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 appropriate corresponding values for women), combined with low-dose aspirin. 1, 2

Risk Stratification and Treatment Algorithm

Step 1: Risk Assessment

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

Step 2: Initial Treatment for All Patients

1. Phlebotomy:

   • Target: Hematocrit <45% for men, slightly lower for women and other races
   • Induction phase: 300-450 ml blood withdrawn weekly or twice weekly until target reached
   • Maintenance phase: Same blood volume per phlebotomy, with intervals determined by hematocrit levels 1

2. Low-dose aspirin: 81-100 mg daily (if no contraindications such as bleeding risk) 1, 3

Step 3: Additional Treatment Based on Risk Category

For High-Risk Patients:

Add cytoreductive therapy:

• First-line options:
  • Hydroxyurea: Initial dose 500 mg twice daily orally 1
  • Interferon-α: Initial dose 3 million units subcutaneously 3 times weekly 1

For Low-Risk Patients:

• Phlebotomy + low-dose aspirin alone is usually sufficient 1, 3

Indications for Cytoreductive Therapy

Even in low-risk patients, cytoreductive therapy should be added if:

• Poor tolerance to phlebotomy 1
• Symptomatic or progressive splenomegaly 1
• Severe disease-related symptoms 1
• Platelet count >1,500 × 10^9/L 1, 4
• Leukocyte count >15 × 10^9/L 1
• Intractable pruritus 1

Special Considerations

Age-Based Considerations

• Older patients: Hydroxyurea or busulfan (initial dose 4 mg/day) are preferred 1
• Younger patients: Consider interferon-α due to theoretical concerns about leukemogenicity of hydroxyurea, though evidence for this risk is limited 1
• Women of childbearing age: Interferon-α is preferred due to potential teratogenicity of other agents 1, 4

Managing Side Effects

• Hydroxyurea: Monitor for neutropenia, mucocutaneous changes, and leg ulcers 1
• Interferon-α: Common side effects include flu-like symptoms, fatigue, and weight loss 1
• Busulfan: Watch for pulmonary fibrosis and bone marrow aplasia 1

Monitoring Response

• Regular blood counts to maintain target hematocrit
• Assess symptom improvement
• Monitor for disease progression to myelofibrosis or leukemia 3

Clinical Pitfalls to Avoid

1. Inadequate hematocrit control: The CYTO-PV trial demonstrated a 4-fold increase in cardiovascular events when hematocrit was maintained at 45-50% versus <45% 1

2. Overlooking iron deficiency: While iron supplementation may be needed for symptomatic iron deficiency (pica, mouth paresthesia), be cautious as it may worsen erythrocytosis 1

3. Neglecting cardiovascular risk factors: Aggressive management of cardiovascular risk factors is essential 1

4. Excessive phlebotomy: In patients requiring frequent phlebotomies, consider adding cytoreductive therapy rather than continuing aggressive phlebotomy alone 5

The evidence strongly supports that maintaining hematocrit below 45% through phlebotomy, combined with low-dose aspirin and appropriate cytoreductive therapy based on risk stratification, is the most effective approach to reduce morbidity and mortality in polycythemia vera patients 1, 3.