Indications for Starting Hydroxyurea in Polycythemia Vera
Hydroxyurea should be initiated in all high-risk polycythemia vera patients, defined as those aged >60 years OR with any prior history of thrombosis, regardless of other factors. 1, 2
Risk Stratification Framework
High-risk patients requiring hydroxyurea include:
- Age >60 years (even without prior thrombosis) 1
- Any history of thrombosis at any age (arterial or venous, including unusual sites like splanchnic veins) 1, 3
Additional clinical scenarios warranting hydroxyurea initiation:
- Progressive leukocytosis despite phlebotomy and aspirin 1, 4
- Symptomatic or progressive splenomegaly unresponsive to conservative management 1
- Symptomatic thrombocytosis with platelet counts requiring cytoreduction 1
- Persistent disease-related symptoms (pruritus, night sweats, fatigue) despite phlebotomy 1
- Vasomotor/microvascular disturbances (headaches, chest pain, erythromelalgia) not responsive to aspirin 1
- Requirement for frequent phlebotomies to maintain hematocrit <45% 2
Treatment Goals and Monitoring
Target hematocrit <45% - this strict threshold reduces thrombotic events significantly compared to 45-50% (HR 3.91 for cardiovascular death/major thrombosis with higher targets) 1, 4
Target platelet count <400 × 10⁹/L to reduce thrombotic complications 2
Target WBC count <10 × 10⁹/L 2
Monitor complete blood counts every 4-8 weeks once stabilized 2
Important Clinical Considerations
Bone marrow biopsy should be performed before initiating cytoreductive therapy to rule out disease progression to myelofibrosis 1
All patients should receive phlebotomy plus low-dose aspirin (81-100 mg daily) as baseline therapy, with hydroxyurea added for high-risk features 1, 4, 3
The evidence strongly supports hydroxyurea as first-line cytoreductive therapy at any age for high-risk patients 1. While older studies raised concerns about leukemic transformation with hydroxyurea, more recent analyses identified other alkylating agents (not hydroxyurea alone) as the culprit 1. Meta-analysis data shows leukemic transformation occurs at 0.4% persons/year with hydroxyurea treatment 5.
Alternative Agents
Interferon-alpha should be considered instead of hydroxyurea for:
- Younger patients (<40 years) concerned about long-term leukemogenic risk 2
- Pregnant patients requiring cytoreduction 1, 2
- Patients preferring to avoid hydroxyurea 1
Ruxolitinib is reserved for patients resistant or intolerant to hydroxyurea, demonstrating 68.2% hematocrit control and 85.1% phlebotomy-free rates at 24 months 6, 3
Common Pitfalls to Avoid
Do not delay cytoreductive therapy in high-risk patients while attempting phlebotomy alone - the combination is superior 1, 3
Do not use age 65 as a cutoff; the threshold is >60 years 1
Do not overlook JAK2 mutation status in risk assessment, though age and thrombosis history remain the primary drivers for treatment decisions 1
Resistance to hydroxyurea is defined as platelet count >600 × 10⁹/L after 3 months of adequate dosing OR need for continued phlebotomy despite 3 months of treatment 2