What is the initial treatment for polycythemia?

Initial Treatment for Polycythemia Vera

All patients with polycythemia vera should receive therapeutic phlebotomy to maintain hematocrit strictly below 45% combined with low-dose aspirin (81-100 mg daily), regardless of risk category. 1, 2, 3

Universal First-Line Therapy

Phlebotomy

• Target hematocrit <45% in men based on the landmark CYTO-PV trial, which definitively demonstrated a 3.91-fold increased risk of cardiovascular death and major thrombosis when hematocrit was maintained at 45-50% versus <45%. 4
• Women typically require lower targets of approximately 42% due to physiological hematocrit differences. 1, 2
• Perform phlebotomy with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease. 1
• The aggressive phlebotomy approach has improved median survival to >10 years compared to <4 years historically when inadequate phlebotomy was used. 1

Aspirin Therapy

• Administer low-dose aspirin (81-100 mg daily) to all patients without contraindications, as the ECLAP study demonstrated significant reduction in cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism. 1, 2, 3
• Low-dose aspirin does not increase bleeding risk at doses of 40-100 mg. 1
• Withhold aspirin only if platelet count exceeds 1,500 × 10⁹/L due to acquired von Willebrand disease risk. 3, 5

Cardiovascular Risk Factor Management

• Mandatory smoking cessation counseling and support for all patients. 1, 6
• Aggressively manage hypertension, hyperlipidemia, and diabetes. 1, 6

Risk-Stratified Cytoreductive Therapy

High-Risk Patients (Age ≥60 years and/or history of thrombosis)

• Add cytoreductive therapy to phlebotomy and aspirin for all high-risk patients. 1, 2, 7
• Hydroxyurea is the first-line cytoreductive agent (starting dose 500 mg twice daily, titrate to 2 g/day) with Level II, A evidence. 1, 2
• Interferon-α (starting dose 3 million units subcutaneously 3 times weekly) is an alternative first-line option with Level III, B evidence, particularly preferred for younger patients (<40 years), women of childbearing age, pregnant patients, and those with intractable pruritus. 1, 2

Low-Risk Patients (Age <60 years and no thrombosis history)

• Phlebotomy and low-dose aspirin are generally sufficient without cytoreductive therapy. 1, 2
• Consider adding cytoreductive therapy if: poor tolerance of phlebotomy, need for >5 phlebotomies per year, symptomatic or progressive splenomegaly, severe disease-related symptoms, platelet count >1,500 × 10⁹/L, or progressive leukocytosis. 1, 2, 8

Critical Pitfalls to Avoid

• Never accept hematocrit targets of 45-50%, as the CYTO-PV trial definitively showed increased thrombotic risk at these levels. 1, 4
• Avoid inadequate fluid replacement during phlebotomy, which can precipitate hypotension in elderly patients with cardiovascular disease. 1
• Use hydroxyurea with caution in young patients (<40 years) due to potential leukemogenic risk with prolonged exposure. 1, 2
• Avoid chlorambucil and ³²P in younger patients due to significantly increased leukemia risk. 1
• Perform bone marrow biopsy before initiating cytoreductive therapy to rule out progression to myelofibrosis, which would alter treatment approach. 1, 6

Special Populations

Pregnant Patients

• Interferon-α is the cytoreductive agent of choice over hydroxyurea due to its safer profile. 1, 2
• Continue phlebotomy and consider low-dose aspirin if platelet count <1,500 × 10⁹/L. 5

Elderly Patients (>70 years)

• Busulfan may be considered only in this age group due to increased leukemia risk in younger patients. 1, 2

Monitoring Strategy

• Assess hematocrit levels regularly to maintain target values. 1
• Monitor for new thrombosis or bleeding events. 1
• Evaluate for signs/symptoms of disease progression every 3-6 months. 1, 6
• Assess symptom burden regularly using validated tools. 6
• No routine indication to monitor JAK2V617F allele burden except when using interferon-α therapy. 1