What is the treatment for polycythemia?

Treatment for Polycythemia Vera

The cornerstone treatment for polycythemia vera includes therapeutic phlebotomy to maintain hematocrit <45% and low-dose aspirin (81-100 mg daily) for all patients, with cytoreductive therapy added for high-risk patients (age >60 years or history of thrombosis). 1

Diagnosis Confirmation

Before initiating treatment, confirm the diagnosis:

• Check for JAK2 V617F mutation (present in >95% of PV cases)
• Evaluate hemoglobin/hematocrit levels (>16.5 g/dL/49% in men or >16.0 g/dL/48% in women)
• Measure serum erythropoietin (typically low in PV)
• Rule out secondary causes of polycythemia

Risk Stratification

Patients are classified into two risk categories:

• Low-risk: Age ≤60 years AND no history of thrombosis
• High-risk: Age >60 years OR history of thrombosis

First-Line Treatment for All Patients

1. Therapeutic phlebotomy:

   • Target hematocrit <45% (shown to significantly reduce thrombotic events) 2
   • Initially may require frequent phlebotomies, then maintenance as needed
   • Avoid aggressive phlebotomy in patients with cyanotic heart disease due to stroke risk 1
   • Consider replacing with equal volume of dextrose or saline to avoid dehydration 1

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

   • Reduces risk of cardiovascular events 2
   • Contraindicated if extreme thrombocytosis (>1,500 × 10⁹/L) due to bleeding risk 1

Additional Treatment for High-Risk Patients

Cytoreductive therapy for patients who are:

• Age >60 years OR
• Have history of thrombosis OR
• Have symptomatic splenomegaly OR
• Have significant thrombocytosis or leukocytosis

Options include:

1. Hydroxyurea (first-line):

   • Initial dose: 15-20 mg/kg/day 1
   • Adjust to maintain leukocytes >2,500/μL and platelets >100,000/μL
   • Monitor for cytopenia and mucocutaneous lesions

2. Interferon-alfa (alternative first-line):

   • Preferred for younger patients and women of childbearing age 1
   • No known leukemogenic potential
   • Can reduce JAK2V617F allele burden
   • Monitor for flu-like symptoms, depression, and thyroid dysfunction

3. Ruxolitinib (second-line):

   • For patients intolerant or resistant to hydroxyurea 3
   • Particularly effective for pruritus and splenomegaly
   • Monitor for cytopenia and increased infection risk

Special Clinical Scenarios

1. Post-renal transplant erythrocytosis:

   • ACE inhibitors or angiotensin II receptor blockers are effective 2, 1

2. COPD-associated erythrocytosis:

   • ACE inhibitors or theophylline may be beneficial 2, 1
   • Judicious phlebotomy to hematocrit of 55-60% for symptomatic hyperviscosity 1

3. Intractable pruritus:

   • Interferon-alfa or JAK inhibitors (ruxolitinib) 2, 3
   • Antihistamines as adjunctive therapy 2

4. Pregnancy:

   • Interferon-alfa is the preferred cytoreductive agent 1
   • Avoid hydroxyurea due to teratogenic potential

Monitoring

• CBC every 2-3 months initially, then every 3-6 months if stable 1
• Regular evaluation of spleen size
• Monitor for symptoms of hyperviscosity
• Assess for disease progression to myelofibrosis or acute leukemia
• Aggressive control of cardiovascular risk factors, including smoking cessation 1

Pitfalls to Avoid

1. Iron deficiency from excessive phlebotomy:

   • Can lead to microcytic anemia with reduced oxygen-carrying capacity
   • Increases stroke risk 1
   • Don't supplement iron routinely, but consider if symptomatic

2. Overtreatment with cytoreductive agents:

   • Can lead to cytopenias and increased infection risk
   • Balance thrombosis risk reduction against side effects

3. Undertreatment:

   • Failure to maintain hematocrit <45% increases thrombosis risk
   • Inadequate cytoreduction in high-risk patients

4. Missing secondary polycythemia:

   • Always rule out hypoxic causes (COPD, sleep apnea)
   • Check for renal tumors, hepatocellular carcinoma
   • Inquire about androgen or erythropoietin use

By following this treatment algorithm and avoiding common pitfalls, the risk of thrombotic complications, which are the main cause of morbidity and mortality in polycythemia vera, can be significantly reduced.