How is polycythemia managed?

Management of Polycythemia Vera

All patients with polycythemia vera should be managed with phlebotomy to maintain hematocrit below 45% and low-dose aspirin (81-100 mg daily), with cytoreductive therapy added for high-risk patients or those with specific indications. 1, 2

Risk Stratification

Risk stratification is essential to guide treatment decisions:

• 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 Patients:

1. Phlebotomy:

   • Target hematocrit <45% in men and <42% in women 1, 2
   • Schedule frequency based on individual response
   • Monitor for hypotension during procedure, especially in patients with cardiovascular disease 2

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

   • Significantly reduces cardiovascular death, non-fatal myocardial infarction, stroke, and venous thromboembolism 1
   • Contraindicated in patients with history of significant bleeding or extreme thrombocytosis (>1,500 × 10^9/L) due to increased bleeding risk 2

Additional Therapy for High-Risk Patients:

Cytoreductive therapy is indicated for:

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

Cytoreductive Therapy Options

First-Line Cytoreductive Agents:

1. Hydroxyurea (first-line in most patients):

   • Starting dose: 500 mg twice daily, adjusted based on response
   • Advantages: Effective at reducing thrombotic risk, well-tolerated in older patients
   • Caution in young patients (<40 years) due to potential leukemogenicity with long-term use 1, 2

2. Interferon-α (alternative first-line, especially in younger patients):

   • Dosage: 3 million units subcutaneously 3 times weekly
   • Advantages: Non-leukemogenic, can induce hematologic responses in up to 80% of patients
   • Particularly suitable for younger patients and pregnant women 1, 2

Second-Line Cytoreductive Agents:

1. Ruxolitinib:

   • For patients intolerant or resistant to hydroxyurea
   • Particularly effective for symptom management (pruritus, splenomegaly) 1, 3

2. Busulfan:

   • Consider in very elderly patients (>70 years)
   • Used intermittently due to concerns about leukemogenicity 1

Monitoring and Follow-up

• Complete blood count every 3-6 months
• Assess symptoms at each visit
• Consider bone marrow biopsy if signs of disease progression 2
• Aggressively manage cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, smoking) 1, 4

Definition of Treatment Failure/Resistance

Hydroxyurea resistance/intolerance is defined by any of the following after 3 months of treatment with at least 2 g/day:

• Need for phlebotomy to keep hematocrit <45%
• Uncontrolled myeloproliferation (platelet count >400 × 10^9/L AND WBC >10 × 10^9/L)
• Failure to reduce massive splenomegaly by >50%
• Cytopenias or unacceptable side effects (leg ulcers, mucocutaneous manifestations) 1

Common Pitfalls to Avoid

• Undertreatment: Failing to maintain strict hematocrit control (<45%)
• Overaggressive phlebotomy: Can cause hypotension or iron deficiency
• Ignoring cardiovascular risk factors: These significantly contribute to morbidity and mortality
• Inappropriate aspirin use: Avoid in patients with extreme thrombocytosis or bleeding history
• Delayed cytoreductive therapy: Should be promptly initiated in high-risk patients or those with indications 2, 4

The management of polycythemia vera requires vigilant monitoring and appropriate risk-adapted therapy to prevent thrombotic complications, which are the major cause of morbidity and mortality in these patients 5.