What are the key differences in diagnosis and management between polycythemia (PCV) and essential thrombocytosis (ET)?

Key Differences in Diagnosis and Management Between Polycythemia Vera and Essential Thrombocythemia

The primary diagnostic difference between polycythemia vera (PV) and essential thrombocythemia (ET) is that PV is characterized by erythrocytosis while ET is defined by thrombocytosis, with each requiring distinct diagnostic criteria and management approaches. 1

Diagnostic Criteria

Polycythemia Vera (PV)

• Major criteria:
  • Elevated hemoglobin (>18.5 g/dL in men, >16.5 g/dL in women) or increased red cell mass
  • Presence of JAK2 V617F or similar mutation (e.g., JAK2 exon 12)
• Minor criteria:
  • Bone marrow showing hypercellularity with trilineage growth
  • Subnormal serum erythropoietin level
  • Endogenous erythroid colony formation

Diagnosis requires both major criteria or the first major criterion plus two minor criteria 1

Essential Thrombocythemia (ET)

• Requires meeting all four criteria:
  1. Sustained platelet count ≥450 × 10^9/L
  2. Bone marrow biopsy showing megakaryocytic proliferation with mature megakaryocytes
  3. Not meeting criteria for other myeloid neoplasms (PV, PMF, CML, MDS)
  4. JAK2, CALR, or MPL mutation or no evidence of reactive thrombocytosis 1, 2

Key Distinguishing Features

Molecular Profile

• PV: Almost all patients (>95%) have JAK2 mutations (mostly V617F, some exon 12)
• ET: Approximately 60% have JAK2 V617F, 25% have CALR mutations, and 3% have MPL mutations 3, 4

Bone Marrow Morphology

• PV: Hypercellular marrow with trilineage growth (panmyelosis)
• ET: Proliferation mainly of megakaryocytic lineage with enlarged, mature megakaryocytes with deeply lobulated nuclei 1

Exclusionary Testing

• For PV: Normal or increased serum erythropoietin level excludes PV
• For ET: Must exclude reactive thrombocytosis, PV, prefibrotic myelofibrosis, and CML 1, 2

Risk Stratification

Polycythemia Vera

• High risk: Age >60 years OR history of thrombosis
• Low risk: Absence of both risk factors 3, 5

Essential Thrombocythemia

• Very low risk: Age ≤60 years, no thrombosis history, JAK2 wild-type
• Low risk: Age ≤60 years, no thrombosis history, JAK2 mutation present
• Intermediate risk: Age >60 years, no thrombosis history, JAK2 wild-type
• High risk: Thrombosis history OR age >60 years with JAK2 mutation 3

Management Approaches

Polycythemia Vera

1. All patients:

   • Phlebotomy to maintain hematocrit <45%
   • Low-dose aspirin (81 mg once or twice daily)

2. High-risk patients:

   • Cytoreductive therapy with hydroxyurea as first-line
   • Interferon-α or busulfan as second-line options 3, 5

Essential Thrombocythemia

1. Very low risk: Observation may be sufficient
2. Low risk: Low-dose aspirin
3. Intermediate risk: Consider cytoreductive therapy based on additional risk factors
4. High risk: Cytoreductive therapy with hydroxyurea as first-line
   • Interferon-α or busulfan as second-line options 3, 5

Special Considerations

• Extreme thrombocytosis (>1,000 × 10^9/L) in either condition may be associated with acquired von Willebrand syndrome and increased bleeding risk 6, 4
• JAK2 mutation in ET is associated with higher thrombosis risk 3, 5
• Leukocytosis is a risk factor for poor outcomes in both conditions 6, 4
• 10-year risk of leukemic transformation is <1% in ET and approximately 3% in PV 3, 5

Follow-up Recommendations

• PV: Every 2-4 months for phlebotomy needs; 4-6 months if stable on cytoreduction
• ET: Every 6-12 months for low-risk; every 3-4 months for high-risk on cytoreduction 1

Treatment Response Evaluation

Treatment response should be assessed using the European LeukemiaNet criteria, which evaluate resolution of disease-related signs, normalization of blood counts, and bone marrow histological remission 1.