Introduction

Polycythaemia vera (previously called polycythaemia rubra vera) is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has recently been established that a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera and this has resulted in significant changes to the diagnostic criteria. The incidence of polycythaemia vera peaks in the sixth decade.

Epidemiology

  • Incidence: 2.00 cases per 100,000 person-years
  • Peak incidence: 60-70 years
  • Sex ratio: 1:1
Condition Relative
incidence
Polycythaemia vera1
Chronic myeloid leukaemia0.50
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Clinical features

Features
  • Hyperviscosity
  • Pruritus, typically after a hot bath
  • Splenomegaly
  • Haemorrhage (secondary to abnormal platelet function)
  • Plethoric appearance
  • Hypertension in a third of patients

Investigations

Following history and examination, the British Committee for Standards in Haematology (BCSH) recommend the following tests are performed
  • Full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients)
  • JAK2 mutation
  • Serum ferritin
  • Renal and liver function tests

If the JAK2 mutation is negative and there is no obvious secondary causes the BCSH suggest the following tests:
  • Red cell mass
  • Arterial oxygen saturation
  • Abdominal ultrasound
  • Serum erythropoietin level
  • Bone marrow aspirate and trephine
  • Cytogenetic analysis
  • Erythroid burst-forming unit (BFU-E) culture

Other features that may be seen in PRV include a low ESR and a raised leukocyte alkaline phosphatase

Diagnosis

The diagnostic criteria for polycythaemia vera have recently been updated by the BCSH. This replaces the previous polycythaemia vera Study Group criteria.

JAK2-positive polycythaemia vera - diagnosis requires both criteria to be present

CriteriaNotes
A1High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)
A2Mutation in JAK2

JAK2-negative PRV - diagnosis requires A1 + A2 + A3 + either another A or two B criteria

CriteriaNotes
A1Raised red cell mass (>25% above predicted) OR haematocrit >0.60 in men, >0.56 in women
A2Absence of mutation in JAK2
A3No cause of secondary erythrocytosis
A4Palpable splenomegaly
A5Presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cells
B1Thrombocytosis (platelet count >450 * 109/l)
B2Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers)
B3Radiological evidence of splenomegaly
B4Endogenous erythroid colonies or low serum erythropoietin

Management

Polycythaemia vera is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly

Management
  • Aspirin
  • Venesection - first line treatment
  • Hydroxyurea -slight increased risk of secondary leukaemia
  • Phosphorus-32 therapy

Prognosis

Prognosis
  • Thrombotic events are a significant cause of morbidity and mortality
  • 5-15% of patients progress to myelofibrosis
  • 5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)