Management of Polycythemia Vera
All patients with polycythemia vera should be treated with phlebotomy to maintain hematocrit strictly below 45% and low-dose aspirin (100mg daily), with cytoreductive therapy added for high-risk patients (age >60 years and/or history of thrombosis). 1, 2
First-Line Treatment Approach
- Phlebotomy is the cornerstone of treatment for all PV patients, with the goal of maintaining hematocrit <45% in men (with corresponding values for females) 1, 2
- Low-dose aspirin (81-100mg daily) should be administered to all patients without contraindications as it significantly reduces cardiovascular events 1, 3
- All patients should be managed aggressively for cardiovascular risk factors and advised to stop smoking 2
Risk Stratification
- Patients are classified into two risk categories 1, 3:
- Low-risk: Age <60 years and no history of thrombosis
- High-risk: Age ≥60 years and/or previous thrombotic events
Indications for Cytoreductive Therapy
Cytoreductive therapy should be initiated in patients with 2, 1:
- High-risk status (age >60 years and/or history of thrombosis)
- Poor tolerance of phlebotomy or frequent phlebotomy requirement
- Symptomatic or progressive splenomegaly
- Severe disease-related symptoms
- Platelet counts >1,500 × 10^9/L
- Progressive leukocytosis
Selection of Cytoreductive Agents
First-line cytoreductive options 2, 1:
- Hydroxyurea (starting at 500mg twice daily) is recommended for older patients (>40 years)
- Interferon-α is preferred for younger patients (<40 years) and women of childbearing age
- Ruxolitinib (JAK1/2 inhibitor) for patients with resistance or intolerance to hydroxyurea, providing hematocrit control, reducing spleen size, and improving PV-related symptoms
- Busulfan may be considered in elderly patients (>70 years) 2
Monitoring Response to Treatment
- Response to cytoreductive therapy should be evaluated using the European LeukemiaNet criteria for clinicohematologic response 2, 1
- Complete response is defined as 2:
- Hematocrit <45% without phlebotomy
- Platelet count <400 × 10^9/L
- White blood cell count <10 × 10^9/L
- No disease-related symptoms
Definition of Hydroxyurea Resistance/Intolerance
Resistance or intolerance to hydroxyurea is defined by any of the following 2, 1:
- Need for phlebotomy to maintain hematocrit <45% after 3 months of at least 2g/day of hydroxyurea
- Uncontrolled myeloproliferation (platelet count >400 × 10^9/L AND WBC count >10 × 10^9/L)
- Failure to reduce massive splenomegaly by >50% or relieve splenomegaly-related symptoms
- Cytopenia (neutrophils <1.0 × 10^9/L, platelets <100 × 10^9/L, or hemoglobin <10 g/dL)
- Presence of leg ulcers or other unacceptable side effects
Special Considerations
- Recent data shows that 55% of treated PV patients receive burdensome treatments (frequent phlebotomies and/or high-dose hydroxyurea), highlighting the need for therapy optimization 6
- JAK2 gene variant is present in >95% of PV patients, which helps distinguish it from secondary causes of erythrocytosis 5
- PV is associated with increased risk of both arterial thrombosis (16%) and venous thrombotic events (7%), which can involve unusual sites like splanchnic veins 5
- Disease progression can lead to myelofibrosis (12.7%) or acute myeloid leukemia (6.8%) 5
Common Pitfalls and Caveats
- Failure to maintain strict hematocrit control below 45% significantly increases thrombotic risk 1, 2
- Extreme thrombocytosis (≥1000 × 10^9/L) can lead to acquired von Willebrand disease and increased bleeding risk 5
- Long-term use of hydroxyurea or busulfan may increase the risk of leukemic transformation, particularly in younger patients 7, 8
- Monitoring for resistance or intolerance to hydroxyurea is essential, as approximately 25% of patients develop these issues 4