SEMINARS IN THROMBOSIS AND HEMOSTASIS-VOL. 10, NO. 4, 1984
Performance Characteristics of a Simple
Radioimmunoassay for Fibrinopeptide A
JEANINE M. WALENGA, B.S., M.T.(ASCP),
DEBRA HOPPENSTEADT, B.S., M.T.(ASCP),
R. MARTIN EMANUELE, M.S., and JAWED FAREED, Ph.D., F.A.C.B.
Although the endogenous generation of fibrino- Fibrinopeptide A is a small peptide released
peptide A (FPA) has been known for many years, it from the N-terminal of the alpha chain of fibrino-
has been primarily used as a research tool rather gen. Upon the action of thrombin, two peptides
than a diagnostic measure.36,37,39,41,42 Early from the alpha chain and two peptides from the
methods for quantitation of FPA did not provide beta chain are generated as the first products of
specificity, were expensive, complicated, and time- cleavage. Table 1 illustrates this reaction. FPA
consuming. Today, there are commercially available consists of 16 amino acids with a molecular weight
FPA kits that provide reliable data by either radio- of 1535 daltons. The circulating half-life of FPA
immunoassay (RIA) or enzyme-linked immuno- is 3 to 4 minutes.1,31 The use of the earliest re-
sorbent assay (ELISA) methods. These assays are lease products from fibrinogen in a clinical setting
not difficult to perform and are less time-consum- can provide sensitivity not offered by any previous
ing than the earlier methods. Since RIA and ELISA marker of thrombosis.3,11,12 Other assays, such as
methodologies are common to clinical laboratories, the prothrombin time (PT) and partial thrombo-
FPA quantitation can be adapted to any laboratory plastin time (PTT), the measurement of fibrin(ogen)
to perform this type of testing. degradation products, and the protamine paracoag-
At present, commercial assays are available ulation or ethanol gelation tests for fibrin mono-
from: Diagnostica Stago (Asnieres, France), As- mers, are much less sensitive and specific than FPA
serachrom FPA (ELISA); IMCO (Stockholm, measurement. Well before any change is observed
Sweden), fibrinopeptide 125I assay kit (RIA); and in any of these assays, the generated FPA will show
Mallinckrodt (St. Louis, MO), RIA Quant FPA test an elevation above normal, since determinations are
kit (125I RIA). Our laboratories have evaluated all made in nanogram per milliliter amounts.
three kits and found excellent correlation among Although FPA can be used to aid in the diag-
them; however, the data presented in this article nosis of the common thrombotic problems, such as
were obtained using the Mallinckrodt 125I kit. This deep vein thrombosis and pulmonary embolism,17,
is the method routinely used because an iodination due to its high sensitivity toward detecting
step is not required before performing the assay, as thrombotic activity, it is also potentially useful in
must be done with the IMCO kit, and solid phase the diagnosis and prognosis of such disorders as
support problems are never encountered, as is the myocardial infarction, malignancies, lupus erythe-
case with the Diagnostica Stago kit. Application of matosus, and nephritis. 6,7,10,20,34-38,44-46,52 Addi-
high-performance liquid chromatography tech- tionally, burns, fractures, and surgery, which can
nology has also been done by several investi-
gators.21,25 TABLE 1. Conversion of Fibrinogen to Fibrin
From the Department of Pathology, Hemostasis Research
Laboratories, Loyola University Stritch School of Medicine,
Reprint requests: Ms. Walenga, Loyola University Medical
Center, Department of Pathology, 2160 South First Avenue,
Maywood, IL 60153.
Publisher: Thieme-Stratton Inc., 381 Park Avenue South, New York, NY 10016 219
220 SEMINARS IN THROMBOSIS AND HEMOSTASIS-VOL. 10, NO. 4, 1984
TABLE 2. Diagnostic Value of Fibrinopeptide A nite is required. Recovery studies using FPA show
no interference of the bentonite treatment on FPA
1. Hypercoagulable state
in the sample, and the data are shown in Table 3.
