implants, and some artificial          orbits if history sug-
              adenopathy from vasculature.                                 heart valves.                                gests possible metal-
                                                                                                                        lic foreign body in
                                                                                                                        the eye.
                                                                                                                       An endorectal device
                                                                                                                        (radiofrequency coil)
                                                                                                                        is used for prostate
                                                                                                                        MRI.




                                                                                                                                                                        275
                                                                                                                                                                 276
   Test                  Indications                   Advantages             Disadvantages/Contraindications              Preparation
BONE        Evaluation of primary or metastatic Can examine entire         Nonspecific. Correlation with plain film Patient should be well
             neoplasm, osteomyelitis, arthritis,   osseous skeleton or      radiographs often necessary.               hydrated and void




                                                                                                                                                                 Pocket Guide to Diagnostic Tests
Bone scan,   metabolic disorders, trauma, avas- specific area of            Limited utility in patients with poor renal frequently after the
 whole body cular necrosis, joint prosthesis, and interest.                 function.                                  procedure.
 (radio-     reflex sympathetic dystrophy.         Highly sensitive com-    Poor resolution in distal extremities,
 nuclide)   Evaluation of clinically suspected     pared with plain film     head, and spine; in these instances, sin-
             but radiographically occult frac-     radiography for          gle photon emission computed tomog-
$$–$$$       tures. Identification of stress        detection of bone        raphy (SPECT) is often useful.
             fractures.                            neoplasm.               Sometimes difficult to distinguish osteo-
                                                  In osteomyelitis, bone    myelitis from cellulitis or septic joint;




                                                                                                                                              Bone scan
                                                   scan may be positive     dual imaging with gallium or with




                                                                                                                                                          BONE
                                                   much earlier             indium-labeled leukocytes can be
                                                   (24 hours) than plain    helpful.
                                                   film (10–14 days).       False-negative results for osteomyelitis
                                                                            can occur following antibiotic therapy
                                                                            and within the first 24 hours after
                                                                            trauma.
                                                                           In avascular necrosis, bone scan may be
                                                                            “hot,” “cold,” or normal, depending on
                                                                            the stage.
                                                                           Contraindications and risks: Caution
                                                                            in pregnancy because of the risk of
                                                                            ionizing radiation to the fetus.
SPINE        Evaluation of structures that are not Rapid.                  Generally limited to transaxial views.   Normal hydration.
              well visualized on MRI, including Superb spatial              Coronal and sagittal reformation images Sedation of agitated
Computed      ossification of the posterior longi-   resolution.             can be generated.                        patients.
 tomogra-     tudinal ligament, tumoral calci-     Can guide percuta-      MRI unequivocally superior in evalua-
 phy (CT)     fication, osteophytic spurring,        neous fine-needle        tion of the spine and cord except for
              retropulsed bone fragments after      aspiration of possible conditions mentioned in Indications.




                                                                                                                                               CT
$$$           trauma.                               tumor or abscess.      Artifacts from metal prostheses degrade
             Also used for patients in whom                                 images.
              MRI is contraindicated.                                      Contraindications and risks: Contra-




                                                                                                                                                             Diagnostic Imaging: Test Selection and Interpretation
                                                                            indicated in pregnancy because of the
                                                                            potential harm of ionizing radiation to
                                                                            the fetus. See Risks of Intravenous
                                                                            Contrast Studies, page 244.




                                                                                                                                                     SPINE
SPINE        Diseases involving the spine and cord Provides excellent tis- Less useful in detection of calcification, Sedation of agitated
              except where CT is superior (ossifi- sue contrast resolu-      small spinal vascular malformations,      patients.
Magnetic      cation of the posterior longitudinal  tion, multiplanar       acute spinal trauma (because of longer Screening CT or plain
 resonance    ligament, tumoral calcification,       capability.             acquisition time, incompatibility with    radiograph images of
 imaging      osteophytic spurring, retropulsed    No beam-hardening        life support devices, and inferior detec- orbits if history sug-
 (MRI)        bone fragments after trauma).         artifacts such as can   tion of bony injury).                     gests possible metal-
                                                    be seen with CT.       Subject to motion artifacts.               lic foreign body in




                                                                                                                                               MRI
$$$$                                               No ionizing radiation. Special instrumentation required for        the eye.
                                                                            patients on life support.
                                                                           Contraindications and risks: Contra-
                                                                            indicated in patients with cardiac pace-
                                                                            makers, intraocular metallic foreign
                                                                            bodies, intracranial aneurysm clips,
                                                                            cochlear implants, and some artificial
                                                                            heart valves.




