How is elevated hemoglobin (polycythemia) treated?

Treatment of Elevated Hemoglobin (Polycythemia)

Therapeutic phlebotomy is the cornerstone treatment for polycythemia vera (PV), with the goal of maintaining hematocrit below 45% to reduce thrombotic risk and improve survival. 1

Diagnosis and Classification

Before initiating treatment, it's crucial to determine the type of polycythemia:

1. True Polycythemia:

   • Polycythemia Vera (PV): A clonal myeloproliferative disorder associated with JAK2 mutations
   • Secondary Polycythemia: Non-clonal increase in red cell mass, often erythropoietin (EPO) mediated

2. Apparent Polycythemia:

   • Reduced plasma volume (relative polycythemia)
   • Normal red cell mass with elevated hemoglobin/hematocrit

Diagnostic workup should include:

• Complete blood count
• Serum EPO level (low in PV, normal/high in secondary polycythemia)
• JAK2 mutation testing
• Bone marrow examination in selected cases

Risk Stratification for PV

Patients with PV should be stratified into risk categories 1:

Risk Category	Criteria
Low Risk	Age <60 years AND no history of thrombosis
High Risk	Age ≥60 years OR history of thrombosis

Treatment Algorithm

1. Polycythemia Vera

Low-Risk Patients:

• Therapeutic phlebotomy to maintain hematocrit <45% (possibly <42% in women)
• Low-dose aspirin (81-100 mg daily) unless contraindicated
• Regular monitoring of complete blood count

High-Risk Patients:

• Therapeutic phlebotomy to maintain hematocrit <45%
• Cytoreductive therapy (first-line options):
  • Hydroxyurea
  • Interferon-α (particularly in younger patients)
• Low-dose aspirin (81-100 mg daily)
• Consider ruxolitinib for patients resistant/intolerant to hydroxyurea

2. Secondary Polycythemia

• Treat underlying cause when possible:
  • Hypoxia-driven: Oxygen therapy, CPAP for sleep apnea
  • Tumor-related: Surgical removal if possible
  • Smoking cessation for smoker's polycythemia
• Therapeutic phlebotomy may be needed if symptomatic or hematocrit is significantly elevated

3. Relative Polycythemia

• Address underlying causes (dehydration, diuretics)
• Rarely requires specific treatment

Phlebotomy Protocol

• Initial frequency: Weekly removal of 450-500 mL until target hematocrit is achieved
• Maintenance: Individualized schedule based on response (typically every 2-3 months)
• Monitor for symptoms of iron deficiency

Monitoring

• Regular complete blood count
• Assessment for thrombotic or bleeding complications
• Monitoring for disease progression to myelofibrosis or acute leukemia

Special Considerations

• Iron supplementation: Only for severe symptomatic iron deficiency
• Avoid chlorambucil and phosphorus-32 due to increased risk of leukemic transformation 1
• Pregnancy: Requires specialized management; interferon-α is preferred over hydroxyurea
• Masked PV: Some patients may have normal hemoglobin/hematocrit but still have PV due to concurrent blood loss or expanded plasma volume 2

Common Pitfalls

1. Failure to maintain hematocrit <45%, which significantly increases thrombotic risk
2. Underuse of aspirin in eligible patients
3. Overtreatment of low-risk patients with cytoreductive therapy
4. Inadequate monitoring for disease progression
5. Missing masked PV in patients with normal hemoglobin but other features of myeloproliferative neoplasm

Untreated PV may lead to survival of only 6-18 months, whereas adequate treatment can extend life expectancy to more than 10 years 3. Regular follow-up and adherence to treatment are essential for optimal outcomes.