How do you interpret a Complete Blood Count (CBC) with differential?

How to Interpret a Complete Blood Count (CBC) with Differential

A CBC with differential should be interpreted systematically by evaluating both percentages and absolute counts of all cell lines against age- and sex-specific reference ranges, with particular attention to white blood cell parameters that provide critical diagnostic information for infections, hematologic malignancies, and immune status. 1

Essential Reporting and Quality Standards

Before interpretation, ensure the results meet quality criteria:

• Results must include both percentages and absolute counts for all cell populations, as percentages alone can be misleading 2, 1
• Automated differentials should achieve at least 90% lymphocyte purity (minimum 85%) within the lymphocyte gate for accuracy 1
• The sum of CD3+CD4+ and CD3+CD8+ cells should equal total CD3+ cells within ±5% (maximum ≤10% variability) when lymphocyte subsets are measured 1
• Compare all values against laboratory-specific reference ranges that account for age and sex variations 1

Systematic Approach to Interpretation

Step 1: Evaluate White Blood Cell (WBC) Count and Differential

Start with the total WBC count and absolute neutrophil count:

• Leukocytosis (WBC ≥14,000 cells/mm³) has a likelihood ratio of 3.7 for bacterial infection, even without fever 2
• Elevated band neutrophils (≥1500 cells/mm³) have the highest diagnostic value with a likelihood ratio of 14.5 for bacterial infection 2
• Neutrophil percentage ≥90% indicates likelihood ratio of 7.5 for bacterial infection 2
• Left shift (band neutrophils or metamyelocytes ≥16%) has a likelihood ratio of 4.7 for bacterial infection 2

Critical caveat: Manual differential counting is preferred over automated methods when evaluating band forms and immature neutrophils, as this provides more accurate assessment of left shift 2

Step 2: Assess Lymphocyte Parameters

Evaluate both relative and absolute lymphocyte counts:

• Calculate absolute lymphocyte count by multiplying the lymphocyte percentage by the total WBC count 1
• In chronic lymphocytic leukemia, diagnosis requires ≥5,000 B lymphocytes/μL in peripheral blood 3
• For CLL monitoring, document both absolute lymphocyte and prolymphocyte counts, and evaluate lymphocyte doubling time 2
• Note that lymphocytes show significant circadian variation, peaking at approximately midnight (23:54) and reaching trough at mid-morning (10:47) 4

Step 3: Evaluate Red Blood Cell (RBC) Parameters

Assess the RBC indices systematically:

• Hemoglobin, RBC count, and mean corpuscular hemoglobin (MCH) are the most stable parameters 5
• Mean corpuscular volume (MCV) helps classify anemia as microcytic, normocytic, or macrocytic 6
• Red blood cell distribution width (RDW) indicates variation in RBC size 5

Important timing consideration: RBCs, hemoglobin, and hematocrit peak in morning hours 4

Step 4: Assess Platelet Count

• Evaluate absolute platelet count against reference ranges 1
• Platelets peak in late afternoon 4
• Mean platelet volume (MPV) increases with storage time after 2 days 5

Step 5: Evaluate Other WBC Populations

Assess monocytes, eosinophils, and basophils:

• Monocytes peak in late afternoon 4
• Eosinophils peak overnight 4
• Basophils peak in late afternoon 4
• These populations show higher analytical variability, particularly basophils 2

Critical Timing Considerations for Sample Processing

Perform CBC analysis within specific timeframes to ensure accuracy:

• For suspected infection, obtain CBC with differential within 12-24 hours of symptom onset (earlier if patient is seriously ill) 2
• WBC count remains stable for at least 3 days at room temperature (up to 7 days if within or above normal range) 5
• Hemoglobin, RBC count, and MCH are stable for 7 days at room temperature 5
• Platelet count is stable for at least 4 days (up to 7 days if within or above normal range) 5
• Differential parameters become unreliable after 1 day of storage, as neutrophil, lymphocyte, and eosinophil percentages artificially increase while monocyte percentages decrease 5

Understanding Analytical Variability

Recognize inherent measurement limitations:

• Automated WBC count variability: 2.2%-7.7% 2
• Manual hemocytometer WBC count variability: 9.3%-17.6% 2
• Automated lymphocyte count variability: 1.9%-5.3% 2
• Manual lymphocyte count variability: 12.5%-27% 2
• Biological variability is approximately 10% within a day and 13% within a week 2

Clinical Decision-Making Algorithm

When infection is suspected:

• If leukocytosis, left shift, or elevated bands are present → investigate thoroughly for bacterial infection even without fever 2
• If WBC is normal but neutrophil percentage ≥90% or left shift present → high likelihood of bacterial infection 2
• If no leukocytosis, no left shift, no fever, and no localized signs → additional testing may have low diagnostic yield 2

When evaluating for hematologic malignancy:

• In CLL evaluation, absolute lymphocyte count should not be the sole treatment indicator but part of overall assessment 7
• Perform unilateral bone marrow aspirate and biopsy within 2 weeks if CLL is suspected on clinical trial 7

Common pitfall: Do not rely solely on percentages—always calculate and interpret absolute counts, as a normal percentage with elevated total WBC can mask significant absolute increases in specific cell populations 2, 1