Complete Blood Count with Differential: Components, Reference Ranges, and Clinical Indications
What It Is
A complete blood count (CBC) with differential is a comprehensive blood test that evaluates all cellular components of blood, including red blood cells, white blood cells with their subtypes, and platelets, providing essential diagnostic and monitoring information across virtually all medical conditions. 1
Core Components and Normal Reference Ranges
Red Blood Cell Parameters
- Hemoglobin (Hb): Measures oxygen-carrying capacity; varies by age and sex 2
- Hematocrit: Percentage of blood volume occupied by red blood cells 2
- Mean Corpuscular Volume (MCV): Average red blood cell size, useful for classifying anemia types 2
- Mean Corpuscular Hemoglobin (MCH): Average hemoglobin content per red blood cell 2
- Mean Corpuscular Hemoglobin Concentration (MCHC): Hemoglobin concentration within red blood cells 2
- Red Cell Distribution Width (RDW): Variation in red blood cell size, elevated in mixed anemias and cardiovascular disease risk 3, 2
- Reticulocyte count: Immature red blood cells, indicates bone marrow production 2
White Blood Cell Parameters
- Total white blood cell (WBC) count: Overall immune cell quantity 4
- Differential count: Breaks down WBC into specific subtypes with percentages and absolute counts 1, 5
- Neutrophils: First-line defense against bacterial infections; elevated band count >1500/mm³ has likelihood ratio of 14.5 for bacterial infection 1
- Lymphocytes: Include T cells, B cells, and NK cells; absolute count calculated by multiplying lymphocyte percentage by total WBC 6
- Monocytes: Phagocytic cells involved in chronic inflammation 5
- Eosinophils: Elevated in allergic and parasitic conditions 5
- Basophils: Least common, involved in allergic responses 5
Platelet Parameters
- Platelet count: Essential for clotting function 2
- Mean Platelet Volume (MPV): Average platelet size, elevated in cardiovascular disease 3
Critical Interpretation Guidelines
Quality Standards
- Automated differentials must achieve ≥90% lymphocyte purity (minimum 85%) within the lymphocyte gate for accurate results 6
- Both percentages and absolute counts should be reported for comprehensive assessment 6
- Results must be evaluated against laboratory-specific reference ranges that vary by age and sex 6
Key Diagnostic Ratios
- Neutrophil-to-Lymphocyte Ratio (NLR): Elevated in cardiovascular disease and metabolic syndrome 3
- Platelet-to-Lymphocyte Ratio (PLR): Predicts cardiovascular disease risk 3
- Neutrophil percentage >90%: Likelihood ratio of 7.5 for bacterial infection 1
Clinical Indications
Initial Assessment and Baseline Testing
- Required upon initiation of HIV care to detect anemia, leukopenia, and thrombocytopenia, which are common in this population 7, 1
- Essential baseline before starting myelosuppressive, nephrotoxic, or hepatotoxic medications 7
- Necessary for calculating total CD4 lymphocyte count in HIV patients 7, 1
Hematologic Malignancies
- Chronic lymphocytic leukemia diagnosis requires ≥5 × 10⁹ B lymphocytes/L (5,000/μL) in peripheral blood 6
- Acute lymphoblastic leukemia monitoring requires CBC with differential every 1-2 months during year 1, every 3 months during year 2, and every 6 months thereafter 7
- Elevated WBC in priapism may indicate underlying leukemia 1
Infection Detection
- Elevated total band count (>1500/mm³) strongly suggests bacterial infection with likelihood ratio of 14.5 1
- Left shift (band neutrophils ≥16% or total band count ≥1,500 cells/mm³) indicates acute bacterial infection 1
- WBC abnormalities without fever can still indicate underlying bacterial infections 1
Cardiovascular and Metabolic Disease Risk Assessment
- RDW, NLR, MPV, and PLR predict cardiovascular disease, arteriosclerosis, type 2 diabetes, and metabolic syndrome risk 3
Monitoring Therapeutic Response
- Tracks treatment effects in chronic myeloid leukemia 1
- Monitors for drug-induced blood dyscrasias 4
- Assesses bone marrow recovery after chemotherapy 7
Important Clinical Caveats
Limitations in Specific Conditions
- CBC is typically normal or shows only nonspecific abnormalities in valley fever (coccidioidomycosis), making it a poor diagnostic tool for this fungal infection 8
- The test lacks specificity in distinguishing bacterial from viral infections in many patients 9
- Sensitivity limitations mean normal CBC does not reliably exclude serious disease in some patients 9
Special Population Considerations
- G6PD deficiency screening is recommended before starting oxidant drugs (dapsone, primaquine, sulfonamides) in patients of African, Mediterranean, Indian, or Southeast Asian descent, as 10-15% of Black individuals carry the GdA- variant 7, 1
- Fasting glucose or HbA1c should accompany CBC in HIV patients due to increased diabetes prevalence 7