What is the treatment for polycythemia?

Treatment of Polycythemia

The mainstay of treatment for polycythemia vera (PV) is phlebotomy to maintain hematocrit below 45% in men (with appropriate corresponding values for women and other races), combined with low-dose aspirin (81 mg/day) for all patients without contraindications. 1, 2

Types of Polycythemia and Diagnosis

• Polycythemia refers to either a real (true polycythemia) or spurious (apparent polycythemia) increase in red blood cell mass 1
• True polycythemia includes:
  • Polycythemia vera (PV) - a clonal myeloproliferative disorder
  • Secondary polycythemia (SP) - nonclonal increase often mediated by erythropoietin 1
• Apparent polycythemia results from plasma volume reduction (relative polycythemia) 1
• Diagnosis of PV typically requires JAK2 mutation testing (positive in >95% of cases) and complete blood count with peripheral smear 3, 2

Treatment Approach Based on Risk Stratification

Risk Categories in PV:

• Low risk: Age <60 years and no history of thrombosis 1
• High risk: Age ≥60 years or positive history of thrombosis 1

Treatment Algorithm:

1. All PV patients:

   • Phlebotomy to maintain hematocrit <45% 1, 2
   • Low-dose aspirin (81 mg/day) in absence of contraindications 1, 2

2. High-risk PV patients (add cytoreductive therapy):

   • First-line: Hydroxyurea 1, 4
   • Second-line options for hydroxyurea intolerance or resistance:
     • Ruxolitinib (particularly for symptoms like pruritus) 1, 4
     • Interferon-α (preferred in younger patients) 1, 4
     • Busulfan (preferred in very elderly patients) 1, 4

3. Special populations:

   • Women of childbearing age: Consider interferon-α as cytoreductive agent 1
   • Patients with intractable pruritus: Consider interferon-α or ruxolitinib 1

Treatment of Secondary Polycythemia

• Management depends on underlying cause and balances physiological benefit of increased hematocrit against risks of hyperviscosity 1
• For cyanotic congenital heart disease or high oxygen-affinity hemoglobinopathy: Judicious phlebotomy to hematocrit of 60% 1
• For chronic obstructive pulmonary disease (COPD): Graded phlebotomy to hematocrit of 55-60% 1
• For post-renal transplant erythrocytosis: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers 1
• For smoker's polycythemia: Smoking cessation 1

Management of Complications

Pruritus:

• First-line: Antihistamines (variable response) 1
• Second-line: Selective serotonin reuptake inhibitors like paroxetine (>80% response rate) 1
• Refractory cases: Interferon-α (up to 81% response rate) 1

Erythromelalgia and microvascular disturbances:

• Low-dose aspirin (81 mg/day) provides prompt relief in most cases 1
• For non-responders: Consider cytoreductive therapy to normalize platelet count 1

Monitoring and Follow-up

• Regular monitoring of hematocrit, platelet count, and white blood cell count 3
• Assess for hyperviscosity symptoms (headache, visual disturbances, dizziness) 3
• Monitor for disease progression to myelofibrosis (10-16% at 20 years) or acute leukemia (4-6.8% at 10-20 years) 4, 5

Important Caveats

• Aggressive phlebotomy should be avoided in cyanotic congenital heart disease due to stroke risk 1
• Iron replacement therapy should not be used indiscriminately for PV-associated pruritus 1
• Current treatment strategies have not been shown to prolong survival or reduce risk of leukemic/fibrotic progression 4
• The risk of thrombosis is higher in JAK2-mutated cases of essential thrombocythemia 5
• Controlled studies are needed to clarify the value of twice-daily vs. once-daily aspirin dosing 4, 5