                                                                                                                                                             277
                                                                                                                                                                                   278
    Test                Indications                   Advantages                   Disadvantages/Contraindications              Preparation
MUSCULO- Evaluation of joints except where a Provides excellent tis-            Subject to motion artifacts.              Sedation of agitated




                                                                                                                                                                 MUSCULOSKELETAL
 SKELETAL prosthesis is in place.                sue contrast resolu-           Less able than CT to detect calcification, patients.




                                                                                                                                                                                   Pocket Guide to Diagnostic Tests
 SYSTEM    Extent of primary or malignant        tion, multiplanar               ossification, and periosteal reaction.    Screening CT or plain
            tumor (bone and soft tissue).        capability.                    Special instrumentation required for       radiograph images of
Magnetic   Evaluation of aseptic necrosis, bone No beam-hardening                patients on life support.                 orbits if history sug-




                                                                                                                                                    MRI
 resonance  and soft tissue infections, marrow   artifacts such as can          Contraindications and risks: Contra-       gests possible metal-
 imaging    space disease, and traumatic         be seen with CT.                indicated in patients with cardiac pace-  lic foreign body in
 (MRI)      derangements.                       No ionizing radiation.           makers, intraocular metallic foreign      the eye.
                                                                                 bodies, intracranial aneurysm clips,
$$$$                                                                             cochlear implants, and some artificial
                                                                                 heart valves.
VASCU-        Evaluation of deep venous thrombo-       Noninvasive.             Technique operator-dependent.              None.
 LATURE        sis, extremity grafts, patency of       No radiation.            Ultrasound not sensitive to detection of
               inferior vena cava, portal vein, and    Can be portable.          ulcerated plaque.




                                                                                                                                                                 VASCULATURE
Ultrasound     hepatic veins.                          Imaging in all planes.   May be difficult to diagnose tight steno-




                                                                                                                                                    Ultrasound
 (US)         Carotid doppler indicated for symp-                                sis versus occlusion (catheter angi-
               tomatic carotid bruit, atypical tran-                             ography may be necessary).
$$             sient ischemic attack, monitoring                                May be difficult to distinguish acute
               after endarterectomy, and baseline                                from chronic deep venous thrombosis.
               prior to major vascular surgery.                                 Contraindications and risks: None.
              Surveillance of transjugular intra-
               hepatic portosystemic shunt
               (TIPS) patency and flow.
AORTA       Peripheral vascular disease, abdom- Can localize athero-      Invasive.                                 NPO for 4– 6 hours.
 AND ITS     inal aortic aneurysm, renal artery   sclerotic stenosis and Patient must remain supine with leg        Good hydration to
 BRANCHES stenosis (atherosclerotic and fibro- assess the severity by extended for 6 hours following the pro- limit possible renal
             muscular disease), polyarteritis     morphology, flow,         cedure in order to protect the common     insult due to iodi-
Angiography nodosa, visceral ischemia, thoracic and pressure gradient. femoral artery at the catheter entry site. nated contrast
             aortic dissection, gastrointestinal Provides assessment of Contraindications and risks: Allergy to material.
$$$          hemorrhage, thromboangiitis          stenotic lesions and     iodinated contrast material may require Recent serum creati-
             obliterans (Buerger’s disease),      access for percuta-      corticosteroid and H1 blocker or H2       nine determination,
             popliteal entrapment syndrome,       neous transluminal       blocker premedication. Contraindicated assessment of clot-




                                                                                                                                                                     Diagnostic Imaging: Test Selection and Interpretation
             cystic adventitial disease, abdomi- balloon dilation as       in pregnancy because of the potential     ting parameters,




                                                                                                                                               Angiography
             nal tumors, arteriovenous malfor-    well as stent treat-     harm of ionizing radiation to the fetus.  reversal of anti-




