What is the initial treatment for Polycythemia Vera (PV)?

Initial Treatment for Polycythemia Vera

All patients with polycythemia vera should receive therapeutic phlebotomy to maintain hematocrit strictly below 45% and low-dose aspirin (81-100 mg daily), with cytoreductive therapy added for high-risk patients (age >60 years or history of thrombosis). 1, 2

Universal First-Line Therapy (All Patients)

Phlebotomy

• Maintain hematocrit strictly below 45% in all patients regardless of sex or risk category 1, 2
• The CYTO-PV trial definitively demonstrated that hematocrit targets of 45-50% result in significantly increased thrombotic events compared to <45% 1, 2
• Consider lower targets of approximately 42% for women due to physiological differences in normal hematocrit ranges 1, 2, 3
• Perform phlebotomy with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease 2, 3

Low-Dose Aspirin

• Administer 81-100 mg daily to all patients without contraindications 1, 2
• The ECLAP study demonstrated that aspirin significantly reduces cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major venous thromboembolism 1, 2

Cardiovascular Risk Factor Management

• Aggressively manage all modifiable risk factors including hypertension, hyperlipidemia, and diabetes 1, 2
• Mandatory smoking cessation counseling and support 1, 2

Risk Stratification

Low-Risk Patients (Age <60 Years AND No Thrombosis History)

• Phlebotomy plus aspirin alone is sufficient as initial treatment 1, 2
• Cytoreductive therapy is not recommended as initial treatment 1

High-Risk Patients (Age ≥60 Years OR History of Thrombosis)

• Add cytoreductive therapy to phlebotomy and aspirin 1, 2

Cytoreductive Therapy Selection (High-Risk Patients Only)

First-Line Cytoreductive Options

Hydroxyurea (Level II, A evidence):

• Recommended as first-line for most high-risk patients, particularly those >40 years old 1, 2, 4
• Starting dose: 500 mg twice daily, titrated to maintain hematocrit <45% and control blood counts 4
• Caution in young patients (<40 years) due to potential leukemogenic risk with prolonged exposure 1, 2
• The pipobroman comparison trial showed lower leukemia rates with hydroxyurea (24% vs 52% at 20 years) 1

Interferon-α (Level III, B evidence):

• Preferred for patients <40 years old 1, 2, 4
• Preferred for women of childbearing age and pregnant patients requiring cytoreductive therapy 1, 2, 4
• Starting dose: 3 million units subcutaneously 3 times weekly 4
• Achieves up to 80% hematologic response rate and is non-leukemogenic 2
• Particularly effective for refractory pruritus 1, 2
• Can reduce JAK2V617F allelic burden 2

Additional Indications for Cytoreductive Therapy

Beyond age/thrombosis risk, consider cytoreductive therapy for:

• Poor tolerance or frequent need for phlebotomy 2, 4
• Symptomatic or progressive splenomegaly 2, 4
• Severe disease-related symptoms 2, 4
• Platelet count >1,500 × 10⁹/L (extreme thrombocytosis with bleeding risk) 2, 4
• Progressive leukocytosis 2, 4

Common Pitfalls to Avoid

• Do not accept hematocrit targets of 45-50%—this definitively increases thrombotic risk 2
• Avoid chlorambucil and ³²P in younger patients—these carry significantly increased leukemia risk 2
• Do not use hydroxyurea as first-line in patients <40 years—choose interferon-α instead 2, 4
• Avoid inadequate fluid replacement during phlebotomy—can precipitate hypotension in elderly or cardiovascular disease patients 2, 3
• Do not withhold aspirin without clear contraindications—the thrombotic benefit is well-established 1, 2

Monitoring Requirements

• Monitor hematocrit levels regularly to maintain target <45% 2, 3
• Evaluate for new thrombosis or bleeding every 3-6 months 2
• Assess symptom burden regularly 2
• Consider bone marrow biopsy prior to initiating cytoreductive therapy to rule out disease progression to myelofibrosis 2