2. Thrombotic disease
Deep vein thrombosis This is much simpler and easier than the dialysis
Pulmonary embolism procedures recommended by earlier investigators,
3. Malignancy thus reducing turnaround time of the assay to ap-
4. Burns proximately 2 hours, depending on the number of
5. Fractures samples analyzed.31
6. Postsurgical thrombosis The test procedure is based on a competitive
7. Lupus erythematosus binding between radiolabeled FPA and unlabeled
8. Nephritis (test) FPA for a limited number of binding sites on
9. Procoagulant and anticoagulant therapy exogenously added FPA antiserum. A polyethylene
glycol second antibody solution is used to separate
the free and antibody-bound FPA. After centrifuga-
produce thrombosis, can be monitored for FPA to tion, the pellet containing the labeled FPA-antibody-
reduce serious complications.27'33 The most impor- second antibody complex is counted for radio-
tant use of FPA is in the detection of a hypercoagu- activity. This procedure is illustrated in Table 4. An
lable state before it leads to thrombus and embolus increased FPA level in the test sample will allow less
production. Table 2 summarizes the diagnostic labeled FPA to bind to the limited antibody, and
value of FPA measurement. Hopefully, such painful thus less label is precipitated into the pellet (most
invasive procedures as venographics and Doppler will be removed in the supernatant). Therefore, an
plethysmography can be replaced by the more sensi- increased FPA test level results in a lower radio-
tive FPA. The newer antithrombotic and prothrom- activity count. Standards and controls are provided
botic therapies can be readily assessed by FPA, in the kit for a standard curve against which test
because the most commonly used methods are not levels can be determined. A typical standard curve
sensitive enough to detect the action of these pro- as performed in our laboratory is shown in Figure 1.
ducts. 43,48,53 Special products for therapeutic use as
blood components or prothrombin concentrates can
be subjected to quality control prior to human con- TABLE 4. Flow Sheet for Fibrinopeptide A
Quantitation by RIA
sumption.17,50 Also, certain procedures, such as
leukophoresis, kidney dialysis, and extracorporeal Pretreat test plasma with bentonite to remove antigenically
blood circulation, can be monitored for safety to cross-reacting fibrinogen and fibrin split products
the patient by assessing the extent of blood acti-
vations.8,9 Add 125I FPA to test plasma
Add FPA antiserum
The Mallinckrodt FPA assay is an 125I labeled Incubate
RIA that provides sensitivity from 0 to 40 ng/ml. Competitive binding between the antiserum, labeled and
For specificity to the FPA without cross-reactivity nonlabeled (patient) FPA occurs
from fibrinogen, a simple pretreatment with bento-
Add second antibody
TABLE 3. Fibrinopeptide A Recovery Studies for the Centrifuge; decant
Mallinckrodt RIA Kit*
Plasma Diluent Standard Diluent Separation of the antibody-bound FPA and
nonbound FPA takes place
Expected Recovered Expected Recovered
(ng/ml) (ng/ml)† (ng/ml) (ng/ml)
30.0 30.0 27.5 27.5
24.0 24.7 22.0 22.8 Discard unbound-FPA Radiolabeled and nonlabeled
18.0 18.6 16.5 16.8 in supernatant antibody-bound FPA in pellet
12.0 12.2 11.0 11.3
6.0 6.3 5.5 6.0
3.0 2.9 2.8 2.4 Count radioactivity of pellet*
1.5 1.4 1.4 1.3
*An inverse relationship exists between the level of radioactivity
*This study was performed at the Mallinckrodt laboratories. measured and the amount of FPA in the test plasma; that is,
Dilutions were made with plasma or the 0.0 standard supplied higher concentrations of patient test FPA cause less labeled
with the kit prior to the bentonite treatment. FPA to bind to the antibody, thereby producing lower radio-
†Corrected for plasma background FPA. activity counts in the final pellet.
