The Peripheral Smear for the Internist.PPT by tongxiamy

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									Practical Utilization of the
 Complete Blood Count
   Joseph M. Flynn, D.O.,MPH, FACP
     Division Hematology-Oncology
       THE Ohio State University
             Columbus, OH
             April 18, 2008
          Introduction

 Overview of Components of CBC
 White Blood Cells
 Hemoglobin / Hematocrit
 Platelets
 Cell Morphology
 Secondary Testing
    Complete Blood Count - CBC

   WBC
   Hemoglobin / Hematocrit
   MCV
   RDW
   MCHC / MCH
   Platelets
   Differential Count
     Manual
     Machine
   When Assessing Cytopenias
   Always Think Three Things


 Not making enough
 Losing cells
 Cell destruction
WHITE BLOOD CELLS
             Blood Cell Formation
                         Stem Cell
Proerythoblast

                               Myeloblast

                               Promyelocyte




                                                     Lymph
                                                     Plasma
Erythrocyte                                          Cells
         Eosinophil   Neutrophil     Basophil Monocyte
           White Blood Cells

   Neutrophils
    Absolute   Neutrophil Count
        WBC x Neu% (segmented neutrophils and
         bands)
 Lymphocytes
 Monocytes
 Eosinophils
 Basophils
What to Do if WBC Abnormal
 Take a Good History
 Physical Examination


Look      at Old CBC’s!!!!
               Neutrophils

 60 - 70 % of Circulating Leukocytes
 Half Life
    Sixto Seven Hours in blood
    One to Two Days in Connective Tissue

   Primary Defense against Bacteria
                  Neutrophils

   Neutropenia
    Absolute    Neutrophil Count < 1500
        (Often < 1000 in African Americans)
   Neutrophilia
    Absolute    Neutrophil Count > 8000
   Leukemoid Reaction
    Elevation   in WBC
        Typically < 50,000
                       Neutropenia
   Decreased Production             Decreased Survival
     Infections                       Infections
         Severe Bacterial
                                       Drugs
         Viral
         Rickettsial                  Immune   mediated
     Drugs                            SLE
        Antibiotics                   Cyclic
        NSAIDS
        Others
     Hematological     Disease
     Dietary
     Shock
     Severe    Renal Disease
                       Evaluation of Neutropenia




                                                 Consider Heme Consult



Adapted from Goldman: Cecil Medicine, 23rd ed.
    Benign (Ethnic) Neutropenia

   Characterized by neutrophil counts 800 to
    1400/mm3
   Generally a benign course
     Sometimes  associated with periodontal disease
     No increase in infections

   Bone marrow is typically normocellular
   Seen in African American, some Jewish
    populations
                  Neutrophilia
   Acute Infections
     Leukocyte:    15-25 X 109/L.
   Inflammation
     Postoperatively, neutrophilia occurs for 12-36
      hours as a result of tissue injury
   Metabolic
     Uremia,
     DKA
     Eclampsia
   Chemicals
     Steroids
     Epinephrine
                  Neutrophilia
   Acute Hemorrhage
     Related to the release of adrenal corticosteroids
      and/or epinephrine
   Acute Hemolysis
   Myeloproliferative disorders
   Tissue Injury
   Tobacco Use
   Physiological Stress
     Exercise
     Emotional Stress
     Menstruation
            Steroid Effect

 Increases total and relative PMN’s
 Peak is 4-6 hours
 Normalizes in 24 hours after steroids
  stopped
 Usually see a concurrent decrease in
  Lymphocytes and Monocytes
             Lymphocytosis
   Infections
     Viral
        Hepatitis
        CMV
     Tuberculosis
   Addisons Disease
   Leukemia
   Ulcerative Colitis / Crohn’s Disease
   Vasculitis
   Drug Hypersensitivity
                  Lymphopenia

   Increased Destruction
     Corticosteroids
   Congestive Heart Failure
     Loss   through GI tract
   Decreased Production
     Malignancies
     Immunoglobulin    Disorders
     HIVInfection
     Lupus
                 Eosinophilia
   > 250/ CU MM
   Highest Levels in am
   Allergic Diseases
   Parasitic Infections: Trichinosis, Schistosomiasis
   Leukemias
   Familial
   Addison’s Disease, Hypopituitarism
   Drugs: Aspirin
   Collagen Vascular Diseases: Churg-Strauss,
    Scleroderma/dermatomyositis, RA, SLE,
    Periarteritis Nodosa
                  Monocytosis
   > 10% of differential
   Elevated in:
     Leukemia
     Hodgkins   / Non Hodgkins lymphoma
     Post Splenectomy
     Protozoan Infections
     Rickettsial Infections: Rocky Mountain Fever, Typhus
     Sarcoidosis
     Collagen Vascular Diseases
     Enteritis
                 Hemoglobin

