What laboratory tests should be ordered for a patient with pancytopenia?

Laboratory Workup for Patients with Pancytopenia

For patients with pancytopenia, a comprehensive laboratory workup should include complete blood count with differential, peripheral blood smear, bone marrow aspiration and biopsy, and targeted testing for common etiologies including vitamin deficiencies, infections, and malignancies.

Initial Laboratory Evaluation

• Complete Blood Count (CBC) with differential 1

  • Confirms the presence and severity of pancytopenia
  • Evaluates the degree of anemia, leukopenia, and thrombocytopenia
  • Provides information on cell morphology (e.g., macrocytosis)

• Peripheral Blood Smear 1, 2

  • Essential first-line test to evaluate:
    • Red cell morphology (macrocytosis, microcytosis, anisocytosis)
    • White cell morphology (dysplastic changes, toxic granulation)
    • Platelet size and morphology
    • Presence of abnormal cells suggesting malignancy

• Reticulocyte Count 1, 3

  • Helps distinguish between bone marrow production problems (low count) and peripheral destruction (high count)
  • Most patients with pancytopenia have counts in the 0.1-2% range 4

Bone Marrow Studies

• Bone Marrow Aspiration and Biopsy 1, 4
  • Critical diagnostic test for pancytopenia
  • Evaluates:
    • Cellularity (hypocellular, normocellular, hypercellular)
    • Dysplastic changes
    • Presence of abnormal cells or infiltrates
    • Iron stores (Prussian blue stain)
  • Both aspiration and biopsy should be performed simultaneously as aspiration alone may be inadequate 5

Nutritional and Vitamin Studies

• Vitamin B12 and Folate Levels 1, 2

  • Essential as megaloblastic anemia is a major reversible cause of pancytopenia 5, 6
  • Vitamin B12 deficiency can cause severe pancytopenia with hemolysis 7

• Iron Studies 1

  • Serum ferritin
  • Serum iron
  • Total iron binding capacity
  • Transferrin saturation

Immunologic and Infectious Disease Testing

• Autoimmune Markers 2

  • Antinuclear antibodies (ANA)
  • Antiphospholipid antibodies
  • Direct antiglobulin test (Coombs test) to evaluate for immune-mediated hemolysis

• Infectious Disease Testing 2, 3

  • HIV testing
  • Hepatitis screening (B and C)
  • Testing for other infections based on clinical suspicion (e.g., enteric fever, dengue)

Additional Tests Based on Clinical Suspicion

• Liver Function Tests 1

  • To evaluate for liver disease which may cause pancytopenia through hypersplenism

• Serum Lactate Dehydrogenase (LDH) 1

  • Elevated in hemolysis and certain malignancies

• Abdominal Ultrasound 2

  • To assess spleen size and liver morphology
  • Particularly important if hypersplenism is suspected

• Flow Cytometry 1

  • For suspected hematologic malignancies
  • To evaluate for paroxysmal nocturnal hemoglobinuria (PNH)

• Cytogenetic Studies 1

  • For suspected myelodysplastic syndromes or leukemia
  • Conventional karyotyping
  • FISH for specific abnormalities

• Molecular Testing 1

  • Next-generation sequencing for clonal markers in suspected myeloid neoplasms

Common Pitfalls to Avoid

1. Failing to perform both bone marrow aspiration and biopsy - Aspiration alone may be unsuccessful in obtaining adequate samples 5

2. Missing vitamin B12 deficiency - A rapidly correctable cause of pancytopenia that can present acutely in critically ill patients 5

3. Overlooking peripheral destruction causes - Not all pancytopenia is due to bone marrow failure; hypersplenism and immune-mediated destruction are important considerations 3

4. Neglecting to evaluate for infections - Infections are a leading cause of pancytopenia in many populations 3

5. Focusing only on malignant causes - While important to exclude, many cases of pancytopenia are due to reversible causes such as nutritional deficiencies and infections 6, 3

The diagnostic approach should be systematic and thorough, as pancytopenia represents a wide array of disorders ranging from easily treatable conditions to life-threatening diseases requiring urgent intervention.