PERFORMANCE CHARACTERISTICS OF A RIA FOR FPA - WALENGA, ET AL 221
Reproducibility of the Mallinckrodt FPA assay
depends on carefully following the manufacturer's
instructions because of the extreme sensitivity of the
assay, which will detect any mishandling of reagents
or specimens. However, these precautions involve
common sense that should be routinely employed
by practicing laboratory personnel. Table 5 shows
data for intra-assay variability on three control
levels and two plasma levels for which the coeffi-
cient of variation ranged from 3.16 to 6.46%. The
interassay variability, shown in Table 6, ranges
from 3.78 to 11.20%.31
SAMPLE COLLECTION AND HANDLING
In order to obtain appropriate samples for FPA
determinations, it is necessary to use special collec-
tion and handling techniques and anticoagulants.
Usually, blood plasma is utilized for FPA; how-
ever, spinal fluid, urine, ascites, and other body
fluids can be used. Due to the fact that FPA is pro-
duced as the earliest marker of thrombin's action on
fibrinogen, special precautions in sample handling
are necessary in order to prevent an increase in the
FIG. 1. Standard curve for the Mallinckrodt fibrinopeptide values by mechanical or other exogenous activation.
A RIA assay. This is a typical standard curve of bound/ Harsh treatment of a blood sample, poor venipunc-
unbound label (%) versus standard concentrations of fibrinopep-
ture, improper centrifugation, time, and tempera-
ture can cause exogenous release of FPA. The
sensitivity of this assay is critical to its diagnostic
TABLE 5. Intra-Assay Variability of the Mallinckrodt Fibrinopeptide A Kit*
Lyophilized Control Plasma Normal Human Plasma
Runt I II III I II
1 (n = 21)
± SD (ng/ml) 1.37 ± 0.10 7.11 ± 0.25 24.10 ± 0.66 1.12 ± 0.07 8.70 ± 0.23
CV (%) 7.44 3.51 2.73 6.07 2.63
2(n = 21)
± SD (ng/ml) 1.41 ± 0.08 7.13 ± 0.16 24.02 ± 0 . 6 8 1.28 ± 0.06 8.89 ± 0.37
CV (%) 5.45 2.27 2.83 4.90 4.12
± SD (ng/ml) 1.35 ± 0.09 7.22 ± 0.27 23.77 ± 1.18 1.12 ± 0.07 8.55 ± 0.30
CV (%) 6.48 3.71 4.95 6.07 3.52
Composite of 3 runs (n = 63)
± SD (ng/ml) 1.38 ± 0.09 7.15 ± 0.23 23.96 ± 0.84 1.17 ± 0.07 8.71 ± 0.30
CV (%) 6.46 3.16 3.50 5.68 3.42
*This study was performed in the Mallinckrodt laboratories using three individual kit lots. The compiled data for the
three separate lots are also given.
† : mean; CV: coefficient of variability.
TABLE 6. Interassay Variability of the Mallinckrodt Fibrinopeptide A Kit*
Lyophilized Control Plasma Normal Human Plasma
Run† I II III I II
± SD (ng/ml) 1.29 ± 0.13 7.03 ± 0.31 25.44 ± 1.20 1.16 ± 0.13 8.65 ± 0.33
CV (%) 10.08 4.41 4.72 11.20 3.78
Number 189 189 189 562 562
*This study was performed at the Mallinckrodt laboratories. Three different lots were assayed.
† : mean; CV: coefficient of variability.
222 SEMINARS IN THROMBOSIS AND HEMOSTASIS-VOL. 10, NO. 4, 1984
value; however, this does present particular con-
siderations in sample handling.
Therefore, the only blood sample acceptable
for FPA quantitation is one in which there is a clean
venipuncture using a double-syringe technique to
discard the first 3 ml of blood. The collection tube
should be prechilled and the sample should be im-
mediately placed on ice after filling and centrifuged
at 4°C within 30 minutes of collection. If analysis is
not to be performed immediately, the plasma
should be frozen at -70°C. FPA quantitation by
the Mallinckrodt kit after various sample-handling FIG. 2. Fibrinopeptide levels in a normal male population.
procedures is described by Walenga et al elsewhere Plasmas were collected in a special anticoagulant and frozen
in this issue of Seminars. before assaying.
