What lab tests are needed to diagnose polycythemia?

Laboratory Tests for Diagnosing Polycythemia

The essential laboratory tests for diagnosing polycythemia include complete blood count with peripheral blood smear, serum erythropoietin level, and JAK2 mutation testing, with bone marrow examination indicated in equivocal cases. 1

Initial Laboratory Evaluation

First-line Tests

• Complete blood count (CBC) with peripheral blood smear

  • Look for elevated hemoglobin (>16.5 g/dL in men, >16.0 g/dL in women) 2
  • Check for associated thrombocytosis and leukocytosis
  • Examine peripheral smear for morphologic abnormalities

• Serum erythropoietin (EPO) level

  • A low EPO level has >90% specificity for polycythemia vera (PV) 1
  • Normal or high EPO suggests secondary polycythemia

• JAK2 mutation testing

  • JAK2 V617F mutation (present in ~97% of PV cases) 1
  • JAK2 exon 12 mutation testing if V617F is negative but PV still suspected 3

Second-line Tests

• Bone marrow examination with cytogenetic studies

  • Indicated to confirm diagnosis in equivocal cases
  • Shows hypercellularity, increased megakaryocytes with cluster formation, giant megakaryocytes, and pleomorphism 1
  • Helps identify reticulin fibrosis and decreased iron deposits
  • Abnormal karyotype is seen in 15-20% of patients 4

• Additional molecular testing (when indicated)

  • Testing for other mutations (TET2, ASXL1, SRSF2, IDH2, RUNX1, U2AF1) may help with prognosis 4

Tests for Secondary Causes

If JAK2 mutation is absent or EPO level is normal/elevated, investigate for secondary causes:

• Arterial blood gas to assess oxygen saturation
• Pulmonary function tests for hypoxic lung disease
• Sleep study if sleep apnea suspected
• Abdominal imaging (ultrasound or CT) to evaluate for renal or hepatic tumors
• Carboxyhemoglobin level if smoker's polycythemia suspected

Diagnostic Algorithm

1. Initial screening: CBC with peripheral smear and clinical assessment
2. If elevated hemoglobin/hematocrit:
   • JAK2 mutation testing and serum EPO level simultaneously
3. Interpret results:
   • JAK2 positive + low EPO = PV highly likely
   • JAK2 negative + low EPO = consider JAK2 exon 12 testing and bone marrow biopsy
   • JAK2 negative + normal/high EPO = investigate secondary causes

Common Pitfalls to Avoid

• Overlooking relative polycythemia caused by dehydration, diuretics use, or smoker's polycythemia 1
• Unnecessary red cell mass measurements are rarely needed with modern diagnostic approaches 1
• Missing secondary causes of polycythemia, especially in JAK2-negative cases 1
• Relying solely on hemoglobin/hematocrit levels without considering that 5.99% of men and 0.22% of women with normal CBC may have values above the WHO diagnostic thresholds 5

Remember that a diagnosis of PV requires either both major criteria (elevated hemoglobin/hematocrit and presence of JAK2 mutation) plus at least one minor criterion, or the first major criterion plus at least two minor criteria according to the revised WHO classification 3.