Treatment of Polycythemia Vera
Universal First-Line Therapy for All Patients
All patients with polycythemia vera require phlebotomy to maintain hematocrit strictly below 45% combined with low-dose aspirin (81-100 mg daily) unless contraindications exist. 1, 2, 3
Phlebotomy targets should be individualized: Women and African Americans may require lower hematocrit targets of approximately 42% due to physiological differences 1. The strict <45% target is based on the landmark CYTO-PV trial, which definitively demonstrated increased thrombotic risk at hematocrit levels of 45-50% 4, 1.
Low-dose aspirin significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism and should be given to all patients without contraindications 1, 2.
Aggressive cardiovascular risk factor management (particularly smoking cessation) is essential for all patients 1.
Risk Stratification Determines Need for Cytoreductive Therapy
The treatment algorithm depends on risk category:
Low-Risk Patients (Age <60 years AND no thrombosis history)
- Phlebotomy plus aspirin is generally sufficient 4, 1
- Monitor for thrombosis, bleeding, and disease progression every 3-6 months 4, 1
- Cytoreductive therapy is NOT recommended as initial treatment 4
However, cytoreductive therapy should be initiated if any of the following develop: 4
- New thrombosis or major bleeding
- Frequent phlebotomy requirement with poor tolerance
- Symptomatic or progressive splenomegaly
- Symptomatic thrombocytosis
- Progressive leukocytosis
- Progressive disease-related symptoms (pruritus, night sweats, fatigue)
High-Risk Patients (Age ≥60 years OR history of thrombosis)
Add cytoreductive therapy to phlebotomy and aspirin 1, 2, 3
Cytoreductive Agent Selection
Hydroxyurea is the first-line cytoreductive agent (starting dose 500 mg twice daily), particularly for older patients 2, 5, 6
Interferon-α is preferred for: 1, 2
- Younger patients (<40 years)
- Women of childbearing age
- Pregnant patients (starting dose 3 million units subcutaneously 3 times weekly)
Ruxolitinib (JAK2 inhibitor) is reserved for: 7, 3
- Patients resistant to or intolerant of hydroxyurea (approximately 1 in 4 patients)
- Severe protracted pruritus unresponsive to other therapies
- Marked splenomegaly not responding to hydroxyurea or interferon
Defining Hydroxyurea Resistance/Intolerance
Resistance or intolerance is defined as: 2
- Need for phlebotomy to maintain hematocrit <45% after 3 months of at least 2g/day hydroxyurea
- Uncontrolled myeloproliferation
- Failure to reduce massive splenomegaly or relieve symptoms
- Cytopenia or unacceptable side effects at any dose
Critical Safety Considerations
Avoid chlorambucil and ³²P in younger patients due to significantly increased leukemia risk 1
Perform bone marrow aspirate and biopsy before initiating cytoreductive therapy to rule out progression to myelofibrosis 4, 1
Monitor for extreme thrombocytosis (>1,500 × 10⁹/L), which may require cytoreductive therapy even in low-risk patients due to bleeding risk from acquired von Willebrand disease 1, 3
Ensure adequate fluid replacement during phlebotomy to prevent hypotension, particularly in elderly patients with cardiovascular disease 1
Symptom-Specific Management
For pruritus: 1
- Selective serotonin receptor antagonists
- Interferon-α or JAK2 inhibitors
- Antihistamines as alternative
Monitoring Strategy
Regular assessment every 3-6 months should include: 4, 1
- Monitoring for new thrombosis or bleeding
- Evaluation for signs/symptoms of disease progression
- Assessment of symptom burden
- Complete blood counts
Long-term surveillance for: 3
- Myelofibrosis transformation (12.7% of patients)
- Acute myeloid leukemia (6.8% of patients)