How do you interpret an abnormal Complete Blood Count (CBC) with differential results?

Interpreting CBC with Differential: A Systematic Approach

To interpret an abnormal CBC with differential, systematically evaluate each cell line (red cells, white cells, platelets) using both absolute counts and indices, then correlate findings with clinical context to generate a focused differential diagnosis. 1

Step 1: Evaluate Red Blood Cell Parameters

Assess hemoglobin, hematocrit, and MCV first to determine if anemia, polycythemia, or dehydration is present. 1

• Hemoglobin/Hematocrit: Low values indicate anemia; elevated values suggest polycythemia or hemoconcentration 1

• MCV Classification: Use MCV to categorize anemia as:

  • Microcytic (MCV <80 fL): Consider iron deficiency, thalassemia, chronic disease 1
  • Normocytic (MCV 80-100 fL): Consider acute blood loss, hemolysis, bone marrow suppression 1
  • Macrocytic (MCV >100 fL): Consider B12/folate deficiency, liver disease, hypothyroidism 1

• Reticulocyte Count: A low reticulocyte index indicates decreased RBC production (bone marrow failure, nutritional deficiency), while elevated counts suggest blood loss or hemolysis 1, 2

Common pitfall: MCHC is the most important calculated index for detecting spurious results—abnormal MCHC should prompt verification of other parameters 3

Step 2: Analyze White Blood Cell Count and Differential

Evaluate total WBC count and absolute counts of each cell type (not just percentages), as this provides the most clinically relevant information. 1

Neutrophils

• Neutrophilia with left shift (band count >1,500 cells/mm³) strongly indicates bacterial infection with a likelihood ratio of 14.5 1
• Neutropenia (<1,500 cells/mm³): Consider bone marrow suppression, autoimmune destruction, overwhelming infection 2

Lymphocytes

• Lymphocytosis: Typically indicates viral infection, chronic lymphocytic leukemia, or pertussis 1
• Lymphopenia (<1,000 cells/mm³): Consider HIV, immunosuppressive therapy, malnutrition, or autoimmune disease 2

Eosinophils

• Eosinophilia: Suggests allergic conditions, parasitic infections, or drug reactions 1

Other Considerations

• Always report both percentages AND absolute counts for accurate interpretation 1
• Do not rely solely on WBC to distinguish bacterial from viral infection—the test lacks specificity in many patients 4

Critical pitfall: Do not overlook left shift even when total WBC is normal—this can still indicate significant bacterial infection 1

Step 3: Assess Platelet Count

Evaluate platelet count for thrombocytopenia or thrombocytosis. 1

• Thrombocytopenia (<150,000/μL): Consider immune destruction (ITP), bone marrow suppression, consumption (DIC), sequestration (hypersplenism) 2, 1
• Thrombocytosis (>450,000/μL): Consider reactive causes (infection, inflammation, iron deficiency) versus primary myeloproliferative disorders 1

For immune thrombocytopenia workup: Obtain peripheral smear, reticulocyte count, and test for HIV, hepatitis B/C, and H. pylori 2

Step 4: Identify Spurious Results

Check for technical artifacts that can falsely alter CBC values. 3

• Spuriously low WBC: EDTA-induced agglutination, clotting 3
• Spuriously high WBC: Nucleated RBCs, platelet clumps, cryoglobulins, lipemia 3
• Spuriously abnormal hemoglobin/RBC: Lipemia, cold agglutinins, extreme hyperglycemia, markedly elevated WBC 3
• Spuriously abnormal MCV: Cold agglutinins, hyperglycemia, prolonged storage 3

Key indicator of spurious results: Abnormal MCHC (>37 g/dL or <30 g/dL) should trigger verification 3

Step 5: Generate Differential Diagnosis Based on Pattern

Pancytopenia (all three cell lines decreased)

• Bone marrow failure (aplastic anemia, myelodysplasia) 2
• Bone marrow infiltration (leukemia, metastatic cancer) 2
• Hypersplenism 2
• Nutritional deficiencies (B12, folate) 2

Isolated Cytopenias

• Anemia alone: Iron deficiency, chronic disease, hemolysis, blood loss 1, 5
• Leukopenia alone: Viral infection, drug effect, autoimmune 2
• Thrombocytopenia alone: ITP, drug-induced, viral infection 2

Elevated Cell Lines

• Leukocytosis: Infection, inflammation, leukemia, corticosteroids 1, 5
• Polycythemia: Dehydration, chronic hypoxia, polycythemia vera 1

Step 6: Determine Need for Further Testing

If new cytopenia develops or worsens, repeat CBC within 2-4 weeks. 6

• If abnormalities persist over 2+ measurements, proceed to bone marrow evaluation rather than continued monitoring 6
• For suspected acute processes, repeat CBC within 1 week 6
• Do not order additional tests if results will not change management 1

When to Perform Bone Marrow Evaluation

• Unexplained pancytopenia 2
• Persistent isolated cytopenia after repeat testing 6
• Concern for aplastic anemia (hypocellular marrow <25% with ANC <500, platelets <20,000, reticulocytes <20,000) 2
• Suspected hematologic malignancy 2

Critical consideration: The CBC is helpful for diagnosing anemia, infection, malignancy, and monitoring drug effects, but has limitations in distinguishing bacterial from viral infections due to lack of specificity. 5, 4