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Practical Utilization of the Complete Blood Count






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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
Practical Utilization of the Complete Blood Count

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Slide 1

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

Slide 2

Introduction

  • Overview of Components of CBC

  • White Blood Cells

  • Hemoglobin / Hematocrit

  • Platelets

  • Cell Morphology

  • Secondary Testing

Slide 3

Complete Blood Count - CBC

  • WBC

  • Hemoglobin / Hematocrit

  • MCV

  • RDW

  • MCHC / MCH

  • Platelets

  • Differential Count

    • Manual

    • Machine

Slide 4

When Assessing CytopeniasAlways Think Three Things

  • Not making enough

  • Losing cells

  • Cell destruction

Slide 5

WHITE BLOOD CELLS

Slide 6

Blood Cell Formation

Stem Cell

Proerythoblast

Myeloblast

Promyelocyte

Lymph

Plasma

Cells

Erythrocyte

Eosinophil

Neutrophil

Monocyte

Basophil

Slide 7

White Blood Cells

  • Neutrophils

    • Absolute Neutrophil Count

      • WBC x Neu% (segmented neutrophils and bands)

  • Lymphocytes

  • Monocytes

  • Eosinophils

  • Basophils

Slide 8

What to Do if WBC Abnormal

  • Take a Good History

  • Physical Examination

  • Look at Old CBC’s!!!!

Slide 9

Neutrophils

  • 60 - 70 % of Circulating Leukocytes

  • Half Life

    • Six to Seven Hours in blood

    • One to Two Days in Connective Tissue

  • Primary Defense against Bacteria

Slide 10

Neutrophils

  • Neutropenia

    • Absolute Neutrophil Count < 1500

      • (Often < 1000 in African Americans)

  • Neutrophilia

    • Absolute Neutrophil Count > 8000

  • Leukemoid Reaction

    • Elevation in WBC

      • Typically < 50,000

Slide 11

Decreased Production

Infections

Severe Bacterial

Viral

Rickettsial

Drugs

Antibiotics

NSAIDS

Others

Hematological Disease

Dietary

Shock

Severe Renal Disease

Decreased Survival

Infections

Drugs

Immune mediated

SLE

Cyclic

Neutropenia

Slide 12

Evaluation of Neutropenia

Consider Heme Consult

Adapted from Goldman: Cecil Medicine, 23rd ed.

Slide 13

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

Slide 14

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

Slide 15

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

Slide 16

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

Slide 17

Lymphocytosis

  • Infections

    • Viral

      • Hepatitis

      • CMV

    • Tuberculosis

  • Addisons Disease

  • Leukemia

  • Ulcerative Colitis / Crohn’s Disease

  • Vasculitis

  • Drug Hypersensitivity

Slide 18

Lymphopenia

  • Increased Destruction

    • Corticosteroids

  • Congestive Heart Failure

    • Loss through GI tract

  • Decreased Production

    • Malignancies

    • Immunoglobulin Disorders

    • HIV Infection

    • Lupus

Slide 19

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

Slide 20

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

Slide 21

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

Slide 22

Increased:

Increased WBC

WBC >50,000

Smoking

Dehydration

Triglycerides

>2000

Decreased

Position

Pregnancy

Diurnal

Race

Females

IV fluids

Changes in HgbNot Due to Blood Loss or Abherrent Condition

Slide 23

MCVFalsely Abnormal

  • Cold Agglutinins

  • Hyperglycemia

  • Reticulocytosis

  • Leukocytosis

  • Acute Hemolysis

Slide 24

Normal RDW ; Low MCV

Thalassemia

Chronic Disease

Normal RDW ; High MCV

Aplastic Anemia

Myelodysplasia

Alcohol

Normal RDW ; Normal MCV

Chronic disease (90%)

Hereditary Spherocytosis

Acute Bleed

Cirrhosis

Uremia

RDW vs MCV

Adapted: Ravel; 1995; 14

Slide 25

HIGH RDW ; Low MCV

Iron Deficiency

S-Thalassemia

RBC fragmentation

HIGH RDW ; HIGH MCV

B12/Folate

Autoimmune hemolysis

Cold Agglutinins

HIGH RDW ; Normal MCV

Early Factor Deficiency

SS disease

SC dz

Sideroblastic anemia

Myelofibrosis

RDW vs MCV

Slide 26

Pathophysiologic ClassificationAnemia

  • 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

Slide 27

MicrocytosisDifferential 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

Slide 28

Iron Deficiency

  • Most common cause of microcytosis

  • Clinical Clues

  • Iron Studies

    • Iron

    • Total Iron Binding Capacity

    • Ferritin

  • Iron Saturation (Serum Iron / TIBC )