                                                                                                                                                             AORTA
             mations, abdominal trauma.           ment of iliac stenoses. Contrast nephrotoxicity may occur,         coagulation.
            Preoperative evaluation for aorto- Provides access for         especially with preexisting impaired     Performed with con-
             femoral bypass reconstructive        thrombolytic therapy renal function due to diabetes mellitus       scious sedation.
             surgery.                             of acute or subacute     or multiple myeloma; however, any cre- Requires cardiac, res-
            Postoperative assessment of possi-    occlusion of native      atinine elevation that occurs after the   piratory, blood pres-
             ble graft stenosis, especially       artery or bypass         procedure is usually reversible.          sure, and pulse
             femoral to popliteal or femoral to   graft.                                                             oximetry monitoring
             distal (foot or ankle).                                                                                 as well as non-
                                                                                                                     invasive studies of
                                                                                                                     peripheral vascular
                                                                                                                     disease to verify indi-
                                                                                                                     cation for angio-
                                                                                                                     graphy and to guide
                                                                                                                     the examination.




                                                                                                                                                                     279
                                                                                                                                                             280
    Test               Indications                     Advantages           Disadvantages/Contraindications                Preparation
AORTA      Can provide preoperative assess-       No ionizing radiation. Subject to motion artifacts.                Sedation of agitated
 AND ITS    ment of abdominal aortic aneu-        No iodinated contrast Special instrumentation required for          patients.




                                                                                                                                                             Pocket Guide to Diagnostic Tests
 BRANCHES rysm to determine aneurysm size,         needed.                patients on life support.                  Screening CT or plain
            proximal and distal extent, rela-                            Contraindications and risks: Contra-         radiograph images of




                                                                                                                                                     AORTA
                                                                                                                                               MRA
Magnetic    tionship to renal arteries, and pres-                         indicated in patients with cardiac pace-    orbits if history sug-
 resonance  ence of anatomic anomalies.                                   makers, intraocular metallic foreign        gests possible metal-
 angiogra- Permits evaluation of the hemo-                                bodies, intracranial aneurysm clips,        lic foreign body in
 phy (MRA) dynamic and functional signifi-                                 cochlear implants, and some artificial       the eye.
            cance of renal artery stenosis.                               heart valves.
$$$$
BLOOD          Evaluation of fever of unknown ori- Highly specific (98%)      24-hour delayed imaging may limit the       Leukocytes from the
                gin, suspected abscess, pyelone-    for infection (in con-    utility of indium scan in critically ill    patient are harvested,
Leukocyte       phritis, osteomyelitis, and         trast to gallium).        patients.                                   labeled in vitro, and
 scan           inflammatory bowel disease.         Highly sensitive in       False-negative scans occur with anti-        then reinjected;
 (indium       Examination of choice for evalua-    detecting abdominal       biotic administration or in chronic         process requires
 scan, labeled tion of suspected vascular graft     source of infection.      infection.                                  12 hours. Scanning
 white blood infection.                            In patients with fever    Perihepatic or splenic infection can be      takes place 24 hours
 cell [WBC]                                         of unknown origin,        missed because of normal leukocyte          after injection of
 scan,                                              total body imaging is     accumulation in these organs; liver and     indium-labeled




                                                                                                                                                                         Diagnostic Imaging: Test Selection and Interpretation
 technetium-                                        advantageous com-         spleen scan is necessary adjunct in this    WBC and 1–2 hours
 99m hexa-                                          pared with CT scan        situation.                                  after injection of
 methylpro-                                         or ultrasound.           False-positive scans occur with swal-        Tc99m-HMPAO
 pyleneamine                                       Preliminary imaging as     lowed leukocytes, bleeding, indwelling      WBC.




                                                                                                                                                   Indium scan
 oxime                                              early as 4 hours is       tubes and catheters, surgical skin wound Homologous donor




                                                                                                                                                                 BLOOD
 [Tc99m-                                            possible with indium      uptake, and bowel activity due to           leukocytes should be
 HMPAO]-                                            but less sensitive        inflammatory processes.                      used in neutropenic
 labeled                                            (30–50% of abscesses     Pulmonary uptake is nonspecific and has patients.
 WBC scan,                                          are detected at           low predictive value for infection.
 radio-                                             24 hours).               Patients must be able to hold still during
 nuclide)                                                                     relatively long acquisition times
                                                                              (5–10 minutes).
$$–$$$                                                                       Tc99m-HMPAO WBC may be sub-
                                                                              optimal for detecting infection involving
                                                                              the genitourinary and gastrointestinal
                                                                              tracts because of normal distribution of
                                                                              the agent to these organs.
                                                                             Contraindications and risks: Contra-
                                                                              indicated in pregnancy because of the
                                                                              hazard of ionizing radiation to the fetus.
                                                                              High radiation dose to spleen.




