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Complete Blood Count (CBC): A Comprehensive Guide

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1. How the CBC is Performed

• Electrical impedance (Coulter principle): Cells passing through an aperture displace electrolyte, generating a pulse proportional to cell volume.
• Light scatter (flow cytometry): Laser light hitting each cell produces forward scatter (cell size) and side scatter (internal complexity/granularity), used to generate the 5-part differential.

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2. Components of the CBC

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🔴 Part A: Red Blood Cell (RBC) Parameters

2.1 Hemoglobin (Hgb/Hb)

• Anemia = Hgb < 12 g/dL (females) or < 13.5 g/dL (males). Pallor of conjunctival mucosa generally indicates Hgb < 9 g/dL; failure of palmar creases to redden indicates Hgb ≤ 7–8 g/dL.
• Polycythemia/Erythrocytosis = Hgb elevated, may indicate primary (polycythemia vera) or secondary causes (renal carcinoma, hepatocellular carcinoma, high altitude, COPD, androgens, exogenous EPO, postrenal transplant, polycystic kidney disease).

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2.2 Hematocrit (Hct / PCV)

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2.3 RBC Count

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2.4 Red Cell Indices

• High MCV (macrocytosis) → B12/folate deficiency, hypothyroidism, alcohol, liver disease, reticulocytosis, drugs (hydroxyurea, methotrexate)
• Low MCV (microcytosis) → iron deficiency anemia (IDA), thalassemia, anemia of chronic disease (some)
• High MCHC → hereditary spherocytosis, cold agglutinins, lipemic specimens
• RDW high in IDA, normal in thalassemia — a key distinguishing point: thalassemia minor produces uniform microcytosis (low MCV, normal RDW); IDA produces variable microcytosis (low MCV, elevated RDW)
• Pronounced reticulocytosis can raise the MCV (reticulocytes are larger than mature RBCs)

Anemia Classification by MCV:

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2.5 Reticulocyte Count

• Absolute reticulocyte count = % reticulocytes × RBC count
• Corrected reticulocyte count (CRC) = % retics × (patient Hct / 45)
• RPI = CRC / maturation factor (maturation factor: 1.0 at Hct 36–45%, 1.5 at 26–35%, 2.0 at 16–25%, 2.5 at ≤15%)

• RPI > 3: Adequate marrow response → hemorrhage or hemolysis (hyperproliferative)
• RPI < 2: Inadequate marrow response → hypoproliferative anemia (iron deficiency, B12/folate, aplastic anemia, renal failure)

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2.6 RDW — Red Cell Distribution Width

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⚪ Part B: White Blood Cell (WBC) Parameters

2.7 Total WBC Count

Leukocytosis (WBC > 10,000/mm³):

Leukopenia (WBC < 4,000/mm³):

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2.8 The 5-Part Differential

• ANC < 1500/μL = neutropenia
• ANC < 500/μL = severe neutropenia → high risk of life-threatening bacterial infections

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🟡 Part C: Platelet Parameters

2.9 Platelet Count

• Decreased production: aplastic anemia, myelophthisis, chemotherapy, alcohol, B12/folate deficiency
• Increased destruction: ITP, TTP/HUS, DIC, heparin-induced thrombocytopenia (HIT — typically drops to 50,000–70,000 within 5–15 days of heparin)
• Sequestration: hypersplenism

• Reactive: infection, iron deficiency, post-splenectomy, inflammatory disorders, hemorrhage
• Primary: essential thrombocythemia (ET), CML, polycythemia vera

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2.10 Mean Platelet Volume (MPV)

• High MPV → large platelets from marrow, indicating peripheral destruction/consumption (e.g., ITP, HIT) — the marrow is producing young, large platelets to compensate
• Low MPV → suggests decreased production (aplastic anemia, marrow infiltration)

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3. Additional / Extended CBC Parameters

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4. Anemia: CBC-Based Diagnostic Algorithm

Low Hemoglobin → Is it hypoproliferative or hyperproliferative?
         ↓
   Check RPI / Reticulocyte count
         ↓
RPI < 2 (hypoproliferative)          RPI > 3 (hyperproliferative)
  → Check MCV:                          → Hemolysis or blood loss
    Low MCV → IDA, thalassemia,           → Check LDH, bilirubin,
               sideroblastic anemia          haptoglobin, peripheral smear
    Normal MCV → ACD, aplastic,
                 renal failure
    High MCV → B12/folate, alcohol,
               hypothyroidism, MDS

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5. Key CBC Patterns and Their Diagnoses

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6. Race, Sex, and Age Effects on Reference Ranges

• Hematocrit, Hgb, and MCV are lower in African Americans than Caucasians
• Hematocrit, Hgb, MCH, MCHC, and MPV are lower in Asians than Caucasians
• Children have higher WBC and lymphocyte counts relative to adults
• Pregnant women have physiological dilutional anemia (expanded plasma volume)
• Elderly patients may have slightly lower RBC counts and slightly altered WBC differential

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7. Common Pitfalls and Spurious Results

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8. When to Order a CBC

• Suspected or known anemia (fatigue, pallor, dyspnea)
• Infection workup (fever, suspected sepsis)
• Bleeding or bruising disorders
• Preoperative assessment
• Monitoring chemotherapy, radiation therapy, or myelosuppressive drugs
• Diagnosis and monitoring of hematologic malignancies
• Evaluation of systemic inflammatory disorders
• Screening in pregnancy, pediatric well-visits
• Baseline prior to starting medications that affect marrow (e.g., clozapine, carbamazepine, methotrexate)

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Summary Table: All CBC Parameters at a Glance

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• Goldman-Cecil Medicine, 26th ed., Chapter 144 (Approach to Anemia; Complete Blood Counts)
• Quick Compendium of Clinical Pathology, 5th ed., Sections 4.4.1–4.4.3 (Methods: RBC, Leukocyte, Platelet Indices)
• Textbook of Family Medicine, 9th ed., Chapter 14 (White Blood Cells, Platelets, Erythrocytosis)
• Tietz Textbook of Laboratory Medicine, 7th ed. (Reference intervals, analyzer technology)