What are the diagnostic criteria and management options for polycythemia vera (PV)?

Polycythemia Vera Diagnosis and Management

The diagnosis of polycythemia vera (PV) requires the presence of JAK2 mutation (found in >95% of cases) along with elevated hemoglobin/hematocrit levels (>16.5 g/dL/49% in men or >16 g/dL/48% in women), with bone marrow examination recommended for morphologic confirmation. 1, 2

Diagnostic Criteria

Initial Evaluation

• Complete blood count with peripheral blood smear
• JAK2 V617F mutation testing (present in >95% of PV patients)
• Serum erythropoietin level (typically low in PV)
• Bone marrow examination with cytogenetic studies

Diagnostic Algorithm

1. Suspect PV when:

   • Hemoglobin/hematocrit above 95th percentile for sex and race
   • Documented increase in hemoglobin/hematocrit above patient's baseline

2. First-line testing:

   • Serum erythropoietin level interpretation:
     • Low: Probable PV
     • Normal: Possible PV
     • High: Evaluate for secondary polycythemia 3

3. Bone marrow examination:

   • Characteristic findings: hypercellularity, increased megakaryocytes with cluster formation, giant megakaryocytes, pleomorphic megakaryocyte morphology, and decreased iron stores 3
   • Cytogenetic abnormalities (found in 13-18% of patients): trisomies of chromosomes 9 and 8, deletions of chromosomes 13q and 20q 3, 2

4. Additional specialized testing (for equivocal cases):

   • Decreased megakaryocyte expression of TPO receptor (c-mpl)
   • PRV-1 gene expression in neutrophils
   • Spontaneous erythroid colony assays 3

Risk Stratification

PV patients can be categorized into risk groups based on thrombotic risk:

• High-risk: Age >60 years and/or history of thrombosis 1, 2
• Low-risk: Absence of both risk factors 2

Additional risk factors to consider:

• Leukocytosis (risk factor for thrombosis)
• High JAK2V617F allele burden (risk factor for myelofibrosis) 2

Management Approach

Core Treatment for All Patients

1. Phlebotomy:

   • Target: Maintain hematocrit <45%
   • Initial schedule: 300-500 mL every 2-3 days until target achieved 1
   • Regular monitoring to maintain target hematocrit

2. Low-dose aspirin (81-100 mg daily):

   • Recommended for all patients without contraindications
   • Particularly effective for microvascular symptoms like erythromelalgia 1, 2

High-Risk Patients

Add cytoreductive therapy:

• First-line options:
  • Hydroxyurea
  • Pegylated interferon-α (may be preferred in younger patients) 4, 2
• Second-line options:
  • Ruxolitinib (for hydroxyurea failure)
  • Busulfan 2

Symptom-Specific Management

• Pruritus (affects ~48% of patients):

  • Selective serotonin receptor antagonists 3
  • Antihistamines
  • Consider cytoreductive therapy if severe

• Erythromelalgia (affects ~3% of patients):

  • Low-dose aspirin is highly effective 1

Monitoring and Follow-up

• CBC every 2-3 months during initial management
• CBC every 3-6 months once stable
• Regular assessment for:
  • Disease progression
  • Thrombotic and bleeding complications
  • Development of post-PV myelofibrosis or acute leukemia 1

Common Pitfalls to Avoid

1. Overlooking masked PV: Expanded plasma volume can mask true erythrocytosis 1, 5

2. Excessive phlebotomy: Can lead to iron deficiency, decreased oxygen-carrying capacity, and increased stroke risk 1

3. Neglecting bone marrow examination: Essential for accurate diagnosis and baseline assessment 4

4. Overlooking secondary causes when JAK2 mutation is absent 1

5. Relying solely on hemoglobin/hematocrit: Both red cell count and hemoglobin/hematocrit should be controlled 4

6. Inadequate thrombosis prevention: Phlebotomy alone is often insufficient long-term for high-risk patients 4, 2

The long-term prognosis of PV varies significantly by age and treatment approach, with median survival of approximately 15 years overall, but exceeding 35 years for patients aged ≤40 years 2. The 20-year risks include thrombosis (~26%), post-PV myelofibrosis (16%), and acute myeloid leukemia (4%) 2.