• Clinical science

Polycythemia vera

Summary

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is characterized by an erythropoietin-independent, irreversible increase in erythrocyte, granulocyte, and platelet counts. The elevated blood cell mass results in hyperviscosity, which is associated with slow blood flow and an increased risk of thrombosis. . The disorder typically initially has a long asymptomatic period, then assumes a chronic, insidious course. Clinical features include facial flushing, pruritus, erythromelalgia, headaches, and dizziness. Severe complications such as thrombotic events (e.g., stroke, Budd-Chiari syndrome) may occur. Since PV is an incurable disorder, the primary goals of management involve controlling RBC mass and reducing the risk of thrombotic complications. Periodic phlebotomy reduces the amount of circulating cells and is therefore the treatment of choice.

Pathophysiology


References:[1][2][3]

Clinical features

  • Often asymptomatic (incidental finding on routine blood tests!)
  • Constitutional symptoms: weight loss, fatigue, sweating
  • Hyperviscosity syndrome (triad of mucosal bleeding, neurological symptoms, and visual changes)
  • Plethora
    • Facial flushing
    • Cyanotic lips
  • Pruritus: Itching typically worsens when the skin comes into contact with warm water (aquagenic pruritus).
  • Nonspecific neurological symptoms : dizziness, headache, visual disturbances, tinnitus
  • Hypertension
  • Splenomegaly : associated with early satiety and abdominal discomfort; less commonly hepatomegaly
  • Peptic ulcer disease
  • Symptoms of thrombotic and hemorrhagic complications (see “Complications” below)

Patients with PV are at increased risk of thrombosis and bleeding!
References:[2][4][5][6][7][8]

Diagnostics

Laboratory findings

Diagnostic criteria (WHO 2016) [9][10]

A diagnosis of polycythemia vera requires:

  • All three major criteria
    OR
  • The first two major criteria AND the minor criterion
Major criteria
  1. Evidence of increased RBCs
  2. Bone marrow biopsy showing hypercellularity with trilineage growth (increased erythropoiesis, granulopoiesis, and megakaryopoiesis)
  3. Evidence of a genetic mutation in the JAK2 gene
Minor criterion
  • ↓ EPO levels

References:[2][11][12]

Differential diagnoses

Secondary erythrocytosis

EPO Expected plasma volume RBC mass Oxygen saturation Underlying conditions
Relative polycythemia ↔︎ ↓ ↔︎ / ↑ ↔︎
Appropriate absolute polycythemia ↑ ↔︎ ↑ ↓
  • High-altitude exposure
  • Hypoxia: chronic pulmonary and cardiac disease
Inappropriate absolute polycythemia ↑↑ ↔︎ ↑ ↔︎
  • Other causes may present with normal or even decreased endogenous EPO levels.

References:[13]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Phlebotomy: Periodic phlebotomy temporarily reduces cell counts and hyperviscosity.
    • 250–500 mL in intervals of 2–3 days until a HCT of ≤ 0.45 is established[14]
      • The need for phlebotomy depends on HCT levels.
        • Iron deficiency is intentionally induced.
        • Iron substitution is only indicated if the patient displays obvious symptoms.
        • Alternative: erythrocytapheresis
        • Contraindications
  • Antiplatelet prophylaxis: aspirin
  • Cytoreductive therapy: determined on an individual basis; recommended if risk factors are present

If platelet count is > 1 million/μL, platelet function is very likely to be impaired, and the risk of bleeding is significantly increased. Aspirin should be discontinued!
References:[15][16][14]

Complications

Polycythemia vera is a life-threatening disease because of the numerous complications associated with it.

Thrombotic complications

Hemorrhagic complications

Late stages

References:[2][4][10][16]

We list the most important complications. The selection is not exhaustive.