What is the initial treatment for polycythemia?

Initial Treatment for Polycythemia

The initial treatment for polycythemia vera should include therapeutic phlebotomy to maintain a hematocrit <45% in men and <42% in women, along with low-dose aspirin (81-100 mg daily) in the absence of contraindications. 1, 2

Diagnostic Approach Before Treatment

Before initiating treatment, confirm the diagnosis with:

• Complete blood count with differential
• JAK2 V617F mutation testing (present in >95% of PV cases)
• Serum erythropoietin level (low in PV, elevated in secondary polycythemia)
• Iron studies to rule out iron deficiency
• Evaluation for secondary causes of polycythemia 1

Treatment Algorithm Based on Risk Stratification

Step 1: Risk Assessment

Categorize patients into risk groups:

• High Risk: Age ≥60 years OR history of thrombosis
• Low Risk: Age <60 years AND no history of thrombosis 1, 3

Step 2: Initial Treatment for All Patients with PV

1. Therapeutic phlebotomy:

   • Target: Hematocrit <45% in men, <42% in women
   • Remove 450-500 mL of blood per session
   • Replace with equal volume of saline or dextrose
   • Monitor vital signs during procedure 1, 2

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

   • Contraindicated if platelet count >1,500 × 10^9/L due to bleeding risk
   • Significantly reduces cardiovascular death, myocardial infarction, stroke, and venous thromboembolism 1, 2

Step 3: Additional Treatment Based on Risk

• High-risk patients: Add cytoreductive therapy (hydroxyurea first-line) 1, 3
• Low-risk patients: Phlebotomy and aspirin alone may be sufficient 1, 3

Evidence Supporting This Approach

The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduced cardiovascular death and major thrombotic events compared to a target of 45-50% (hazard ratio 3.91,95% CI 1.45-10.53) 4. This landmark study provides strong evidence for strict hematocrit control.

Cytoreductive Therapy Indications

Consider adding cytoreductive therapy if:

• Patient requires >5 phlebotomies per year
• Patient has persistent symptoms despite phlebotomy
• High-risk patient (age ≥60 or prior thrombosis)
• Significant splenomegaly or cytosis 1, 3

Common Pitfalls and Caveats

1. Iron deficiency from repeated phlebotomies: Can paradoxically increase blood viscosity despite lower hematocrit
2. Overhydration before hematocrit measurement: May falsely lower hematocrit values
3. Inadequate thrombosis prophylaxis: Failure to prescribe aspirin when indicated
4. Missing secondary causes: Treating as primary polycythemia when secondary causes exist (smoking, sleep apnea, etc.)
5. Ignoring cardiovascular risk factors: These should be aggressively managed alongside PV treatment 1

Monitoring

• Check hematocrit and complete blood count after each phlebotomy initially
• Once stable, monitor every 3-6 months
• Assess for disease-related symptoms (pruritus, night sweats, fatigue)
• Watch for signs of disease progression that might warrant therapy adjustment 1