    • < 10 % saturation

Slide 29

Iron

Serum Iron TIBC Ferritin

Iron Deficiency

Sideroblastic

Thalassemia

Anemia of Chronic

Disease

Low

Elevated

Elevated

Low

Elevated

Nml

Nml

Low

Low

Elevated

Elevated

Elevated

Slide 30

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

Slide 31

MacrocytosisMCV > 100

  • Folate/B12 20 - 30%

  • Chronic Liver dx 15 - 20% **

  • Alcoholism 10 - 12% -

  • Chemotherapy 10 - 15%

  • Reticulocytosis 7%

  • Myelodysplastic Common

  • Unknown 25%

  • Distance runners

  • Hypothyroidism **

  • Hyperlipidemia **

Can occur with 1bottle

of wine per day

**Lipid membrane defects

Slide 32

Evaluation of Macrocytosis

  • History

  • Physical

  • False Macrocytosis

    • Cold agglutinins: RBC clumping

    • Hyperglycemia: Hyperosmolarity

    • Leukocytosis: WBC counted as RBC

Slide 33

Evaluation of Macrocytosis

  • B12 / Folate

    • Look for hypersegmented neutrophils

  • Thyroid Studies

    • If clinically indicated

  • Liver Associated Enzymes

  • Reticulocyte Count

Slide 34

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

Slide 35

Megaloblastic AnemiaDiagnosis

  • 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

Slide 36

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

Slide 37

Diagnosing Vitamin Deficiencies

  • Methylmalonic acid and Homocysteine

    • Good if Cobalamin and Folate are equivocal

    • Both elevated = Cobalamin Deficiency

      • 95% Sensitivity

      • 99% Specificity

    • If Homocysteine only elevated = Folate Deficiency

      • 85% Sensitivity

  • Anti-Intrinsic factor Antibodies Confirms Pernicious Anemia

Slide 38

MCV >100

Consider Lab

Error

Rule out Drugs

Retic ct

High

LFT’s

Thyroid

B12 &

Folate

LOW

Blood Loss

Eval for

Hemolysis

Normal

MMA & HC

LDH

Bilirubin

Haptoglobin

Most commonly

Myelodysplasia

Consider Bmbx

Adapted from Colon-Otero, Med Clin of NA. 76(3)581-596. 1992

Slide 39

Normocytic AnemiaDifferential Diagnosis

  • Acute Hemorrhage

  • Hemolysis

  • Aplastic Anemia

  • Renal Failure

  • Myelophthisis

  • Sickle cell anemia

  • Chronic Disease

  • Combined Microcytosis / Macrocytosis

Slide 40

Normocytic AnemiaEvaluation

  • Clinical History

  • Review CBC for multiple Cell line deficiencies

  • RDW / Smear

    • Malnutrition

  • Direct Antibody Test

  • Chemistries

  • Consider Bone Marrow Biopsy

Slide 41

Red Blood Cells

  • Spherocytes

  • Sickle Cells

  • Schistocytes

  • Tear Drop Cells

  • Basophilic Stippling

  • Howell-Jolly Bodies

Slide 42

SchistocytesDifferential Diagnosis

  • Mechanical Valves

  • Stenotic Valves

  • Malignant Hypertension

  • Disseminated Intravascular Coagulation DIC

  • Hemolytic Uremic Syndrome – HUS

  • Thrombotic Thrombocytopenic Purpura

Slide 43

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

Slide 44

Thrombocytopenia

  • Decreased Production

  • Acute Infection

  • Increased Destruction

  • Consumption

  • Primary or Hereditary

Slide 45

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

Slide 46

Pseudothrombocytopenia

  • EDTA related platelet clumping

    • Clinically insignificant

  • Cold Agglutinins

  • Giant Platelets

  • Erythrocytosis

Slide 47

Idiopathic Thrombocytopenic Purpura

  • IDIOPATHIC

  • Bleeding unlikely unless < 10,000

  • Diagnosis of exclusion

  • Bone marrow biopsy necessary only in those > 60 years old

Slide 48

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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