What is Polycythemia Vera (PV) characterized by?

Characteristics of Polycythemia Vera

Polycythemia vera is characterized by accelerated erythropoiesis and excessive proliferation of myeloid and megakaryocytic elements of the bone marrow. 1

Pathophysiological Features

Polycythemia vera (PV) is a clonal stem cell disorder with distinct pathological characteristics:

• Trilineage myeloid involvement with predominant erythrocytosis 2

• Bone marrow hypercellularity with characteristic changes including:

  • Increased number of megakaryocytes with cluster formation
  • Presence of giant megakaryocytes and pleomorphic megakaryocyte morphology
  • Mild reticulin fibrosis (in approximately 12% of patients)
  • Decreased bone marrow iron stores 1

• Molecular basis:

  • JAK2 mutation present in >95% of patients 3
  • The JAK2V617F mutation is associated with constitutive activation of signaling pathways 4
  • Abnormal karyotype in 13-18% of patients at diagnosis 1

Clinical and Laboratory Features

PV manifests with several characteristic findings:

• Hematological abnormalities:

  • Erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) 3
  • Thrombocytosis (present in 53% of patients) 3
  • Leukocytosis (present in 49% of patients) 3

• Growth factor independence:

  • Erythroid progenitor cells demonstrate EPO-independent growth 1
  • Decreased expression of thrombopoietin receptor (c-mpl) 1
  • Elevated or normal plasma thrombopoietin levels despite increased megakaryocyte/platelet mass 1

• Clinical manifestations:

  • Splenomegaly (36% of patients) 3
  • Pruritus, especially after warm showers (33% of patients) 2, 3
  • Erythromelalgia (5.3% of patients) 3
  • Transient visual changes (14% of patients) 3

Diagnostic Approach

The diagnosis of PV requires:

1. Erythrocytosis: Hemoglobin >16.5 g/dL in men or >16.0 g/dL in women 3
2. JAK2 mutation testing: Present in >95% of PV patients 3
3. Bone marrow examination: Shows hypercellularity with trilineage involvement 1
4. Serum erythropoietin level: Typically low in PV 1

Complications and Prognosis

PV is associated with significant complications:

• Thrombotic events: 16% arterial and 7% venous thrombosis at or before diagnosis 3
• Disease transformation:
  • Myelofibrosis develops in 12.7% of patients 3
  • Acute myeloid leukemia occurs in 6.8% of patients 3
• Median survival: 14.1 to 27.6 years from diagnosis 3

Management Principles

Treatment goals focus on reducing complications:

• Phlebotomy: Cornerstone treatment to maintain hematocrit <45% 2
• Low-dose aspirin: For all patients without contraindications 3
• Cytoreductive therapy: For high-risk patients (age ≥60 years or prior thrombosis) 3
  • First-line options: Hydroxyurea or interferon 5
  • Second-line options: Ruxolitinib for those intolerant to hydroxyurea 3

Important Distinctions

PV must be distinguished from:

• Secondary causes of erythrocytosis (smoking, sleep apnea, high altitude) 3
• Other myeloproliferative neoplasms (essential thrombocythemia, primary myelofibrosis) 4

The presence of accelerated erythropoiesis with concurrent proliferation of myeloid and megakaryocytic elements is the pathological hallmark that distinguishes PV from other conditions with isolated erythrocytosis or other lineage abnormalities.