What is the initial treatment for polycythemia (excessive red blood cell count)?

Initial Treatment for Polycythemia Vera

Phlebotomy to maintain hematocrit below 45% is the cornerstone of initial treatment for all patients with polycythemia vera, combined with low-dose aspirin (81-100 mg daily) unless contraindicated. 1, 2

Risk Stratification Determines Treatment Intensity

Before initiating therapy, patients must be stratified into risk categories that guide treatment decisions 1:

• Low-risk patients: Age <60 years AND no history of thrombosis 1
• High-risk patients: Age ≥60 years OR history of thrombosis 1

Universal First-Line Treatment Components

Phlebotomy

• Target hematocrit <45% based on the definitive CYTO-PV trial, which demonstrated increased thrombotic risk at higher levels 1, 2
• Women and African Americans may require lower targets (approximately 42%) due to physiological differences 1
• Perform with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease 1
• This aggressive approach has improved median survival to >10 years compared to <4 years historically 1

Low-Dose Aspirin

• 81-100 mg daily for all patients without contraindications 1, 2
• Significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism 1
• Particularly effective for aspirin-responsive microvascular symptoms including erythromelalgia and headaches 3, 4

Cardiovascular Risk Factor Management

• Aggressive management including smoking cessation is essential 1

Treatment Based on Risk Category

Low-Risk Patients

Phlebotomy plus low-dose aspirin is generally sufficient without cytoreductive therapy 1

High-Risk Patients

Add cytoreductive therapy to phlebotomy and aspirin 1, 2:

First-line cytoreductive options:

• Hydroxyurea: First-line option with level II, A evidence 1

  • Initial dosage: 500 mg twice daily 3
  • Achieves control of hematocrit and platelet count within 12 weeks in >80% of patients 5
  • Monitor for neutropenia and mucocutaneous changes 3

• Interferon-α: First-line option with level III, B evidence 1

  • Initial dosage: 3 million units subcutaneously 3 times weekly 3
  • Preferred for younger patients due to concerns about long-term leukemogenicity with hydroxyurea, though no hard evidence supports this concern 3
  • Mandatory for women of childbearing age due to theoretical teratogenicity of other agents 3, 1
  • Preferred for intractable pruritus 3

Avoid in younger patients:

• Chlorambucil and radioactive phosphorus (³²P) carry significantly increased leukemia risk 1

Special Considerations

Extreme Thrombocytosis

• Consider cytoreductive therapy for platelet counts >1500 × 10⁹/L due to acquired von Willebrand disease and bleeding risk 1, 2

Symptom Management

• Pruritus: Selective serotonin receptor antagonists, interferon-α, JAK2 inhibitors, or antihistamines 1
• Erythromelalgia: Low-dose aspirin is highly effective 3, 4

Critical Pitfalls to Avoid

• Do not accept hematocrit targets of 45-50%: The CYTO-PV trial definitively showed increased thrombotic risk at these levels 1
• Avoid phlebotomy alone in relative polycythemia: Phlebotomy is contraindicated in relative (spurious) polycythemia 6
• Do not perform inadequate fluid replacement during phlebotomy: Can precipitate hypotension in elderly patients with cardiovascular disease 1
• Avoid excessive aspirin use: Only low-dose aspirin (81-100 mg) is indicated 3

Monitoring Requirements

• Evaluate for new thrombosis or bleeding every 3-6 months 1
• Assess symptom burden regularly 1
• Consider bone marrow aspirate and biopsy to rule out progression to myelofibrosis prior to initiating cytoreductive therapy 1
• Monitor for disease transformation: 12.7% develop myelofibrosis and 6.8% develop acute myeloid leukemia 2