What is the management of polycythemia vera?

Management of Polycythemia Vera

The management of polycythemia vera should focus on reducing thrombotic risk through phlebotomy to maintain hematocrit <45%, low-dose aspirin (81-100 mg/day) for all patients without contraindications, and cytoreductive therapy for high-risk patients (age >60 years and/or history of thrombosis). 1

Risk Stratification

Risk stratification is essential for determining appropriate treatment:

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

First-Line Treatment for All Patients

Phlebotomy

• Target hematocrit <45% based on the CYTO-PV study 1
• May require lower targets (e.g., 42%) for female patients 1
• Can be used as emergency therapy at diagnosis for very high hematocrit and signs of hyperviscosity 1
• Blood transfusions are generally contraindicated as they would further increase red cell mass 2, 3

Low-dose Aspirin

• Recommended for all patients without contraindications 1
• Significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism 1
• Effective for alleviating microvascular symptoms including erythromelalgia and headaches 1

Cardiovascular Risk Factor Management

• Aggressive management of vascular risk factors (e.g., smoking cessation) 1

Treatment Based on Risk Category

Low-Risk Patients

• Phlebotomy and low-dose aspirin are generally sufficient 1
• Cytoreductive therapy is not recommended as initial treatment 1
• Consider cytoreductive therapy if:
  • New thrombosis or disease-related major bleeding occurs 1
  • Poor tolerance of frequent phlebotomy 1
  • Symptomatic or progressive splenomegaly 1
  • Symptomatic thrombocytosis 1
  • Progressive leukocytosis 1
  • Progressive disease-related symptoms (pruritus, night sweats, fatigue) 1

High-Risk Patients

• Phlebotomy and low-dose aspirin plus cytoreductive therapy 1
• First-line cytoreductive options:
  • Hydroxyurea (recommended with level II, A evidence) 1
  • Interferon-α (recommended with level III, B evidence) - consider for younger patients or pregnant patients 1

Monitoring and Follow-up

• Monitor for new thrombosis or bleeding 1
• Evaluate for signs/symptoms of disease progression every 3-6 months or more frequently if clinically indicated 1
• Assess symptom burden regularly 1
• Perform bone marrow aspirate and biopsy to rule out disease progression to myelofibrosis prior to initiating cytoreductive therapy 1

Management of Specific Symptoms

Pruritus

• Selective serotonin receptor antagonists are effective 1
• Interferon-α or JAK2 inhibitors can be used 1
• Other options include antihistamines 1

Second-Line Therapy

Indications for Change of Cytoreductive Therapy

• Inadequate response to first-line therapy 1
• Frequent/persistent need for phlebotomy with poor tolerance 1
• Symptomatic or progressive splenomegaly 1
• Symptomatic thrombocytosis 1
• Progressive leukocytosis 1
• Progressive disease-related symptoms 1

Second-Line Options

• Ruxolitinib (JAK inhibitor) for patients resistant to or intolerant of hydroxyurea 2, 4
• Switch between hydroxyurea and interferon if not previously used 1
• Consider clinical trial participation 1

Special Considerations

Extreme Thrombocytosis (>1500 × 10^9/L)

• Considered an indication for cytoreductive therapy 1
• May be associated with acquired von Willebrand disease and increased bleeding risk 4

Perioperative Management

• Continue low-dose aspirin therapy during the perioperative period 2, 3
• Ensure hematocrit is well-controlled before elective procedures 5

Pregnancy

• Interferon-α is preferred over hydroxyurea for cytoreductive therapy 1

Long-Term Complications to Monitor

• Transformation to myelofibrosis (occurs in approximately 12.7% of patients) 4
• Development of acute myeloid leukemia (occurs in approximately 6.8% of patients) 4
• Thrombotic and hemorrhagic events 5, 6