23rd July 2024

Polycythaemia vera (PV)

Background of PV

PV is a true primary erythrocytosis from clonal proliferation of haematopoietic stem cells, as opposed to a secondary erythrocytosis such as from hypoxia or a relative erythrocytosis from reduced plasma volume.

Median age at diagnosis is ~60 years with a slight male predominance.

JAK2 mutations are associated with almost all cases of PV. The majority of these exhibit the V617F mutation on exon 14 of the JAK2 gene; more rarely there are mutations on exon 12.

Presentation and diagnosis of PV

Most patients are identified incidentally with an elevated haemoglobin or haematocrit.

Common presenting complaints include aquagenic pruritus (pruritus after a warm bath or shower) and erythromelalgia (red, painful extremities). Arterial or venous thrombosis (stroke, myocardial infarction, deep vein thrombosis) and haemorrhage (intracranial or gastrointestinal) can occur. Hyperviscosity symptoms may be present (headache, visual disturbance, fatigue).

Signs include facial plethora (ruddy complexion), gouty arthritis, splenomegaly and hypertension.

Diagnosis:

• Bloods: full blood count (erythrocytosis, raised haematocrit and red cell mass, thrombocytosis and neutrophilia are common)
• JAK2 mutation analysis

If haematocrit (or red cell mass) is raised and JAK2 mutations are present, this is sufficient for diagnosis. If the patient is JAK2 mutation negative, then further investigations including serum erythropoietin (normal or low in PV, raised in patients with secondary polycythaemia), bone marrow biopsy and ultrasound imaging may be necessary.

Management and prognosis of PV

Treatment is not curative; aims are to reduce plasma viscosity, aiming for a haematocrit <0.45, and reduce thrombosis risk. All patients should be given advice on managing other cardiovascular risk factors.

Plasma viscosity is reduced with regular venesection and cytoreductive therapy (e.g. hydroxycarbamide).

Thrombosis risk is reduced with regular low-dose aspirin.

PV may progress to PMF (spent-phase PV, 10-15% after 10 years) or transform to MDS or AML. Occurrence of these confers a poor prognosis.

Median survival in untreated symptomatic patients is ~18 months. Treatment extends median survival to >13 years.