                                                                                                                                                                         281
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                                                                                      7
                            Basic Electrocardiography*




                                                            G. Thomas Evans, Jr., MD




        HOW TO USE THIS SECTION

        This chapter includes criteria for the diagnosis of basic electrocardio-
        graphic waveforms and cardiac arrhythmias. It is intended for use as
        a reference and assumes a basic understanding of the electrocardio-
        gram (ECG).
             Electrocardiographic interpretation is a “stepwise” procedure, and
        the first steps are to study and characterize the cardiac rhythm.

        Step One
        Categorize what you see in the 12-lead ECG or rhythm strip, using the
        three major parameters that allow for systematic analysis and sub-
        sequent diagnosis of the rhythm:
             1. Mean rate of the QRS complexes (slow, normal, or fast).
             2. Width of the QRS complexes (wide or narrow).
             3. Rhythmicity of the QRS complexes (characterization of spaces
        between QRS complexes) (regular or irregular).

        * Adapted, with permission, from Evans GT Jr.: ECG Interpretation Cribsheets, 4th ed.
        Ring Mountain Press, 1999.
                                                283
Copyright 2001 The McGraw-Hill Companies. Click Here for Terms of Use.
284    Pocket Guide to Diagnostic Tests

     Based upon this categorization, refer to pages 286–299 for specific
categories of rhythms. If the rhythm is irregularly irregular, go directly
to page 288 (atrial fibrillation). For specific criteria for atrial flutter, go
to page 288.

Step Two
Step 2 consists of examining and characterizing the morphology of the
cardiac waveforms.
     1. Examine for atrial abnormalities and bundle branch blocks
(BBBs) (pages 301–302).
     2. Assess the QRS axis and the causes of axis deviations (pages
304–306).
     3. Examine for signs of left ventricular hypertrophy (pages
306–307).
     4. Examine for signs of right ventricular hypertrophy (pages
307–308).
     5. Examine for signs of myocardial infarction, if present (pages
310–320).
     6. Bear in mind conditions that may alter the ability of the ECG
to diagnose a myocardial infarction (page 320).
     7. Examine for abnormalities of the ST segment or T wave (pages
320–323).
     8. Assess the QT interval (pages 324–327).
     9. Examine for miscellaneous conditions (pages 327–330).


STEP 1: DIAGNOSIS OF THE CARDIAC RHYTHM

A. APPROACH TO DIAGNOSIS OF THE CARDIAC RHYTHM

Most electrocardiograph machines display 10 seconds of data in a stan-
dard tracing. A rhythm is defined as three or more successive P waves
or QRS complexes.
     Categorize the patterns seen in the tracing according to a sys-
tematic method. This method proceeds in three steps that lead to a
diagnosis based upon the most likely rhythm producing a particular
pattern:

  1. What is the mean rate of the QRS complexes?
     Slow (<60 bpm): The easiest way to determine this is to count
       the total number of QRS complexes in a 10-second period. If
       there are no more than 9, the rate is slow.
                                                            Basic Electrocardiography          285

TABLE 7–1. SUSTAINED REGULAR RHYTHMS.

   Rate                Fast                         Normal                       Slow

Narrow QRS   Sinus tachycardia               Sinus rhythm              Sinus bradycardia
  duration   Atrial tachycardia              Ectopic atrial rhythm     Ectopic atrial bradycardia
             Atrial flutter                   Atrial flutter
                (2 1 AV conduction)             (4 1 conduction)
Wide QRS     All rhythms listed above under narrow QRS duration, but with BBB or
  duration      intraventricular conduction delay (IVCD) patterns
             Ventricular tachycardia         Accelerated ventricular   Ventricular escape rhythm
                                               rhythm



     Normal (60–100 bpm): If there are 10–16 complexes in a
        10-second period, the rate is normal.
     Fast (> 100 bpm): If there are ≥ 17 complexes in a 10-second
        period, the rate is fast.
  2. Is the duration of the dominant QRS morphology narrow (≤ 0.119 s)
     or wide (≥ 0.12 s)? (Refer to the section below on the QRS duration.)
  3. What is the “rhythmicity” of the QRS complexes (defined as the
     spacing between QRS complexes)? Regular or irregular? (Any
     change in the spacing of the R-R intervals defines an irregular
     rhythm.)

