Management of Polycythemia Vera
All patients with polycythemia vera should be managed with phlebotomy to maintain hematocrit below 45% and low-dose aspirin (81-100mg daily), with cytoreductive therapy added for high-risk patients (age >60 years and/or history of thrombosis). 1, 2, 3
First-Line Treatment Approach
Universal Management Strategies
- Phlebotomy to maintain hematocrit strictly below 45% in men (consider lower targets of approximately 42% for women and African Americans) 1, 2, 3
- Low-dose aspirin (81-100mg daily) for all patients without contraindications 1, 2
- Aggressive management of cardiovascular risk factors and smoking cessation 1
- Careful monitoring of hematocrit levels to maintain target values 3
Risk Stratification
- High-risk patients: Age >60 years and/or history of thrombosis 2, 4
- Low-risk patients: Absence of both risk factors 2, 4
Cytoreductive Therapy
Indications for Cytoreductive Therapy
- High-risk status (age >60 years and/or history of thrombosis) 1, 2
- Poor tolerance of phlebotomy or frequent phlebotomy requirement (>5 phlebotomies per year) 1, 5
- Symptomatic or progressive splenomegaly 1
- Severe disease-related symptoms 1
- Platelet counts >1,500 × 10^9/L 1
- Progressive leukocytosis 1
First-Line Cytoreductive Options
- Hydroxyurea: Preferred for patients >40 years old (starting dose 500mg twice daily) 1, 2
- Interferon-α: Preferred for younger patients (<40 years) and women of childbearing age 1, 2
- Pegylated interferon has shown clinical efficacy with normalization of myeloproliferation and decreased JAK2V617F allele burden 1
Second-Line Therapy
- Consider interferon-α if hydroxyurea resistance or intolerance develops 1
- Busulfan may be considered in elderly patients (>70 years) 1
- Ruxolitinib for patients with symptoms reminiscent of post-PV myelofibrosis or protracted pruritus 6, 7
Monitoring Treatment Response
Response Criteria
- Complete response: Hematocrit <45% without phlebotomy, platelet count <400 × 10^9/L, WBC count <10 × 10^9/L, and no disease-related symptoms 1
- Partial response: Hematocrit <45% without phlebotomy or response in three or more of the other criteria 1
Resistance/Intolerance to Hydroxyurea
- Need for phlebotomy to keep hematocrit <45% after 3 months of at least 2g/day of hydroxyurea 1
- Uncontrolled myeloproliferation (platelet count >400 × 10^9/L AND WBC count >10 × 10^9/L) after 3 months 1
- Failure to reduce massive splenomegaly or relieve splenomegaly-related symptoms 1
- Cytopenias or unacceptable side effects at any dose 1
Long-Term Outcomes and Complications
- Median survival exceeds 35 years in young patients with PV 6
- 20-year rates of thrombotic, fibrotic, or leukemic events are 26%, 16%, and 4%, respectively 6
- Progression to myelofibrosis occurs in approximately 7% at 10 years and 20% at 20 years 5
- Leukemic transformation rate is approximately 3% at 10 years 8
Special Considerations
Phlebotomy Technique
- Perform under careful conditions with appropriate fluid replacement to avoid hypotension or fluid overload, especially in patients with cardiovascular disease 1, 3
- Blood transfusions are generally contraindicated as they would further increase red cell mass and exacerbate hyperviscosity 9
Pregnancy
- Interferon-α is the preferred cytoreductive agent during pregnancy as hydroxyurea is contraindicated 7
- Continue low-dose aspirin throughout pregnancy unless contraindicated 7
Common Pitfalls and Caveats
- Failure to maintain strict hematocrit control (<45%) significantly increases thrombotic risk 3
- Cytoreductive therapy should not be used in low-risk patients with well-controlled cardiovascular risk factors 1
- Current treatment strategies have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression 6
- Extreme thrombocytosis (≥1000 × 10^9/L) may be associated with acquired von Willebrand disease and increased bleeding risk 4
- Monitoring of molecular response (JAK2V617F allele burden) is not routinely recommended except when using interferon-α 1