Practical Utilization of the Complete Blood Count

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

2. Introduction • Overview of Components of CBC • White Blood Cells • Hemoglobin / Hematocrit • Platelets • Cell Morphology • Secondary Testing

3. Complete Blood Count - CBC • WBC • Hemoglobin / Hematocrit • MCV • RDW • MCHC / MCH • Platelets • Differential Count • Manual • Machine

4. When Assessing CytopeniasAlways Think Three Things • Not making enough • Losing cells • Cell destruction

5. WHITE BLOOD CELLS

6. Blood Cell Formation Stem Cell Proerythoblast Myeloblast Promyelocyte Lymph Plasma Cells Erythrocyte Eosinophil Neutrophil Monocyte Basophil

7. White Blood Cells • Neutrophils • Absolute Neutrophil Count • WBC x Neu% (segmented neutrophils and bands) • Lymphocytes • Monocytes • Eosinophils • Basophils

8. What to Do if WBC Abnormal • Take a Good History • Physical Examination • Look at Old CBC’s!!!!

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

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

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

12. Evaluation of Neutropenia Consider Heme Consult Adapted from Goldman: Cecil Medicine, 23rd ed.

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

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

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

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

17. Lymphocytosis • Infections • Viral • Hepatitis • CMV • Tuberculosis • Addisons Disease • Leukemia • Ulcerative Colitis / Crohn’s Disease • Vasculitis • Drug Hypersensitivity

18. Lymphopenia • Increased Destruction • Corticosteroids • Congestive Heart Failure • Loss through GI tract • Decreased Production • Malignancies • Immunoglobulin Disorders • HIV Infection • Lupus

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

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

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

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

23. MCVFalsely Abnormal • Cold Agglutinins • Hyperglycemia • Reticulocytosis • Leukocytosis • Acute Hemolysis

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

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

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

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

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

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

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

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

32. Evaluation of Macrocytosis • History • Physical • False Macrocytosis • Cold agglutinins: RBC clumping • Hyperglycemia: Hyperosmolarity • Leukocytosis: WBC counted as RBC

33. Evaluation of Macrocytosis • B12 / Folate • Look for hypersegmented neutrophils • Thyroid Studies • If clinically indicated • Liver Associated Enzymes • Reticulocyte Count

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

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

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

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

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

39. Normocytic AnemiaDifferential Diagnosis • Acute Hemorrhage • Hemolysis • Aplastic Anemia • Renal Failure • Myelophthisis • Sickle cell anemia • Chronic Disease • Combined Microcytosis / Macrocytosis

40. Normocytic AnemiaEvaluation • Clinical History • Review CBC for multiple Cell line deficiencies • RDW / Smear • Malnutrition • Direct Antibody Test • Chemistries • Consider Bone Marrow Biopsy

41. Red Blood Cells • Spherocytes • Sickle Cells • Schistocytes • Tear Drop Cells • Basophilic Stippling • Howell-Jolly Bodies

42. SchistocytesDifferential Diagnosis • Mechanical Valves • Stenotic Valves • Malignant Hypertension • Disseminated Intravascular Coagulation DIC • Hemolytic Uremic Syndrome – HUS • Thrombotic Thrombocytopenic Purpura

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

44. Thrombocytopenia • Decreased Production • Acute Infection • Increased Destruction • Consumption • Primary or Hereditary

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

46. Pseudothrombocytopenia • EDTA related platelet clumping • Clinically insignificant • Cold Agglutinins • Giant Platelets • Erythrocytosis

47. Idiopathic Thrombocytopenic Purpura • IDIOPATHIC • Bleeding unlikely unless < 10,000 • Diagnosis of exclusion • Bone marrow biopsy necessary only in those > 60 years old

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