What are the implications of polycythemia?

Implications of Polycythemia (RBC Count 5.5)

An elevated red blood cell count of 5.5 indicates polycythemia, which significantly increases the risk of thrombotic complications including stroke, myocardial infarction, and venous thromboembolism, and requires prompt management to reduce morbidity and mortality. 1

Types and Diagnosis

Polycythemia can be classified as:

1. Primary (Polycythemia Vera)

   • Clonal myeloproliferative neoplasm
   • JAK2 mutation present in >95% of cases
   • Low or normal serum erythropoietin levels typically (though can rarely be elevated) 2
   • Diagnostic criteria include elevated hemoglobin/hematocrit plus JAK2 mutation 1

2. Secondary Polycythemia

   • Due to increased erythropoietin production
   • Causes include:
     • Chronic hypoxia (COPD, sleep apnea)
     • Renal disease
     • Cyanotic heart disease
     • High altitude
     • Smoking
     • Androgen use 3

Clinical Manifestations

• Thrombotic events (26% 20-year risk in PV) 4

  • Arterial thrombosis (stroke, MI)
  • Venous thrombosis (DVT, PE, splanchnic vein thrombosis)
  • Microvascular disturbances

• Neurological manifestations

  • Headache
  • Dizziness
  • Visual disturbances (14% of patients) 5
  • Stroke or TIA
  • Confusion

• Other symptoms

  • Pruritus (33-48% of patients) 1, 5
  • Erythromelalgia (painful burning of extremities) in 3-5.3% 1, 5
  • Splenomegaly (36% of patients) 5
  • Facial plethora
  • Hyperviscosity symptoms

Risk Stratification

For polycythemia vera, patients are stratified into:

• High risk: Age >60 years and/or history of thrombosis
• Low risk: Absence of both risk factors 1, 4

Management Approach

1. For all patients with polycythemia vera:

   • Therapeutic phlebotomy to maintain hematocrit <45% 1, 5, 4
   • Low-dose aspirin (81-100 mg daily) unless contraindicated 1
   • Address cardiovascular risk factors

2. For high-risk patients or symptomatic low-risk patients:

   • Cytoreductive therapy with:
     • Hydroxyurea (first-line)
     • Interferon-α (alternative first-line, especially in younger patients)
     • Ruxolitinib (for hydroxyurea resistance/intolerance)
     • Busulfan (in older patients) 1, 6, 4

3. For secondary polycythemia:

   • Treat underlying cause
   • Judicious phlebotomy to hematocrit 55-60% for COPD or cyanotic heart disease 3
   • Consider ACE inhibitors for post-renal transplant erythrocytosis 3

Monitoring and Complications

• Regular CBC monitoring (every 2-3 months initially, then every 3-6 months when stable) 1
• Watch for disease progression:
  • Myelofibrosis (12.7-16% risk over 20 years) 5, 4
  • Acute myeloid leukemia (4-6.8% risk over 20 years) 5, 4
• Monitor for bleeding complications, especially with extreme thrombocytosis 5

Important Pitfalls to Avoid

1. Overzealous phlebotomy in secondary polycythemia from cyanotic heart disease or COPD can increase stroke risk 3

2. Overlooking masked PV due to iron deficiency from repeated phlebotomies 1

3. Missing secondary causes when JAK2 mutation is absent 1

4. Neglecting bone marrow examination for morphologic confirmation in suspected PV 1

5. Failing to address pruritus, which can significantly impact quality of life 1

The elevated RBC count requires thorough evaluation to determine whether it represents primary or secondary polycythemia, as management approaches differ significantly based on etiology, with the primary goal being prevention of thrombotic complications that can lead to significant morbidity and mortality.