How do you manage a patient with polycythaemia?

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 This approach forms the cornerstone of treatment to reduce thrombotic risk, which is the major cause of morbidity and mortality in these patients.

Diagnostic Evaluation

Before initiating treatment, a proper diagnostic workup is essential:

• Complete blood count with differential
• Iron studies
• Serum erythropoietin level
• JAK2 V617F mutation testing (present in >95% of cases) 1, 2
• Bone marrow biopsy may be required for definitive diagnosis
• Arterial blood gas analysis to exclude hypoxemia-related secondary polycythemia 1

Risk Stratification

Risk assessment guides treatment intensity:

• Low-risk patients: Age <60 years with no history of thrombosis
• High-risk patients: Age ≥60 years or prior history of thrombosis 1

Treatment Algorithm

Step 1: Initial Management (All Patients)

1. Therapeutic phlebotomy:

   • Target hematocrit <45% in men and <42% in women
   • Induction phase: 300-450 ml blood withdrawn weekly or twice weekly
   • Maintenance phase: Adjust intervals based on hematocrit levels 1
   • The CYTO-PV trial demonstrated that maintaining hematocrit <45% significantly reduces cardiovascular death and major thrombotic events (hazard ratio 3.91) 1, 3

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

   • For all patients without contraindications
   • Reduces thrombotic risk 1, 2

Step 2: 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 1

First-line cytoreductive options:

1. Hydroxyurea:

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

2. Interferon-α:

   • Preferred in younger patients and pregnant women
   • Initial dosage: 3 million units subcutaneously 3 times weekly
   • Monitor for adverse effects: flu-like symptoms, fatigue, depression 1, 5

Second-line options:

1. Ruxolitinib:

   • For patients intolerant or resistant to hydroxyurea
   • Particularly effective for symptom management and splenomegaly 1, 2

2. Busulfan:

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

Monitoring and Follow-up

• Regular follow-up every 3-6 months
• Complete blood count at each visit
• Assessment of symptoms and disease progression
• Evaluation for complications:
  • Iron deficiency from repeated phlebotomies
  • Thrombotic events (arterial and venous)
  • Bleeding complications (especially with extreme thrombocytosis)
  • Disease transformation to myelofibrosis (occurs in 12.7% of patients) or acute myeloid leukemia (occurs in 6.8% of patients) 1, 2

Special Considerations

• Women and African Americans: Target a lower hematocrit (42%) due to physiological differences 1
• Extreme thrombocytosis (≥1000 × 10^9/L): Monitor for acquired von Willebrand disease and increased bleeding risk 2
• Symptom management: Ruxolitinib is particularly effective for pruritus and splenomegaly 2
• Cardiovascular risk factors: Address modifiable risk factors such as smoking and cardiometabolic disease to further reduce thrombosis risk 4

Common Pitfalls to Avoid

1. Inadequate hematocrit control: Maintaining strict hematocrit control (<45%) is essential to reduce thrombotic events
2. Overlooking aspirin contraindications: Assess bleeding risk before initiating aspirin
3. Neglecting iron deficiency: Repeated phlebotomies can lead to iron deficiency, which may paradoxically increase blood viscosity despite lower hematocrit
4. Overuse of cytoreductive therapy: Reserve for high-risk patients or those with specific indications
5. Inadequate monitoring: Regular follow-up is essential to detect complications early

The management of polycythemia vera requires a systematic approach focusing on thrombosis prevention while minimizing treatment-related complications. While no current medications cure the disease or reduce the risk of transformation to leukemia or myelofibrosis, proper management significantly improves quality of life and survival 4.