     Using the categorization above, refer to Tables 7–1 and 7–2 to
select a specific diagnosis for the cardiac rhythm.


TABLE 7–2. SUSTAINED IRREGULAR RHYTHMS.

   Rate                  Fast                            Normal                     Slow

Narrow QRS   Atrial fibrillation                  Atrial fibrillation         Atrial fibrillation
  duration   Atrial flutter (variable             Atrial flutter (variable    Atrial flutter (variable
                AV conduction)                      AV conduction)             AV conduction)
             Multifocal atrial tachycardia       Multiform atrial rhythm    Multiform atrial rhythm
             Atrial tachycardia with             Atrial tachycardia with
                AV block (rare)                     AV block (rare)
Wide QRS     All rhythms listed above under narrow QRS duration, but with BBB or IVCD
  duration      patterns
             Rarely, anterograde conduc-
               tion of atrial fibrillation
               over an accessory
               pathway in patients with
               WPW syndrome
286   Pocket Guide to Diagnostic Tests

B. CATEGORIES OF QRS RHYTHM IRREGULARITY

A Dominant Regular Rhythm With Interruptions
This is the most common category of irregularity. Diagnoses include
the following:

  A. An atrial pause, defined as occasional abrupt pauses not initiated
     by premature QRS activity (and accompanied by a change in the
     P-P interval). Causes include: a nonconducted premature atrial
     complex (PAC) (most common); sinus pause (less common); atypi-
     cal sinus arrhythmia (less common); and sinoatrial exit block (rare).
  B. During tachycardia, occasional lengthening of the R–R cycle,
     unmasking the presence of either regular atrial activity or flutter
     waves.
  C. Premature QRS activity that initiates a pause, called a post-
     extrasystolic pause, with either (1) a narrow QRS complex (most
     common) due to either a normally conducted premature atrial
     complex (PAC) or, rarely, a premature junctional complex (PJC);
     or (2) a wide or abnormal QRS complex, due to a premature
     ventricular complex (PVC), the most common cause of a de novo
     wide QRS complex; aberrant ventricular conduction of a pre-
     mature supraventricular impulse (either a PAC or PJC); or, rarely,
     a PAC that conducts over an accessory pathway.

Aberrant Ventricular Conduction
Aberrant ventricular conduction is defined as an abnormal QRS com-
plex formed by premature activation of the His-Purkinje system that
results in block of the impulse in one of the bundle branches. Aberrant
conduction is usually a normal phenomenon and does not imply disease
of the conduction system. The PR interval of a PAC that causes aber-
rant ventricular conduction is commonly prolonged.

An Irregularly Irregular Rhythm
Irregularly irregular rhythms have successive RR intervals that occur
in random patterns. One method of ascertaining this pattern is to place
calipers on the first RR interval at the start of the tracing and to pre-
cisely adjust the calipers to each successive RR interval throughout
the 10-second period. If there are random changes in the intervals, the
rhythm is irregularly irregular.
      An irregularly irregular rhythm is usually the QRS “footprint” of
(1) atrial fibrillation (most common sustained abnormal cardiac rhythm),
(2) atrial flutter (with variable AV conduction), (3) multifocal atrial
                                                    Basic Electrocardiography           287

tachycardia (MAT), (4) atrial tachycardia with AV block, or (5) other
less common rhythms.

Regularly Irregular Rhythm (“Group Beating”)
Group beating is defined as clusters of regularly spaced QRS com-
plexes, separated by pauses of identical duration. Whenever there is
group beating, consider some form of Wenckebach periodicity, either
during AV block or during junctional tachycardia with exit block in dig-
italis toxicity. Causes of group beating include the following:

  A. Second-degree AV block, type I (Wenckebach) or type II
     (Mobitz II): There are usually single—but rarely multiple—
     nonconducted P waves in the setting of a constant PP interval.
  B. PVCs in a repetitive pattern (ventricular trigeminy, quadrigeminy).
  C. PACs or PJCs in a repetitive pattern (atrial trigeminy, etc).

