Initial Treatment for Polycythemia Vera
Phlebotomy to maintain hematocrit strictly below 45% combined with low-dose aspirin (81-100 mg daily) is the cornerstone initial treatment for all patients with polycythemia vera. 1, 2
Immediate First-Line Therapy for All Patients
Phlebotomy
- Target hematocrit <45% in men through therapeutic phlebotomy, which is the absolute cornerstone of initial management 2, 3
- Women typically require lower targets around 42% due to physiological differences 2, 4
- The CYTO-PV study definitively demonstrated that maintaining hematocrit <45% significantly reduces thrombotic events compared to targets of 45-50% 2
- Perform phlebotomy with careful fluid replacement to prevent hypotension, particularly in elderly patients with cardiovascular disease 2
- This aggressive phlebotomy approach has improved median survival to >10 years compared to <4 years historically 2
Low-Dose Aspirin
- Administer 81-100 mg daily to all patients without contraindications 2, 3
- The ECLAP study demonstrated significant reduction in cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism 2
- Low-dose aspirin (40-100 mg) does not increase bleeding risk and is particularly effective for microvascular symptoms including erythromelalgia and headaches 1, 2
- Excessive aspirin use is contraindicated, but lower doses are both safe and effective 1
Cardiovascular Risk Factor Management
- Aggressively manage hypertension, hyperlipidemia, and diabetes 2
- Mandatory smoking cessation counseling and support 2
Risk Stratification to Guide Additional Therapy
After initiating phlebotomy and aspirin, stratify patients into risk categories:
Low-Risk Patients (Age <60 years AND no thrombosis history)
- Phlebotomy and low-dose aspirin are generally sufficient as initial treatment 2
- Monitor every 3-6 months for thrombosis, bleeding, or disease progression 2
High-Risk Patients (Age ≥60 years OR history of thrombosis)
- Add cytoreductive therapy to phlebotomy and aspirin 2, 3
- Hydroxyurea is the first-line cytoreductive agent (Level II, A evidence) with starting dose 500 mg twice daily 2, 4
- Interferon-α is an alternative first-line option (Level III, B evidence), particularly preferred for:
Additional Indications for Cytoreductive Therapy
Even in low-risk patients, consider adding cytoreductive therapy for:
- Intolerance or frequent need for phlebotomy 2
- Symptomatic or progressive splenomegaly 2
- Severe disease-related symptoms 2
- Platelet count >1,500 × 10⁹/L (extreme thrombocytosis with bleeding risk) 2
- Progressive leukocytosis 2
Important Caveats and Pitfalls
What to Avoid
- Never accept hematocrit targets of 45-50% as the CYTO-PV trial definitively showed increased thrombotic risk at these levels 2
- Avoid chlorambucil and ³²P in younger patients due to significantly increased leukemia risk 2
- Use hydroxyurea with caution in patients <40 years due to potential leukemogenic risk with prolonged exposure 2, 4
- Avoid inadequate fluid replacement during phlebotomy, which can precipitate hypotension 2
Monitoring Requirements
- Assess for new thrombosis or bleeding at every visit 2
- Evaluate for signs/symptoms of disease progression every 3-6 months 2
- Consider bone marrow aspirate and biopsy to rule out progression to myelofibrosis prior to initiating cytoreductive therapy 2
- Monitor hematocrit levels regularly to maintain target values 2
Special Populations
- Pregnant patients: Use interferon-α exclusively as the cytoreductive agent of choice over hydroxyurea 2, 4
- Elderly patients (>70 years): Busulfan may be considered only in this age group 2
Symptom-Specific Management
Pruritus (occurs in 33-48% of patients)
- Selective serotonin reuptake inhibitors (e.g., paroxetine) achieve >80% response rate 1, 2
- Interferon-α reduces pruritus in up to 81% of affected patients 1, 2
- Antihistamines are an alternative option though responses are unpredictable 1, 2