   Boys and girls are same until @ age 11
    Boys  values slowly become higher
    Adult levels reached
        Age 15 Women
        Age 18 Men
    African Americans 0.5 - 1.0gm (5-10 g/dL)
     lower than northern Europeans
    Positional differences
        Upright vs post bedtime
                 Changes in Hgb
Not Due to Blood Loss or Abherrent Condition

   Increased:             Decreased
    Increased    WBC       Position
        WBC >50,000        Pregnancy
    Smoking                Diurnal
    Dehydration            Race
    Triglycerides          Females
        >2000              IV   fluids
                MCV
          Falsely Abnormal

 Cold Agglutinins
 Hyperglycemia
 Reticulocytosis
 Leukocytosis
 Acute Hemolysis
                  RDW vs MCV

   Normal RDW ; Low                              Normal RDW ;
    MCV                                            Normal MCV
     Thalassemia                                   Chronic   disease
     Chronic    Disease                             (90%)
                                                    Hereditary
   Normal RDW ; High
                                                     Spherocytosis
    MCV
                                                    Acute Bleed
     AplasticAnemia
                                                    Cirrhosis
     Myelodysplasia
                                                    Uremia
     Alcohol

                    Adapted: Ravel; 1995; 14
               RDW vs MCV

   HIGH RDW ; Low           HIGH RDW ; Normal
    MCV                       MCV
     IronDeficiency           Early Factor
     S-Thalassemia             Deficiency
     RBC fragmentation        SS disease
                               SC dz
   HIGH RDW ; HIGH
                               Sideroblastic anemia
    MCV
                               Myelofibrosis
     B12/Folate
     Autoimmune
      hemolysis
     Cold Agglutinins
    Pathophysiologic Classification
              Anemia

 Due to Decreased RBC Production
 Due to RBC Destruction
    0.8  % rbc’s destroyed daily
    Best suited for relating disease processes
     to their mechanisms
    Limited in the complexity of mechanisms
     and lack of solidly established mechanisms
             Microcytosis
        Differential Diagnosis

 Iron Deficiency
 Thalassemia
    Beta-Thalassemia: Elevated Hgb A2 or F
    alpha Thalassemia diagnosis of exclusion
   Anemia of Chronic Disease
    Though   75% patients are normocytic
 Sideroblastic anemia - rare
 Lead poisoning - rare
             Iron Deficiency

 Most common cause of microcytosis
 Clinical Clues
 Iron Studies
    Iron
    Total Iron Binding Capacity
   Ferritin
 Iron Saturation (Serum Iron / TIBC )
   < 10 % saturation
                       Iron
                    Serum Iron    TIBC      Ferritin

Iron Deficiency      Low         Elevated    Low

Sideroblastic        Elevated    Nml         Elevated

Thalassemia          Elevated    Nml         Elevated

Anemia of Chronic    Low         Low         Elevated
Disease
    When Do I Get a Hemoglobin
         Electropheresis

 Iron studies not indicative of another
  process
 Family history of hemoglobinopathy
 African American
 Asian decent
 Mediterranean decent
 Microcytosis in face of mild-No
  anemia
                 Macrocytosis
                  MCV > 100
   Folate/B12          20 - 30%
   Chronic Liver dx    15 - 20% **
   Alcoholism          10 - 12% - Can occur with 1bottle
                                   of wine per day
   Chemotherapy        10 - 15%
   Reticulocytosis     7%
   Myelodysplastic     Common
   Unknown                   25%
   Distance runners
   Hypothyroidism **        **Lipid membrane defects

   Hyperlipidemia **
    Evaluation of Macrocytosis

 History
 Physical
 False Macrocytosis
    Coldagglutinins: RBC clumping
    Hyperglycemia: Hyperosmolarity
    Leukocytosis: WBC counted as RBC
     Evaluation of Macrocytosis

   B12 / Folate
    Look     for hypersegmented neutrophils
   Thyroid Studies
    If   clinically indicated
 Liver Associated Enzymes
 Reticulocyte Count
           Megaloblastic Anemia

