What is the initial step in a polycythemia (excessive red blood cell count) work-up?

Initial Work-up for Polycythemia

The initial step in a polycythemia work-up should include complete blood count (CBC) with peripheral blood smear, JAK2 V617F mutation testing, and serum erythropoietin level. 1

Diagnostic Approach for Suspected Polycythemia

First-line Testing

1. Complete blood count (CBC) with peripheral blood smear

   • Confirm elevated hemoglobin/hematocrit above the 95th percentile adjusted for sex and race
   • Look for associated thrombocytosis or leukocytosis which may suggest polycythemia vera (PV)

2. JAK2 V617F mutation testing

   • Present in >95% of PV cases 2
   • Helps distinguish primary from secondary polycythemia

3. Serum erythropoietin level

   • Low or subnormal in PV (a minor diagnostic criterion) 1
   • Elevated in secondary polycythemia 3

Interpretation of Initial Results

• If JAK2 mutation positive + low/normal erythropoietin: Strongly suggests polycythemia vera
• If JAK2 mutation negative + elevated erythropoietin: Consider secondary causes
• If JAK2 mutation negative + normal/low erythropoietin: Consider rare JAK2-negative PV or other myeloproliferative disorders

Secondary Causes to Consider

When evaluating polycythemia, it's essential to rule out secondary causes:

• Chronic hypoxia (COPD, sleep apnea)
• Smoking
• High altitude exposure
• Cyanotic heart disease
• Renal disease or renal transplant
• Androgen use 1

Additional Testing When Indicated

• Bone marrow biopsy: Required for definitive diagnosis of PV according to WHO criteria

  • Look for hypercellularity, increased megakaryocytes with cluster formation, and decreased iron stores 1
  • May not be needed initially if JAK2 mutation and other criteria are clearly positive 4

• Additional genetic testing: If JAK2 V617F is negative but PV still suspected, test for other functionally similar JAK2 mutations 1

Common Pitfalls to Avoid

1. Failing to check erythropoietin level: This is crucial for differentiating between primary and secondary polycythemia 3

2. Overlooking JAK2 testing: Nearly all PV cases (>95%) have JAK2 mutations 2

3. Premature phlebotomy: Starting treatment before establishing diagnosis may mask true hemoglobin/hematocrit levels and complicate diagnosis 1

4. Ignoring secondary causes: Always evaluate for common secondary causes before concluding primary polycythemia 5

5. Missing iron deficiency: Iron deficiency from repeated phlebotomies can mask true hemoglobin/hematocrit levels in PV patients 1

By following this systematic approach with appropriate initial testing (CBC, JAK2 mutation, and erythropoietin level), clinicians can efficiently differentiate between polycythemia vera and secondary causes, leading to appropriate management strategies.