What is the initial treatment for polycythemia?

Initial Treatment for Polycythemia Vera

The mainstay of therapy for all patients with polycythemia vera is phlebotomy to maintain hematocrit below 45% in men (and approximately 42% in women), combined with low-dose aspirin (81-100 mg/day) for all patients without contraindications. 1

Risk Stratification and Treatment Algorithm

Step 1: Risk Assessment

Patients should be stratified into risk categories to guide treatment:

• Low-risk: Age <60 years AND no history of thrombosis
• High-risk: Age ≥60 years OR history of thrombosis

Step 2: Initial Treatment Based on Risk

For ALL Patients (regardless of risk):

• Phlebotomy to maintain hematocrit <45% in men and <42% in women 1
  • This target is based on the CYTO-PV trial which demonstrated that maintaining hematocrit <45% significantly reduced cardiovascular death and major thrombosis compared to a target of 45-50% 2
• Low-dose aspirin (81-100 mg/day) if no contraindications 1
• Management of cardiovascular risk factors (smoking cessation, blood pressure control, etc.)

Additional Treatment for High-Risk Patients:

• Cytoreductive therapy should be initiated 1
  • First-line: Hydroxyurea (starting dose: 500 mg twice daily) 1
  • Alternative (especially for younger patients or pregnant women): Interferon-α (3 million units subcutaneously 3 times weekly) 1

Special Considerations

When to Add Cytoreductive Therapy in Low-Risk Patients

Consider adding cytoreductive therapy if any of the following develop 1:

• New thrombosis or major bleeding
• Poor tolerance to phlebotomy with frequent/persistent need
• Symptomatic or progressive splenomegaly
• Symptomatic thrombocytosis
• Progressive leukocytosis
• Progressive disease-related symptoms (pruritus, night sweats, fatigue)

Age-Specific Considerations

• Younger patients: Consider interferon-α as first-line cytoreductive therapy due to theoretical concerns about leukemogenicity with long-term hydroxyurea exposure 1
• Older patients: Hydroxyurea is generally preferred due to better tolerability and ease of administration 1

Pregnancy

• For pregnant women requiring cytoreductive therapy, interferon-α is the preferred agent as it does not cross the placenta 1, 3

Monitoring and Follow-up

• Monitor hematocrit, complete blood count, and symptoms every 3-6 months 1
• Perform bone marrow biopsy if there are signs of disease progression before changing cytoreductive therapy 1

Common Pitfalls to Avoid

1. Inadequate phlebotomy: Failing to maintain hematocrit <45% increases thrombotic risk significantly 2
2. Overaggressive phlebotomy: Perform phlebotomy with careful monitoring and appropriate fluid replacement to avoid hypotension or fluid overload, especially in patients with cardiovascular disease 1
3. Ignoring symptoms: Disease-related symptoms like pruritus, night sweats, and fatigue should prompt consideration of cytoreductive therapy even in low-risk patients 1
4. Neglecting aspirin contraindications: Avoid aspirin in patients with extreme thrombocytosis (>1,500 × 10^9/L) due to increased bleeding risk 3, 4

The evidence strongly supports that proper control of hematocrit below 45% through phlebotomy is essential for reducing mortality and morbidity in polycythemia vera patients, with the addition of cytoreductive therapy for high-risk patients or those with progressive symptoms.