What is a good workup for pancytopenia?

Comprehensive Workup for Pancytopenia

A comprehensive pancytopenia workup should include complete blood count with differential, peripheral blood smear examination, bone marrow aspiration and biopsy, and targeted laboratory tests to identify the underlying cause. 1

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with differential - Confirm pancytopenia and assess severity of each cell line deficiency 1
• Peripheral Blood Smear Examination - Evaluate for:
  • Cell morphology abnormalities (macrocytosis, microcytosis, hypersegmented neutrophils)
  • Presence of blasts or abnormal cells
  • Platelet size and morphology
  • Red cell abnormalities (tear drops, target cells, nucleated RBCs) 2, 1
• Reticulocyte Count - Differentiates between production vs. destruction/sequestration causes 1
• Comprehensive Metabolic Panel - Assess liver and kidney function 1

Specialized Laboratory Tests

• Vitamin and Nutritional Studies:

  • Vitamin B12 and folate levels
  • Serum ferritin, transferrin, and transferrin saturation 2
  • Copper levels (if suspected deficiency)

• Infectious Disease Workup:

  • HIV testing
  • Hepatitis panel (B and C)
  • EBV, CMV, parvovirus B19 serology
  • Blood cultures if febrile 1

• Autoimmune Evaluation:

  • ANA, anti-dsDNA
  • Rheumatoid factor
  • Direct Coombs test (if hemolysis suspected)

• Additional Specialized Tests:

  • Serum protein electrophoresis and immunofixation
  • Serum free light chains (if multiple myeloma suspected) 2
  • Flow cytometry of peripheral blood (if leukemia/lymphoma suspected)
  • Paroxysmal nocturnal hemoglobinuria (PNH) testing 2
  • LDH and haptoglobin (if hemolysis suspected) 2

Bone Marrow Evaluation

• Bone Marrow Aspiration and Biopsy - Should be performed simultaneously as they are complementary 3, 4

  • Aspirate for:
    • Cytomorphology assessment
    • Flow cytometry
    • Cytogenetics
    • Molecular studies
  • Biopsy for:
    • Cellularity assessment
    • Fibrosis evaluation
    • Architecture assessment
    • CD138 staining (if plasma cell disorder suspected) 2

• Special Stains and Studies:

  • Iron stain (Prussian blue/Perls stain)
  • Reticulin stain (for fibrosis)
  • PAS and MPO stains (for leukemia evaluation) 3
  • Immunohistochemistry for specific markers

• Cytogenetic Studies:

  • Standard metaphase cytogenetics
  • FISH for specific abnormalities (especially if MDS or leukemia suspected) 2
  • Next-generation sequencing for molecular mutations 5

Imaging Studies

• Chest X-ray - Evaluate for infections, malignancies
• Abdominal Ultrasound - Assess spleen size (hypersplenism) and liver pathology
• CT scan - If lymphoma or solid malignancy suspected
• MRI - If bone marrow infiltration suspected (e.g., multiple myeloma) 2

Common Pitfalls to Avoid

1. Failing to perform both bone marrow aspiration and biopsy - Studies show that both procedures are complementary and should be performed simultaneously for complete evaluation 3, 4

2. Missing megaloblastic anemia - This is a common and readily treatable cause of pancytopenia that should not be overlooked 4, 6

3. Attributing pancytopenia to medications without excluding other causes - While drug-induced pancytopenia is common, other serious etiologies must be ruled out 1

4. Overlooking infections - Recent studies show infections are a leading cause of pancytopenia in some populations 7

5. Delaying hematology referral - Patients with unexplained cytopenias should be promptly referred to hematology for evaluation 1

Most Common Etiologies to Consider

1. Aplastic anemia - Most common cause in many studies 3, 4
2. Megaloblastic anemia (B12/folate deficiency) - Rapidly correctable and should not be missed 4, 6
3. Myelodysplastic syndromes - Especially in older adults 2
4. Acute leukemias - Require urgent diagnosis and treatment 2
5. Hypersplenism - Consider in patients with splenomegaly 4, 7
6. Infections - Particularly in developing countries 7
7. Bone marrow infiltration - From malignancies or storage diseases 1

The diagnostic approach to pancytopenia requires systematic evaluation with attention to clinical presentation, laboratory findings, and bone marrow examination. Early diagnosis and identification of the underlying cause are crucial for appropriate management and improved outcomes.