What is the initial management approach for a patient with Polycythemia Vera?

Initial Management of Polycythemia Vera

The initial management of polycythemia vera should include phlebotomy to maintain hematocrit <45% in men and <42% in women, along with low-dose aspirin (81-100 mg daily) for all patients without contraindications. 1

Diagnostic Workup

Before initiating treatment, a proper diagnostic evaluation should include:

• Complete blood count with differential
• Iron studies (serum iron, TIBC, ferritin, transferrin saturation)
• Serum erythropoietin level
• JAK2 V617F mutation testing (present in >95% of PV cases)
• Abdominal ultrasound to evaluate for splenomegaly 1, 2

Risk Stratification

Risk stratification is essential for determining appropriate management:

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

Management Algorithm

Step 1: All Patients

• Phlebotomy: Target hematocrit <45% in men, <42% in women
  • Induction phase: 300-450 ml of blood withdrawn weekly or twice weekly until target hematocrit is reached
  • Maintenance phase: Same blood volume but adjusted intervals based on hematocrit levels 4, 1
• Low-dose aspirin: 81-100 mg daily (unless contraindicated) 1, 3
• Aggressive management of cardiovascular risk factors: Hypertension, hyperlipidemia, diabetes, smoking 4, 1

Step 2: Additional Therapy Based on Risk

Low-risk patients:

• Continue phlebotomy and aspirin
• Monitor every 3-6 months with CBC and symptom assessment 1

High-risk patients:

• Add cytoreductive therapy (in addition to phlebotomy and aspirin) 4, 1, 3

Step 3: Indications for Cytoreductive Therapy

Cytoreductive therapy is indicated for:

• High-risk patients (age ≥60 years or history of thrombosis)
• Poor tolerance to phlebotomy
• Requirement for >5 phlebotomies per year
• Symptomatic or progressive splenomegaly
• Severe disease-related symptoms
• Platelet count >1500 × 10^9/l
• Leukocyte count >15 × 10^9/l 4, 1

Cytoreductive Therapy Options

1. First-line options:

   • Hydroxyurea: Generally preferred in older patients
   • Interferon-α: Preferred in younger patients and pregnant women 4, 1

2. Second-line options:

   • Ruxolitinib: For patients intolerant or resistant to hydroxyurea, particularly for symptom management (pruritus, splenomegaly) 4, 1
   • Busulfan: May be considered in very elderly patients (>70 years), used intermittently due to leukemogenicity concerns 1

Monitoring and Complications

• Regular monitoring every 3-6 months with CBC and symptom assessment
• Watch for complications of repeated phlebotomies:
  • Iron deficiency
  • Decreased oxygen-carrying capacity
  • Paradoxically increased blood viscosity due to iron-deficient red cells 1

Important Considerations

• The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces cardiovascular death and major thrombotic events compared to a target of 45-50% (HR 3.91; 95% CI 1.45-10.53) 4
• Thrombosis incidence under phlebotomy alone is approximately 0.8% per year 5
• In patients with extreme thrombocytosis (≥1000 × 10^9/L), monitor for acquired von Willebrand disease and increased bleeding risk 2
• Documented severe tissue iron deficiency with symptoms (pica, mouth paresthesia, esophagitis, restless legs) may require iron supplementation, but be cautious of hematocrit worsening 4

By following this structured approach to PV management, the risk of thrombotic complications can be significantly reduced while maintaining quality of life for patients.