What is the initial approach to managing a case of polycythaemia?

Management of Polycythemia Vera

The initial approach to managing 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, as part of a comprehensive approach to reduce thrombotic risk. 1

Diagnostic Evaluation

• Initial workup for elevated hemoglobin/hematocrit should include:
  • Complete blood count with differential
  • Iron studies
  • Serum erythropoietin level
  • JAK2 V617F mutation testing (present in >95% of PV cases) 1, 2
• Bone marrow biopsy is essential for diagnosis and baseline assessment 3
• Confirm persistent elevation with repeat measurements 1

Risk Stratification

Risk stratification guides treatment intensity:

• Low-risk patients:

  • Age <60 years AND
  • No history of thrombosis 4, 1

• High-risk patients:

  • Age ≥60 years OR
  • Prior history of thrombosis 4, 1

Treatment Algorithm

For ALL Patients with Polycythemia Vera:

1. Therapeutic phlebotomy:

   • Target hematocrit <45% in men and <42% in women 1
   • Initial phase: 300-450 mL blood withdrawn weekly or twice weekly
   • Maintenance phase: Adjust intervals based on hematocrit levels 1
   • Monitor for symptoms of hyperviscosity during procedure 1

2. Low-dose aspirin (81-100 mg daily) for all patients without contraindications 1

3. Aggressive management of cardiovascular risk factors:

   • Hypertension, hyperlipidemia, diabetes, smoking cessation 1

Additional Treatment for High-Risk Patients:

Cytoreductive therapy is indicated for:

• High-risk patients (age ≥60 years or prior thrombosis)
• Poor tolerance to phlebotomy
• Requirement for frequent phlebotomies
• Symptomatic or progressive splenomegaly
• Severe disease-related symptoms
• Elevated platelet or leukocyte counts 4, 1

First-line cytoreductive options:

• Hydroxyurea:

  • Initial dosage: 500 mg twice daily orally 4
  • Preferred in older patients 1
  • Monitor for adverse effects: neutropenia, mucocutaneous changes, leg ulcers 4

• Interferon-α:

  • Initial dosage: 3 million units subcutaneously 3 times weekly 4
  • Preferred in younger patients and pregnant women 1
  • Monitor for adverse effects: flu-like symptoms, fatigue, depression 4

Second-line options:

• Ruxolitinib:

  • For patients intolerant or resistant to hydroxyurea
  • Particularly effective for symptom management and splenomegaly 4, 1

• Busulfan:

  • Initial dosage: 4 mg/day 4
  • Consider in very elderly patients 1
  • Monitor for potential toxicity: pulmonary fibrosis, bone marrow aplasia 4

Monitoring

• Regular follow-up every 3-6 months with:

  • Complete blood count
  • Assessment of symptoms
  • Evaluation for disease progression 4, 1

• Monitor for complications:

  • Iron deficiency from repeated phlebotomies
  • Thrombotic events
  • Bleeding complications
  • Disease transformation to myelofibrosis (occurs in ~12.7% of patients) or acute myeloid leukemia (occurs in ~6.8% of patients) 1, 2

Common Pitfalls and Caveats

• Inadequate hematocrit control: The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces cardiovascular death and major thrombotic events 1

• Overuse of phlebotomy: Can lead to iron deficiency, decreased oxygen-carrying capacity, and paradoxically increased blood viscosity 1

• Ignoring symptoms: Disease-related symptoms like pruritus, erythromelalgia, and visual disturbances should prompt consideration of cytoreductive therapy even in low-risk patients 2

• Neglecting cardiovascular risk factors: Aggressive management of these factors is essential in PV management 1

• Overlooking extreme thrombocytosis: Platelet counts ≥1000 × 10^9/L can lead to acquired von Willebrand disease and increased bleeding risk 2

By following this structured approach to polycythemia vera management, clinicians can effectively reduce thrombotic risk while managing symptoms and monitoring for disease progression.