Accelerating-Decelerating Rhythm
Causes include sinus arrhythmia (most common), defined as PP inter-
vals that vary by > 10%; and sinoatrial exit block in a Wenckebach pat-
tern (rare).


C. SINUS RHYTHMS

Sinus rhythms are defined by upright P waves in leads I, II, and aVF
(present in 94% of normals) and are classified in Table 7–3.


D. ATRIAL RHYTHMS

Atrial rhythms, by definition, have nonsinus P waves. Focal atrial
arrhythmias are defined as arrhythmias with a single focus (Table 7–4).

Multifocal Atrial Tachycardia (MAT)
Defined as having P waves with three or more morphologies per lead,
with variable P-R intervals, and a mean atrial rate > 100/min. There is

TABLE 7–3. SINUS RHYTHMS.

Sinus rhythm          Rate 60–100 bpm
Sinus bradycardia     Rate <60 bpm (or <55 in persons age >65)
Sinus tachycardia     Rate >100 bpm
Sinus arrhythmia      Sinus P waves with >10% variation in PP intervals (due to respiration)
288    Pocket Guide to Diagnostic Tests

           TABLE 7–4. ATRIAL RHYTHMS.

            Ectopic atrial bradycardia   Rate <60 bpm
            Ectopic atrial rhythm        Rate 60–100 bpm
            Atrial tachycardia           Rate >100 bpm, but usually <240–250 bpm



commonly nonconducted atrial activity. The baseline between T waves
and P waves is isoelectric. The cause is COPD (60% of cases).

Atrial Fibrillation
Atrial fibrillation is the most common sustained abnormal cardiac rhythm.
It is defined by the presence of fibrillatory waves that have a small ampli-
tude and very rapid rate and are characterized by an inconstancy of mor-
phology. They are best seen in leads V1, V2, II, aVF, and III.

Atrial Flutter
Classic atrial flutter, seen in two-thirds of patients, produces the wave-
forms shown below, usually at an atrial rate of 250–350/min.

  II, aVF, III                                       “Sawtooth” morphology

      V1                                             Discrete upright “P” waves



E. JUNCTIONAL RHYTHMS
“Junctional rhythm” is not recommended terminology for a final rhythm
diagnosis because the specific subtypes have clinical implications.

Definition of Junctional Complexes
There are three possible relationships between the P waves and QRS
complexes during junctional complexes or rhythms:
  A. A constant PR interval ≥0.08 s with a 1 1 AV ratio.
  B. No discernible P wave activity (P waves buried in the QRS
     complexes).
  C. A retrograde P wave following the QRS complex.

Definition of an Escape Complex or Rhythm
An escape complex or rhythm occurs when a lower down, subsidiary
(secondary) pacemaking site assumes the role of cardiac pacemaker
                                                                Basic Electrocardiography                289

TABLE 7–5. THREE TYPES OF JUNCTIONAL RHYTHM.

           Rhythm                          Rate                         Clinical Correlates

 Junctional escape rhythm           Rate <60 bpm             Sinus node dysfunction or drug side effects
 Accelerated junctional rhythm      Rate 61–100 bpm          Digitalis toxicity, post cardiac surgery,
                                                                rheumatic fever, infections of the AV
                                                                node area, idiopathic
 Junctional tachycardia             Rate >100 bpm            Same as accelerated junctional rhythm




because of failure of a primary pacer site anatomically superior to the
escape focus. Note: “Escape” always implies normal function of the
structure that is escaping and that an anatomically superior pacemaker
has failed. Escape rhythms are usually very regular.

Definition of an Accelerated Complex or Rhythm
In contrast, an accelerated rhythm always implies abnormal function of
the structure that is accelerated. The lower rate limit of accelerated
rhythms equals the upper rate limit of the escape rate of the structure
but is <101 bpm. Accelerated rhythms are usually very regular.

Classification of Junctional Rhythms
Table 7–5 summarizes a useful classification of junctional rhythms.


F. VENTRICULAR RHYTHMS

Definition of Ventricular Complexes
Ventricular complexes are not initiated by atrial activity and have a
morphology that is inconsistent with that of typical RBBB or LBBB.
The QRS duration is ≥0.12 s, usually between 0.14 s and 0.16 s. There
are three major types of ventricular rhythms (Table