Overview

Also known as polycythaemia rubra vera, polycythaemia vera (PV) is a myeloproliferative disorder characterised by the excess production of red blood cells. This leads to the blood becoming thicker and increases the risk of thrombosis. It often has associated overproduction of neutrophils and platelets.

PV can progress to secondary myelofibrosis (MF). Over 90% of patients with PV have a mutation in JAK2.

Pathophysiology

PV occurs due to excess proliferation and maturation of myeloid precursor cells that normally lead to the development of red blood cells, granulocytes, and platelets. JAK2 is involved in the signalling pathways of the erythropoietin (EPO) receptor. Mutations in JAK2 lead to proliferation without the need for EPO.

Epidemiology

  • Incidence of 2 per 100,000 per year
  • Peak incidence >65 years of age

Risk Factors

Example History

A 65-year-old man comes to the GP with whole-body itching after showering. He has had fatigue over the last year. On examination, he appears plethoric and the spleen is palpable 4cm below the costal angle.

 Investigations:

Haemoglobin:195 g/L(130 – 180 g/L)
Platelets:370 x 109/L(150 – 450 x 109/L)
White blood cells:8.0 x 109/L(3.0 – 10.0 x 109/L)

Presentation

Patients often present with a plethoric (ruddy and red-ish) complexion with features of thrombosis. Features are:

  • Plethora and facial redness
  • Pruritus – typically after a hot bath or shower
    • This is thought to be due to abnormal histamine release
  • Erythromelalgia – burning and/or redness of the fingers/hands/heels/toes
    • Due to aggregation of platelets forming small thrombi in the blood vessels of the extremities
  • Weakness and fatigue
  • Splenomegaly
    • Due to increased sequestration of cells as there are more present 
  • Features of thrombosis e.g. previous stroke, myocardial infarction, Budd-Chiari syndrome, deep vein thrombosis, pulmonary embolism etc.

Differential Diagnoses

Haemochromatosis

Investigations

All patients

  • Full blood count (FBC) and white cell differential:
    • Haemoglobin: raised
      • This is not specific, as chronic hypoxia and exogenous testosterone can cause polycythaemia
    • Haematocrit: raised
    • Mean cell volume (MCV): usually low but can be normal
    • White cell count: usually elevated
    • Platelets: usually elevated
  • Serum ferritin:
    • Screens for iron deficiency or other iron-related disorders (e.g. haemochromatosis)
    • Normal
  • Liver function tests (LFTs):
    • Usually normal – screens for Budd-Chiari syndrome and haemochromatosis
  • JAK2 gene mutation screen:
    • JAK2 V617F mutation is usually present

Diagnosis

The World Health Organisation has produced diagnostic criteria for PV involving the use of features which are classed as ‘major’ and ‘minor’ criteria.

Management

Overview

  • 1st-line: regular venesection and aspirin
    • Regular venesection keeps haemoglobin in the normal range
    • Aspirin reduces the risk of thrombotic events
  • Chemotherapies such as hydroxyurea are considered

Complications

  • Progression to myelofibrosis
  • Progression to acute myeloid leukaemia (AML)
  • Thrombotic events e.g. stroke, myocardial infarction, venous thromboembolism etc.

Prognosis

  • Without treatment, life expectancy is 6-18 months
  • Median survival is around 14 years
  • The most common causes of death are ischaemic stroke and myocardial infarction

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