What is the initial treatment for polycythemia?

Initial Treatment for Polycythemia Vera

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

Risk Stratification First

Before initiating treatment, classify patients into risk categories:

• Low-risk: Age <60 years AND no history of thrombosis 1
• High-risk: Age ≥60 years OR history of thrombosis 1, 3

Universal Initial Treatment (All Patients)

Phlebotomy

• Target hematocrit strictly <45% in men, with corresponding lower values for women (approximately 42%) and African Americans due to physiological differences 1, 2
• The CYTO-PV trial definitively demonstrated that hematocrit targets of 45-50% carry significantly increased thrombotic risk 1
• Perform phlebotomy 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

• Administer 81-100 mg daily to all patients without contraindications 1, 2, 3
• Aspirin significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism 1
• Aspirin is particularly effective for microvascular symptoms including erythromelalgia and headaches 4, 5

Cardiovascular Risk Factor Management

• Aggressively manage modifiable risk factors, especially smoking cessation 1

Treatment Based on Risk Category

Low-Risk Patients

• Phlebotomy plus low-dose aspirin is generally sufficient 1, 2
• No cytoreductive therapy needed initially 1

High-Risk Patients

• Add cytoreductive therapy to phlebotomy and aspirin 1, 2, 3
• Consider bone marrow aspirate and biopsy to rule out disease progression to myelofibrosis prior to initiating cytoreductive therapy 1

First-Line Cytoreductive Options:

Hydroxyurea (preferred for older patients >40 years):

• Starting dose: 500 mg twice daily 2
• Level II, A evidence from the European Society for Medical Oncology 1
• Effective in controlling proliferative phase of PV 5, 6

Interferon-α (preferred for younger patients <40 years and women of childbearing age):

• Starting dose: 3 million units subcutaneously 3 times weekly 2
• Level III, B evidence 1
• Non-leukemogenic alternative 5
• Particularly useful in pregnant patients 1

Additional Indications for Cytoreductive Therapy

Beyond high-risk status, consider cytoreductive therapy for:

• Poor tolerance of phlebotomy or frequent phlebotomy requirement 2
• Symptomatic or progressive splenomegaly 2
• Severe disease-related symptoms 2
• Extreme thrombocytosis (platelet count >1,500 × 10⁹/L) due to bleeding risk from acquired von Willebrand disease 1, 3
• Progressive leukocytosis 2

Critical Pitfalls to Avoid

• Never accept hematocrit targets of 45-50%—this significantly increases thrombotic risk 1
• Avoid chlorambucil and ³²P in younger patients due to significantly increased leukemia risk 1
• Do not use phlebotomy for relative polycythemia—it is contraindicated in this condition 7
• Avoid inadequate fluid replacement during phlebotomy, which can precipitate hypotension in elderly or cardiovascular disease patients 1

Monitoring

• Evaluate for new thrombosis or bleeding every 3-6 months 1
• Assess symptom burden regularly 1
• Monitor for signs/symptoms of disease progression to myelofibrosis 1