What is the management of polycythemia vera (PV)?

Management of Polycythemia Vera (PV)

The management of polycythemia vera requires phlebotomy to maintain hematocrit <45% plus low-dose aspirin (81-100 mg/day) for all patients, with cytoreductive therapy added for high-risk patients (age ≥60 years or history of thrombosis). 1

Risk Stratification

Risk stratification is essential for determining appropriate treatment:

• Low-risk patients: Age <60 years AND no history of thrombosis
• High-risk patients: Age ≥60 years OR history of thrombosis 1, 2

First-Line Management for All PV Patients

1. Phlebotomy:

   • Target hematocrit <45% for all patients regardless of gender 1
   • Consider lower target (42%) for women 1
   • Monitor hematocrit every 3-6 months or more frequently if clinically indicated 1

2. Low-dose aspirin (81-100 mg daily):

   • Reduces thrombotic risk
   • Particularly effective for microvascular symptoms like erythromelalgia 1
   • Contraindicated in patients with history of major bleeding or platelet count >1,500 × 10^9/L 3

3. Aggressive management of cardiovascular risk factors:

   • Control hypertension, hyperlipidemia, diabetes
   • Smoking cessation 3, 1

Cytoreductive Therapy Indications

Cytoreductive therapy is indicated for:

• All high-risk patients (age ≥60 years or history of thrombosis) 1, 2
• Low-risk patients with:
  • Poor tolerance to phlebotomy or frequent phlebotomy requirement
  • Symptomatic or progressive splenomegaly
  • Severe disease-related symptoms
  • Platelet count >1,500 × 10^9/L
  • Progressive leukocytosis 3, 1

Cytoreductive Therapy Options

1. First-line options:

   • Hydroxyurea: Preferred for most high-risk patients, especially those >40 years 3, 1
   • Interferon-α: Preferred for younger patients (<40 years) and women of childbearing age 1

2. Second-line options:

   • Ruxolitinib: For patients intolerant or resistant to hydroxyurea 1, 4
   • Busulfan: May be considered in elderly patients (>70 years) 3, 1

Monitoring and Response Assessment

1. Hematologic response monitoring:

   • Regular assessment of complete blood counts
   • Monitor for resistance/intolerance to hydroxyurea using ELN criteria 3:
     • Need for phlebotomy despite 3 months of hydroxyurea ≥2 g/day
     • Uncontrolled myeloproliferation (platelets >400 × 10^9/L AND WBC >10 × 10^9/L)
     • Failure to reduce massive splenomegaly by >50%

2. Complications monitoring:

   • Signs of disease progression to myelofibrosis (occurs in ~12.7% of patients) 4
   • Development of acute myeloid leukemia (occurs in ~6.8% of patients) 4
   • Thrombotic or bleeding complications

Special Considerations

• Iron status monitoring: Repeated phlebotomies can lead to iron deficiency 1
• Pruritus management: Severe, persistent pruritus may require ruxolitinib 4
• Splenomegaly: Marked splenomegaly not responding to first-line therapy may benefit from ruxolitinib 4

Treatment Efficacy and Outcomes

• Proper management with phlebotomy and aspirin significantly improves survival compared to historical cohorts 3
• With current management approaches, median survival is approximately 14-27 years 4
• Low-risk PV patients treated with phlebotomies alone have a thrombosis incidence rate of 0.8% per year 5
• The 10-year probability of myelofibrosis is approximately 7%, increasing to 20% at 20 years 5

Common Pitfalls to Avoid

• Inadequate hematocrit control: Only 32-44% of patients maintain hematocrit <45% with phlebotomy alone 5
• Overlooking cardiovascular risk factors: These significantly contribute to thrombotic risk 3, 1
• Delaying cytoreductive therapy in high-risk patients or those with poor phlebotomy tolerance
• Excessive phlebotomy without monitoring iron status, which can compromise oxygen transport 1