The anticoagulant is the most important factor
in obtaining a proper sample. A special anticoagu-
lant developed by Mallinckrodt contains ethylene
diaminetetraacetic acid (EDTA), aprotinin, and a
thrombin inhibitor. This provides inhibition of
coagulation by chelating calcium and by blocking
kallikrein to inhibit the contact system, if any
clotting has occurred, a thrombin inhibitor will stop
any final action on fibrinogen. Data from Loyola
Medical Center clearly illustrate the efficacy of this
anticoagulant. These data have been published else-
where in this issue of Seminars.
FIG. 3. Fibrinopeptide A levels in a normal female popula-
CLINICAL APPLICATION tion. Plasmas were collected in a special anticoagulant and
frozen before assaying.
To assess the Mallinckrodt FPA assay kit and
to define normal range values in our laboratory, showed higher values than males, 32.0 ± 6.6 µg/ml
specimen from normal human volunteers were as- as opposed to 27.1 ± 8.4 µg/ml. In addition, the
sayed. Data were categorized by male and female distribution of FPA levels seemed more concentrated
and plasma and serum. Plasma samples were col- at higher levels in females, whereas males were
lected in the previously described manner and evenly distributed. These data, as shown in Figures
frozen at -70°C for 1 week to 4 months. Figure 2 4 and 5, reflect the differences in clotting rates be-
shows a histogram for normal male FPA levels. The tween males and females.
mean is 1.5 ± 1.1 ng/ml with a fairly normal dis- Normal human plasma or serum pools, as pre-
tribution. Similarly for females (Fig. 3), the mean is pared for daily control in our laboratory using a
1.9 ± 1.2 ng/ml, slightly higher than that for double-syringe technique and sodium citrate as an
males, with a fairly normal distribution. There ap- anticoagulant, were used to evaluate the perform-
pears to be a higher frequency and narrower distri- ance characteristics of this FPA kit. Twenty aliquots
bution of the population at lower than mean values of one lot of normal plasma pool were run simul-
for both male and female groups. Above the mean taneously to assess the intra-assay variation. Simi-
there is lower frequency and wider distribution of larly, 20 aliquots of normal serum pool were simul-
population for the higher values of FPA. In other taneously run. At slightly elevated levels, due to the
words, most normal values will be from 0.1 to 1.5 anticoagulant used, the plasma gave 7.9 ± 1.8 ng/
ng/ml and less frequently from 1.5 to 5.25 ng/ml. ml and the serum gave 12.5 ± 0.7 µg/ml FPA
Values greater than 2.0 ng/ml should be evaluated levels. At very high concentrations, the variation was
for the normality of the volunteer and reanalyzed to not statistically significant; however, at low ranges,
be sure that the true normal value is that high. It is there was a higher variation. Due to the sensitivity
generally accepted that normal values range from 0 of this assay, that is, measurements in the nanogram
to 2.0 ng/ml. range, these variations are to be expected. However,
In an identical fashion, serum from males and from the data to follow, it will be clear that normal
females were analyzed. As expected, FPA levels and abnormal values are easily distinguished by a
were extremely high; however, the female group range of values generally accepted for each group,
PERFORMANCE CHARACTERISTICS OF A RIA FOR FPA - WALENGA, ET AL 223
FIG. 6. A low level FPA control supplied in the Mallinckrodt
FIG. 4. Fibrinopeptide A levels in normal serum of males.
Serum was collected in glass and frozen before use.
FIG. 7. A high level FPA control supplied in the Mal-
FIG. 5. Fibrinopeptide A levels in normal serum of females.