     Hypersegmented Neutrophils
      Any neutrophil with > six segments or
      More than five percent with five segments
       or
      Majority of cells with four segments

     Presence of Macroovalocytes
      Egg   - shaped cells

The combination is a result of absence of terminal divisions
of marrow precursors
             Megaloblastic Anemia
                  Diagnosis

   Serum folate levels may be misleading
     Alcohol lowers the folate levels
     Correcting serum folate can be seen after a meal

   Determine the cause of the deficiency
     Ie.   Pernicious anemia, Malabsorption, Diet
   Red cell changes are not seen in all vitamin
    deficient patients
     MCV   usually > 110 though > 130 more specific
     Look at RDW
     Cell Morphology
    Diagnosing Vitamin Deficiencies
   Serum cobalamin
    < 200 pg/ml: consistent with Cobalamin
     deficiency
    >300 pg/ml: Normal

   Serum folate concentrations
    If Folate is >4ng/ml then not folate deficient
    If Folate is < 2ng/ml then folate deficient
    If Borderline, Check Red blood cell levels
    Diagnosing Vitamin Deficiencies
   Methylmalonic acid and Homocysteine
    Good  if Cobalamin and Folate are equivocal
    Both elevated = Cobalamin Deficiency
        95% Sensitivity
        99% Specificity
    IfHomocysteine only elevated = Folate
      Deficiency
        85% Sensitivity
   Anti-Intrinsic factor Antibodies Confirms
    Pernicious Anemia
                               MCV >100
  Consider Lab
     Error                  Rule out Drugs




  Retic ct                                                     LFT’s
  High                               B12 &
                                                    LOW        Thyroid
                                     Folate
             Blood Loss
Eval for                            Normal
Hemolysis
                                 MMA & HC
LDH
Bilirubin                                                 Most commonly
Haptoglobin                    Consider Bmbx              Myelodysplasia
Adapted from Colon-Otero, Med Clin of NA. 76(3)581-596. 1992
         Normocytic Anemia
        Differential Diagnosis
   Acute Hemorrhage
   Hemolysis
   Aplastic Anemia
   Renal Failure
   Myelophthisis
   Sickle cell anemia
   Chronic Disease
   Combined Microcytosis / Macrocytosis
         Normocytic Anemia
            Evaluation

 Clinical History
 Review CBC for multiple Cell line
  deficiencies
 RDW / Smear
    Malnutrition
 Direct Antibody Test
 Chemistries
 Consider Bone Marrow Biopsy
           Red Blood Cells

 Spherocytes
 SickleCells
 Schistocytes
 Tear Drop Cells
 Basophilic Stippling
 Howell-Jolly Bodies
               Schistocytes
           Differential Diagnosis

 Mechanical Valves
 Stenotic Valves
 Malignant Hypertension
 Disseminated Intravascular Coagulation
  DIC
 Hemolytic Uremic Syndrome – HUS
   Thrombotic Thrombocytopenic Purpura
                 Platelets

 Size should be <1/3 that of RBC
 Thrombocytopenia: < 150,000
    < 100,000 is important number
    Should be suspected when platelets are
     found in <1 in 10 fields on high power
 Thrombocytosis: >450,000/cu mm
 Pseudothrombocytopenia
        Thrombocytopenia

 Decreased Production
 Acute Infection
 Increased Destruction
 Consumption
 Primary or Hereditary
         Thrombocytopenia

 > 50,000: Typically no bleeding
 20 – 50,000: Post operative bleeding
  and minor mucosal bleeding
 5 – 20,000: Can have significant
  bleeding
 <5,000: Severe bleeding possible
    Unless   ITP
      Pseudothrombocytopenia

   EDTA related platelet clumping
    Clinically   insignificant
 Cold Agglutinins
 Giant Platelets
 Erythrocytosis
    Idiopathic Thrombocytopenic
               Purpura

 IDIOPATHIC
 Bleeding unlikely unless < 10,000
 Diagnosis of exclusion
 Bone marrow biopsy necessary only in
  those > 60 years old
                Thrombocytosis
   Infection
     Acute Phase Reactant
     1/3 of patients
   Inflammatory State
   Malignancy
   Recent Surgery
   Iron Deficiency Anemia
   Trauma
   Myeloproliferative Disorder
     >600,000   on two occasions

								
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