Essential thrombocythaemia and myelofibrosis

Essential thrombocythaemia

Essential thrombocythaemia (ET) is a chronic myeloproliferative neoplasm characterised by a persistent increase in platelet count. It is thought to be a clonal stem cell disorder although recent studies suggest that it is heterogeneous. Almost half of ET patients are positive for the JAK2 V617F mutation (see p. 64). They appear to have distinct clinical features including a closer link to polycythaemia vera and a higher incidence of thrombosis. ET may be associated with either thrombotic or haemorrhagic complications, the latter caused by abnormal platelet function. The average age of presentation is around 60 years. The prognosis is generally good although there is a risk of transformation to myelofibrosis, polycythaemia and acute myeloid leukaemia.

Clinical features

ET may be asymptomatic and discovered accidentally on routine blood testing. Symptoms commonly arise from disturbances of the microcirculation. Patients may complain of burning sensations in the soles and palms, cold peripheries and varied neurological symptoms including headache and dizziness. Arteriolar occlusion can cause ischaemia, gangrene or acrocyanosis. Thrombosis of large arteries is of even greater concern. Haemorrhagic problems are less common but include ecchymoses, epistaxis, menorrhagia and bleeding into the mouth and gut. Splenomegaly is unusual at least in part because of splenic infarction, which can be painful.

Platelet counts can be as high as 2000 × 10⁹/L and usually exceed 450 × 10⁹/L (the normal range is 150–400 × 10⁹/L) (Fig 33.1). In practice, there is no single test to specifically identify ET – diagnosis is often a process of exclusion. As thrombocytosis may accompany a wide range of disorders including infections, inflammatory conditions, malignancy and iron deficiency, a thorough history and examination is mandatory. The lack of a measurable ‘acute phase response’ (i.e. normal erythrocyte sedimentation rate, plasma viscosity and fibrinogen) increases the likelihood of ET as opposed to a ‘reactive’ thrombocytosis. Even where there is an acquired JAK2 gene mutation, other myeloproliferative disorders must be excluded. Bone marrow examination is worthwhile to exclude chronic myeloid leukaemia (absence of Philadelphia chromosome), myelofibrosis or myelodysplasia, and to check iron stores. Patients with polycythaemia vera may have thrombocytosis, while patients with ET can have an increased red cell mass. In practice such patients are better diagnosed as having myeloproliferative neoplasms rather than forced into either category. Only about 5% of all raised platelet counts are due to ET, but persistence of the count above 1000, particularly with coexistence of thrombosis or haemorrhage, makes it the likely diagnosis. Abnormal platelet function tests suggest ET rather than a reactive thrombocytosis.