Serum was collected In glass and frozen before use. marker. For thrombotic diseases, such as deep vein
thrombosis in which there is ongoing coagulation
activity, FPA is an obvious choice to monitor the
if proper collection technique is followed. Table 7 disease. Evaluations were also done for cases of
illustrates these data. malignancy in which thrombotic activity is second-
To assess interassay variability, both high and ary to the initial disease. Table 8 lists data for 18
low controls supplied with the kit were included in various neoplasias and their accompanying FPA
daily runs. The low control (Fig. 6) gave a mean of levels. These plasmas were obtained from San
1.1 ± 0.3 ng/ml with a normal distribution and the Joaquin Hematology/Oncology Group in Bakers-
high control gave a mean of 7.6 ± 0.6 ng/ml with a field, California. Samples were collected as recom-
normal distribution (Fig. 7). Again at lower concen- mended and frozen prior to analysis. Half of the
trations the variation was higher than that for above samples show elevated levels. A more complete
normal concentrations, as seen in the intra-assay study should be undertaken in which a larger
data. However, this does not interfere in clinical number of samples per group at various stages of
diagnoses. The Mallinckrodt FPA kit was used in each type of malignancy are analyzed. However, in
investigations of numerous disease states to deter- this preliminary study, FPA appears to be an
mine whether FPA could be included as a diagnostic appropriate indicator of ongoing malignancy. This
analysis will also be beneficial not only in proper
TABLE 7. Comparison of Fibrinopeptide A Levels in diagnosis but also in selecting the proper therapy
Plasma and Serum in an Intra-Assay for all secondary clinical involvements. Previously
Performance Study* published articles 2,4,5,13-16,18,19,22,23,28-30,32,47,51 as
Human Plasma Human Serum well as other articles in this issue of Seminars report
on further clinical uses of FPA quantitation.
± SD (ng/ml)t 7.9 ± 1.8 12,500 ± 700
CV (%)† 22.8 5.6 Table 9 shows the results of FPA levels in 14
patients with suspected hypercoagulable state due
*Twenty individual aliquots of each sample were assayed to as-
sess the performance characteristics of the Mallinckrodt FPA
to deep vein thrombosis (OVT), low antithrombin
kit. Plasma was collected in sodium citrate. III (AT III) levels, and shortened PT and PTT.
† : mean; CV: coefficient of variation. In all of these patients the FPA levels are signifi-
224 SEMINARS IN THROMBOSIS AND HEMOSTASIS-VOL. 10, NO. 4, 1984
TABLE 8. Fibrinopeptide A Levels in Various TABLE 10. Fibrinopeptide A Level in Various
Malignancies* Disorders of Fibrinolysis*
Fibrinopeptide A Disorder FPA (ng/ml)
Malignancy No. (ng/ml ± 1 S.D.)
Primary fibrinolysis 6.1 ± 3.2
Gastric 1 10 Malignancy
Neck 1 12.5 Pregnancy
Breast 15 8.5 ± 10.7
Secondary fibrinolysis 14.1 ± 6.4
Squamous cell 2 5.2 ± 5.1
Prostatic 3 5.3 ± 3.6
Gallbladder 1 5.0 Normal 2.8 ± 0.9
Renal cell 1 4.8 *All results are expressed as means of ten individual determina-
Esthesioneuroblastoma 1 3.7 tions ± 1 SD.
Colon 6 3.2 ± 2.8
Pancreatic 3 3.1 ± 1.6
Hairy cell leukemia 1 2.6
Chronic myelocytic leukemia 1 2.4 Many investigators realize the importance and
Multiple myeloma 1 2.4 direct application of FPA in the clinical laboratory,
Chronic lymphocytic leukemia 2 2.4 ± 0.07 but they have not been able to appreciate it fully,
Liposarcoma 1 2.1 since earlier methods were time-consuming and
Fibrocystocytoma 1 2.0
Endometrial 2 1.3 ± 0.14
tedious. With the current availability of the Mal-
Ovarian (with liver metastases) 1 1.2 linckrodt RIA kit, one can now easily incorporate
the FPA evaluation in a hemostatic workup. Cur-
*Plasma samples obtained from the San Joaquin Hematology/
Oncology Group in Bakersfield, California, were collected in rent research is also using FPA levels to develop
special anticoagulant and frozen before assaying. new assays, such as an FPA generating ability of
plasma to assess the capacity of an individual's
whole blood or plasma system to activate thrombin.
