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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
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Introduction Overview of Components of CBC White Blood Cells
Hemoglobin / Hematocrit Platelets Cell Morphology Secondary Testing
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Complete Blood Count - CBC
WBC Hemoglobin / Hematocrit MCV RDW MCHC / MCH Platelets Differential Count Manual Machine
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When Assessing Cytopenias Always 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 Basophil Monocyte
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White Blood Cells Neutrophils Lymphocytes Monocytes Eosinophils
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 Neutrophilia Leukemoid Reaction
Absolute Neutrophil Count < 1500 (Often < 1000 in African Americans) Neutrophilia Absolute Neutrophil Count > 8000 Leukemoid Reaction Elevation in WBC Typically < 50,000
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Neutropenia Decreased Production Decreased Survival Infections
Severe Bacterial Viral Rickettsial Drugs Antibiotics NSAIDS Others Hematological Disease Dietary Shock Severe Renal Disease Decreased Survival Infections Drugs Immune mediated SLE Cyclic
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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 Inflammation Metabolic Chemicals
Leukocyte: X 109/L. Inflammation Postoperatively, neutrophilia occurs for hours as a result of tissue injury Metabolic Uremia, DKA Eclampsia Chemicals Steroids Epinephrine
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Neutrophilia Acute Hemorrhage Acute Hemolysis
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 Addisons Disease Leukemia
Viral Hepatitis CMV Tuberculosis Addisons Disease Leukemia Ulcerative Colitis / Crohn’s Disease Vasculitis Drug Hypersensitivity
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Lymphopenia Increased Destruction Congestive Heart Failure
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 gm (5-10 g/dL) lower than northern Europeans Positional differences Upright vs post bedtime
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Changes in Hgb Not Due to Blood Loss or Abherrent Condition
Increased: Increased WBC WBC >50,000 Smoking Dehydration Triglycerides >2000 Decreased Position Pregnancy Diurnal Race Females IV fluids
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MCV Falsely Abnormal Cold Agglutinins Hyperglycemia Reticulocytosis
Leukocytosis Acute Hemolysis
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RDW vs MCV Normal RDW ; Low MCV Normal RDW ; High 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 Adapted: Ravel; 1995; 14
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RDW vs MCV HIGH RDW ; Low MCV HIGH RDW ; HIGH 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
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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
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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
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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 Nml Low Low 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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Macrocytosis MCV > 100 Folate/B12 20 - 30%
Chronic Liver dx % ** Alcoholism % - Chemotherapy % Reticulocytosis 7% Myelodysplastic Common Unknown 25% Distance runners Hypothyroidism ** Hyperlipidemia ** Can occur with 1bottle of wine per day **Lipid membrane defects
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Evaluation of Macrocytosis
History Physical False Macrocytosis Cold agglutinins: RBC clumping Hyperglycemia: Hyperosmolarity Leukocytosis: WBC counted as RBC
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Evaluation of Macrocytosis
B12 / Folate Look for hypersegmented neutrophils Thyroid Studies If clinically indicated Liver Associated Enzymes Reticulocyte Count
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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
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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
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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
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Consider Lab Error Retic ct LFT’s High B12 & Thyroid Folate LOW
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)
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Normocytic Anemia Differential Diagnosis
Acute Hemorrhage Hemolysis Aplastic Anemia Renal Failure Myelophthisis Sickle cell anemia Chronic Disease Combined Microcytosis / Macrocytosis
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Normocytic Anemia Evaluation
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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Schistocytes Differential 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
Bleeding unlikely unless < 10,000 Diagnosis of exclusion Bone marrow biopsy necessary only in those > 60 years old
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Thrombocytosis Infection Inflammatory State Malignancy Recent Surgery
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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