What is the initial treatment for Polycythemia Vera (PV)?

Initial Treatment for Polycythemia Vera

All patients with polycythemia vera should receive therapeutic phlebotomy to maintain hematocrit strictly below 45% and low-dose aspirin (81-100 mg daily), with cytoreductive therapy added for high-risk patients (age >60 years or history of thrombosis). 1, 2

Universal First-Line Therapy (All Patients)

Phlebotomy

• Maintain hematocrit strictly below 45% in all patients regardless of sex or risk category 1, 2
• The CYTO-PV trial definitively demonstrated that hematocrit targets of 45-50% result in significantly increased thrombotic events compared to <45% 1, 2
• Consider lower targets of approximately 42% for women due to physiological differences in normal hematocrit ranges 1, 2, 3
• Perform phlebotomy with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease 2, 3

Low-Dose Aspirin

• Administer 81-100 mg daily to all patients without contraindications 1, 2
• The ECLAP study demonstrated that aspirin significantly reduces cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major venous thromboembolism 1, 2

Cardiovascular Risk Factor Management

• Aggressively manage all modifiable risk factors including hypertension, hyperlipidemia, and diabetes 1, 2
• Mandatory smoking cessation counseling and support 1, 2

Risk Stratification

Low-Risk Patients (Age <60 Years AND No Thrombosis History)

• Phlebotomy plus aspirin alone is sufficient as initial treatment 1, 2
• Cytoreductive therapy is not recommended as initial treatment for this group 1, 2

High-Risk Patients (Age ≥60 Years OR History of Thrombosis)

• Add cytoreductive therapy to phlebotomy and aspirin 1, 2

Cytoreductive Therapy Selection (High-Risk Patients Only)

First-Line Cytoreductive Options

Hydroxyurea (preferred for most high-risk patients):

• Recommended with Level II, A evidence by the European LeukemiaNet 1, 2
• Well-established efficacy and tolerability in the majority of patients 1, 2
• Use with caution in patients <40 years due to potential leukemogenic risk with prolonged exposure 1, 2
• Starting dose typically 500 mg twice daily 4

Interferon-α (preferred for specific populations):

• Recommended with Level III, B evidence by the European LeukemiaNet 1, 2
• Preferred first-line agent for: 1, 2
  • Younger patients (age <40 years)
  • Women of childbearing age
  • Pregnant patients requiring cytoreductive therapy
  • Patients with refractory pruritus
• Achieves up to 80% hematologic response rate and is non-leukemogenic 2
• Can reduce JAK2V617F allelic burden 1, 2
• Starting dose typically 3 million units subcutaneously 3 times weekly 4

Additional Indications for Cytoreductive Therapy

Beyond age and thrombosis history, consider cytoreductive therapy for: 2, 4

• Poor tolerance of phlebotomy or frequent phlebotomy requirement
• Symptomatic or progressive splenomegaly
• Severe disease-related symptoms
• Platelet count >1,500 × 10⁹/L (extreme thrombocytosis with bleeding risk)
• Progressive leukocytosis

Common Pitfalls to Avoid

• Do not accept hematocrit targets of 45-50% - the CYTO-PV trial definitively showed increased thrombotic risk at these levels 2
• Avoid chlorambucil and ³²P in younger patients - these agents carry significantly increased leukemia risk 2
• Do not use hydroxyurea as first-line in pregnant patients - interferon-α is the cytoreductive agent of choice in pregnancy 1, 2
• Avoid inadequate fluid replacement during phlebotomy - can precipitate hypotension, particularly in elderly patients with cardiovascular disease 2, 3

Monitoring

• Monitor hematocrit levels regularly to maintain target values 2, 3
• Evaluate for new thrombosis or bleeding events 2
• Assess for signs/symptoms of disease progression every 3-6 months 2
• Consider bone marrow aspirate and biopsy to rule out progression to myelofibrosis prior to initiating cytoreductive therapy 2