TABLE 9. Fibrinopeptide A Levels in Patients w i t h This can be used as a measure of tendency to
Suspected Hypercoagulable States*
develop a hypercoagulable state or in evaluating
Patient FPA (ng/ml) antithrombotic therapy. Figure 8 shows circulating
1 4.2 FPA levels in 23 cases of total hip replacement. As
2 4.6 can be seen, the activation of coagulation reaches a
peak on day 1 and progressively returns to the base-
5 8.2 line level within a week. This method is very useful
6 9.2 in monitoring drugs that are not measurable using
7 23.0 global tests.
FPA can be used as a quality control device for
10 4.2 plasma-based laboratory controls, reagents, and
11 9.0 therapeutic agents. By making use of the extreme
12 6.0 sensitivity of this marker, these products can be
*Patients with deep vein thrombosis, low AT III, shortened PT
and PTT were considered to be hypercoagulable.
cantly higher than the general baseline levels. This
result suggests that all of these patients have some
form of activation of the coagulation system that
results in the generation of FPA.
Table 10 shows the results of FPA levels in
various disorders of fibrinolysis. In ten patients
with malignancy and fibrinolysis a significant in-
crease in the FPA levels was obvious. However, in
secondary fibrinolysis (DIC) a marked increase in
the FPA levels was observed. This suggests that al-
though a nonspecific increase of FPA in the so-
called primary fibrinolysis is observed, the genera- FIG. 8. Circulating fibrinopeptide A levels following total
tion of this marker is much higher in DIC. hip replacement in 23 cases. Average values ± 1 SD.
PERFORMANCE CHARACTERISTICS OF A RIA FOR FPA - WALENGA, ET AL 225
assessed for batch to batch variability in a manu- TABLE 12. Fibrinopeptide A Levels in Various
facturing procedure if activation of the plasma Activated and Nonactivated Prothrombin
would be deleterious to the performance of the pro- Complex Concentrates*
duct. This is an important consideration for plasma Concentrate FPA (ng/ml)
controls used in the newer, more sensitive assays Proplex (Hyland) 7.5 ± 2.0
other than PT and PTT when a defined normal Autoplex (Hyland) 3.5 ± 1.2
plasma is required. An elevated FPA level will indi- Konyne (Cutter) 15.0 ± 19.0
cate that some extent of a thrombotic event has AICC (Cutter) 17.5 ± 4.0
occurred and the plasma is no longer normal. In FEIBA (Immuno) 187.0 ± 19.0
addition, FPA on other activation products may Preconativ (Kabi) 210.6 ± 23.0
exhibit feedback mechanisms on serine proteases in
*All FPA concentrations are expressed as ng/ml/U of the con-
the coagulation network and thus interfere in a centrate. Lyophilized concentrates were diluted with sterile
normal control response. Quality control by FPA water.
will allow a plasma pool to be used as a standard
preparation in assays in which the commercially TABLE 13. Generation of Fibrinopeptide A by
available controls may not provide a normal human Prothrombin Complex Concentrates*
value. Such controls either contain animal products Complex Manufacturer FPA Generated (ng/ml)
or substances from processing that may interfere in
AICC Cutter 1825 ± 247
the newer assays, such as heparin. Table 11 shows
Konyne Cutter 250 ± 1
data from ten individual lots of in-house normal
Proplex Hyland 210 ± 56
human plasma pool preparations. Although these
Autoplex Hyland 612 ± 53
are samples collected in citrate, one can determine a
FEIBA Immuno 412 ± 18
control level for each pool. Additionally, batch to
Preconativ KABI 290 ± 21
batch variations can be evaluated. It is also ap-
parent that if proper venipuncture is carried out, a *A 0.9 ml of normal human plasma (diluted 1:10) was incubated
with 0.1 ml of each prothrombin complex concentrate (50 U/ml
clean, nonactivated pooled control can be obtained for 30 minutes at 37°C. Fibrinopeptide A measurements were
without the proper anticoagulant. However, this is then determined.
not recommended for routine use.
