What are the initial lab tests for a patient suspected of having polycythemia?

Initial Laboratory Tests for Suspected Polycythemia

The initial laboratory workup for a patient suspected of having polycythemia should include complete blood count with differential, serum erythropoietin level, and JAK2 mutation testing. 1

First-Line Laboratory Tests

• Complete Blood Count (CBC) with differential

  • Confirms erythrocytosis (hemoglobin >16.5 g/dL in men, >16.0 g/dL in women)
  • Assesses other cell lines for thrombocytosis and leukocytosis
  • Includes peripheral blood smear examination 1, 2

• Serum Erythropoietin Level

  • Helps distinguish between primary (low/normal EPO) and secondary polycythemia (normal/high EPO)
  • Subnormal EPO is a minor diagnostic criterion for polycythemia vera 2, 1

• JAK2 Mutation Testing (V617F or exon 12)

  • Present in >95% of polycythemia vera cases
  • Confirms clonal nature of the disease
  • Essential for distinguishing primary from secondary causes 1, 3

Additional Initial Tests

• Iron Studies

  • Serum ferritin and transferrin saturation
  • Important to assess iron status as iron deficiency may be present in polycythemia vera 1

• Reticulocyte Count

  • Evaluates bone marrow response to erythrocytosis 1

Diagnostic Algorithm

1. If JAK2 mutation positive with elevated hemoglobin/hematocrit and low serum EPO:

   • Diagnosis of polycythemia vera is highly likely
   • Proceed to bone marrow biopsy for confirmation 2, 1

2. If JAK2 mutation negative with normal/high serum EPO:

   • Consider secondary causes of polycythemia:
     • Chronic hypoxia (sleep apnea, COPD, smoking)
     • Cyanotic heart disease
     • Renal disease/tumors
     • Androgen use 2, 1

3. If JAK2 mutation negative with low serum EPO:

   • Consider rare JAK2-negative polycythemia vera
   • Bone marrow biopsy is essential 2, 1

Bone Marrow Evaluation

While not always part of the initial workup, bone marrow aspirate and biopsy may be required for definitive diagnosis, particularly when:

• JAK2 mutation testing is negative but clinical suspicion remains high
• Distinguishing between different myeloproliferative neoplasms is necessary 2

Common Pitfalls to Avoid

• Relying solely on hemoglobin/hematocrit values without considering plasma volume status, which can lead to misdiagnosis of relative erythrocytosis
• Failing to test for JAK2 mutations when polycythemia vera is suspected
• Overlooking secondary causes of polycythemia before diagnosing polycythemia vera
• Performing repeated phlebotomies without diagnosis, which can lead to iron deficiency and increased stroke risk 1

By following this systematic approach to laboratory testing, clinicians can efficiently distinguish between primary polycythemia (polycythemia vera) and secondary causes, leading to appropriate management strategies.