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Practical Utilization of the Complete Blood Count - Joseph M. Flynn, D.O.,M...


Introduction. Overview of Components of CBCWhite Blood CellsHemoglobin / HematocritPlateletsCell MorphologySecondary Testing. Complete Blood Count - CBC. WBCHemoglobin / HematocritMCVRDWMCHC / MCHPlateletsDifferential CountManual Machine. When Assessing Cytopenias Always Think Three Thi

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Practical Utilization of the Complete Blood Count

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Practical utilization of the complete blood count l.jpg

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 l.jpg

Introduction

  • Overview of Components of CBC

  • White Blood Cells

  • Hemoglobin / Hematocrit

  • Platelets

  • Cell Morphology

  • Secondary Testing


Complete blood count cbc l.jpg

Complete Blood Count - CBC

  • WBC

  • Hemoglobin / Hematocrit

  • MCV

  • RDW

  • MCHC / MCH

  • Platelets

  • Differential Count

    • Manual

    • Machine


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When Assessing CytopeniasAlways Think Three Things

  • Not making enough

  • Losing cells

  • Cell destruction


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WHITE BLOOD CELLS


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Blood Cell Formation

Stem Cell

Proerythoblast

Myeloblast

Promyelocyte

Lymph

Plasma

Cells

Erythrocyte

Eosinophil

Neutrophil

Monocyte

Basophil


White blood cells l.jpg

White Blood Cells

  • Neutrophils

    • Absolute Neutrophil Count

      • WBC x Neu% (segmented neutrophils and bands)

  • Lymphocytes

  • Monocytes

  • Eosinophils

  • Basophils


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What to Do if WBC Abnormal

  • Take a Good History

  • Physical Examination

  • Look at Old CBC’s!!!!


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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


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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 l.jpg

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


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Evaluation of Neutropenia

Consider Heme Consult

Adapted from Goldman: Cecil Medicine, 23rd ed.


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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


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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


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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


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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


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Lymphocytosis

  • Infections

    • Viral

      • Hepatitis

      • CMV

    • Tuberculosis

  • Addisons Disease

  • Leukemia

  • Ulcerative Colitis / Crohn’s Disease

  • Vasculitis

  • Drug Hypersensitivity


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Lymphopenia

  • Increased Destruction

    • Corticosteroids

  • Congestive Heart Failure

    • Loss through GI tract

  • Decreased Production

    • Malignancies

    • Immunoglobulin Disorders

    • HIV Infection

    • Lupus


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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


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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


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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 l.jpg

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


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MCVFalsely Abnormal

  • Cold Agglutinins

  • Hyperglycemia

  • Reticulocytosis

  • Leukocytosis

  • Acute Hemolysis


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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


Rdw vs mcv25 l.jpg

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


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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


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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


Iron deficiency l.jpg

Iron Deficiency

  • Most common cause of microcytosis

  • Clinical Clues

  • Iron Studies

    • Iron

    • Total Iron Binding Capacity

    • Ferritin

  • Iron Saturation (Serum Iron / TIBC )

    • < 10 % saturation


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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


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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


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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


Evaluation of macrocytosis l.jpg

Evaluation of Macrocytosis

  • History

  • Physical

  • False Macrocytosis

    • Cold agglutinins: RBC clumping

    • Hyperglycemia: Hyperosmolarity

    • Leukocytosis: WBC counted as RBC


Evaluation of macrocytosis33 l.jpg

Evaluation of Macrocytosis

  • B12 / Folate

    • Look for hypersegmented neutrophils

  • Thyroid Studies

    • If clinically indicated

  • Liver Associated Enzymes

  • Reticulocyte Count


Megaloblastic anemia l.jpg

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 l.jpg

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


Diagnosing vitamin deficiencies l.jpg

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


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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


Slide38 l.jpg

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


Normocytic anemia differential diagnosis l.jpg

Normocytic AnemiaDifferential Diagnosis

  • Acute Hemorrhage

  • Hemolysis

  • Aplastic Anemia

  • Renal Failure

  • Myelophthisis

  • Sickle cell anemia

  • Chronic Disease

  • Combined Microcytosis / Macrocytosis


Normocytic anemia evaluation l.jpg

Normocytic AnemiaEvaluation

  • Clinical History

  • Review CBC for multiple Cell line deficiencies

  • RDW / Smear

    • Malnutrition

  • Direct Antibody Test

  • Chemistries

  • Consider Bone Marrow Biopsy


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Red Blood Cells

  • Spherocytes

  • Sickle Cells

  • Schistocytes

  • Tear Drop Cells

  • Basophilic Stippling

  • Howell-Jolly Bodies


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SchistocytesDifferential Diagnosis

  • Mechanical Valves

  • Stenotic Valves

  • Malignant Hypertension

  • Disseminated Intravascular Coagulation DIC

  • Hemolytic Uremic Syndrome – HUS

  • Thrombotic Thrombocytopenic Purpura


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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


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Thrombocytopenia

  • Decreased Production

  • Acute Infection

  • Increased Destruction

  • Consumption

  • Primary or Hereditary


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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


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Pseudothrombocytopenia

  • EDTA related platelet clumping

    • Clinically insignificant

  • Cold Agglutinins

  • Giant Platelets

  • Erythrocytosis


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Idiopathic Thrombocytopenic Purpura

  • IDIOPATHIC

  • Bleeding unlikely unless < 10,000

  • Diagnosis of exclusion

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


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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