Table 12 shows FPA levels in various commer- the concentrates. The prothrombotic activity of
cially available prothrombin complex concentrates. each concentrate was assessed by its ability to
All concentrates were made to 1 U/ml sterile water generate FPA from the plasma. There is a tremen-
(manufacturer's units) and assayed for FPA. The dous amount of variability between each prepara-
individual manufacturing procedures can be evalu- tion, even after background concentrations (Table
ated for consistency of plasma activation by this 12) are taken into consideration. In this manner,
method. This may or may not be desirable, depend- potency evaluations of each concentrate can be
ing on the use of the product. made.
On the other hand, Table 13 shows data of the
same concentrates but for a modified application of SUMMARY
the FPA quantitation. In this method normal
human plasma was incubated at 37°C with each of FPA, although identified 15 years ago, is now
becoming an increasingly important diagnostic tool
TABLE 11. Fibrinopeptide A Determination in Normal
in the evaluation of the hemostatic process. Since
Human Pool Plasma Preparations* this peptide is generated in very small amounts,
only very sensitive methods, such as RIA, are use-
Preparation Fibrinopeptide A (ng/ml)
ful for its quantitation. Measurement of this
peptide allows for a most precise and reliable
3 2.3 monitor of any ongoing thrombotic event in which
4 1.9 thrombin is generated.
5 3.8 Commercial kits have become available for fast
6 16.1 and simple clinical evaluations of FPA. The Mai-
linckrodt RIA Quanti FPA kit has proved its reli-
9 3.6 ability in precision, accuracy, fast turnaround time,
10 11.0 and applicability to a routine laboratory setting.
*Plasmas were collected in sodium citrate using a double syringe This assay kit was evaluated in our laboratory
technique. No special precautions were taken in specimen in various aspects. The following points summarize
handling. our finding:
226 SEMINARS IN THROMBOSIS AND HEMOSTASIS-VOL. 10, NO. 4, 1984
1. FPA is a useful diagnostic parameter to eval CRM Prentice: Plasma fibrinopeptide A and beta-thrombo-
uate the activation of coagulation pathways globulin in pre-eclampsia and pregnancy hypertension.
Thromb Haemost 47:54-55, 1982.
in various pathologic states.
11. Fareed J, RL Bick, G Squillaci, JM Walenga, EW Bermes:
2. A study of 170 normal plasma samples re Molecular markers of hemostatic disorders: Implications in
sulted in 1.7 ± 0.5 ng/ml. No significant the diagnosis and therapeutic management of thrombotic
difference between males and females was and bleeding disorders. Clin Chem 29:1641-1658, 1983.
noted. 12. Fareed J, HL Messmore, EW Bermes: New perspectives in
coagulation testing. Clin Chem 26:1380-1391, 1980.
3. FPA levels are evaluated in patients with
13. Gaffney PJ, F Joe, M Mahmoud, CA Fossati, M Spitz: A
hypercoagulable states, DIC, and related novel radiometric approach to the assay of components of
thrombotic states. human haemostasis: 1. Assay of plasma fibrinopeptide A
4. Our studies have shown that FPA levels are levels. Thromb Res 19:815-822, 1980.
also elevated in certain cancers, postsurgical 14. Harenberg J, G Stehle, H Schmidt-Gayk, R Zimmermann:
Fibrinopeptide A (FPA) radioimmunoassay influence of the
states, and certain other conditions in which
affinity of the second antibody for FPA antiserum. Thromb
the coagulation process is activated. Res 21:531-532, 1981.
5. During therapeutic heparinization, FPA 15. Harenberg J, G Hepp, H Schmidt-Gayk: Fibrinopeptide A
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The current technologic developments that are
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