Polycythaemia vera (PV)

PV is a myeloproliferative neoplasm; other diseases in this category are essential thrombocythaemia and myelofibrosis (see p. 66). In PV a pluripotential stem cell is mutated. Almost all patients with the disease (and some with essential thrombocythaemia and myelofibrosis) have an identical acquired point mutation in the Janus kinase 2 (JAK2) gene.

Clinical features. The raised red cell mass and total blood volume with associated hyperviscosity causes the symptoms and signs of the disease. Common complaints include headaches, dizziness, lethargy, sweating and pruritus (the latter particularly after a hot bath). Most importantly, there is an increased risk of arterial and venous thrombosis, particularly strokes. Paradoxically, a combination of hyperviscosity and platelet dysfunction may cause a bleeding tendency. The increased cell turnover can lead to gout (Fig 32.3). Patients are characteristically plethoric and may have rosacea (Fig 32.4). Palpable splenomegaly may be present.

Diagnosis. The diagnostic challenge is to differentiate PV from a secondary polycythaemia. Splenomegaly and elevated white cell and platelet counts are suggestive of PV. Increased erythropoiesis can lead to iron deficiency. Erythropoietin estimation by radioimmunoassay is normal or low. The bone marrow aspirate and trephine in PV show hypercellularity but there may be no pathognomonic features. Testing for the JAK2 V617F mutation is now central to the diagnosis of PV (Table 32.1). Around 95% of patients with PV are positive. In the rare negative PV cases, mutations in exon 12 of JAK2 have been found. It is likely that other genetic events (e.g. MPL, TET2 mutations) are required for disease development.

Management. The dual purpose of treatment is to relieve symptoms and to reduce the risk of complications such as thrombotic disease and bleeding. Aspirin (75 mg/day) should be given unless contraindicated. The PCV is reduced below 0.45 by venesections (up to 450 mL of blood removed) which may initially be required twice weekly. In more severe disease the need for venesection can become intolerable and cytotoxic drugs are used to suppress erythropoiesis. Hydroxycarbamide is the usual choice. Interferon alfa can be useful in younger patients and in pregnancy. Busulfan is effective given intermittently but is best limited to older patients as there is a significant risk of secondary malignancy. Drug treatment is particularly important when there is a need to control coexistent thrombocytosis or progressive splenomegaly. JAK2 inhibitors are under investigation.

PV is a relatively benign disorder and if well controlled is compatible with a median survival of greater than 10 years. However, it is a clonal disease and a few patients eventually transform to myelofibrosis (10%) or even acute leukaemia (5%). The risk of the latter is increased by treatment with alkylating agents.

Secondary polycythaemia

This is due to either a physiological response to hypoxia or an inappropriate secretion of erythropoietin. Causes are numerous and are listed in Table 32.2 (and see Fig 32.5). Treatment is essentially that of the underlying cause, although cases with very high PCVs may benefit from venesection.

Idiopathic erythrocytosis

This is a small heterogeneous group of patients who have an absolute polycythaemia without features of either PV or secondary polycythaemia. Venesection may be required.

Apparent polycythaemia

This condition has accumulated several names including spurious, stress or relative polycythaemia, pseudopolycythaemia and Gaisbock’s syndrome. The usual cause is an increase in red cell mass and a decrease in plasma volume within the normally accepted limits (see Fig 32.1). Patients are most frequently male and middle-aged. Other common characteristics are excess weight, hypertension, diuretic use and significant consumption of alcohol and tobacco. The adoption of a healthier lifestyle often leads to resolution of polycythaemia. Venesection is not routine but is considered where there are thrombotic risk factors.