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Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN, see this term) characterized by a sustained elevation of platelet number (> 450 x 109/L) with a tendency for thrombosis and hemorrhage.
ORPHA:3318Classification level: Disorder
Prevalence is estimated at 1/4,200 in the US and is reported at 1/3,333 in Sweden. Median age at diagnosis is 60-65 years, but the disease may occur at any age, with another peak in incidence in younger women. The female to male ratio is about 2:1.
The clinical picture is dominated by a predisposition to vascular occlusive events and hemorrhages. Some patients with ET are asymptomatic, while others may experience microcirculatory disturbances or vasomotor events: headaches, visual disturbances, lightheadedness, atypical chest pain, distal paresthesias, erythromelalgia, and other symptoms of transient neurological ischemia. Less frequently ET is associated with an increased risk of hemorrhage. Main risks for patients include thromboses (arterial and venous), which can induce severe neurological, cardiac or peripheral artery manifestations. Transformation to myelofibrosis (see this term) or acute leukemia is possible in a small proportion of patients on the long term.
Somatic mutations in the JAK2 gene are the most common genetic alterations found in ET. Mutations in LNK gene down regulate JAK2 pathway and can be causative. Mutations in MPL gene has also been found in cases of ET with myeloproliferation. Recently mutations in CALR have been identified in many patients who were negative for JAK2 and MPL. The detailed pathogenic mechanism is unknown. Although ET is usually an acquired (non hereditary) disease, a familial form, primary familial thrombocytosis (see this term) has also been observed.
Diagnosis is based on a sustained high level of platelets (over 450x109/L) in the absence of reactive causes (like iron deficiency or inflammation, see below), evidence of a clonal marker (somatic mutation in JAK2, CALR , MPL or other genes involved in MPN pathogenesis), bone marrow showing increased megakaryocytes with large and mature morphology with no increase in reticulin and an absence of MPN among relatives to rule out primary familial polycythemia (see this term).
Differential diagnoses include the other myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis, chronic myeloid leukemia; see these terms), myeloid malignancies (myelodysplastic syndrome), causes of secondary thrombocytosis (inflammation, cancer, iron deficiency, asplenia) and primary familial thrombocytosis (see this term).
Management and treatment
Management is currently based on the risk of thrombosis, and may involve anti-aggregation therapy and/or platelet cytoreduction. Hydroxycarbamide and aspirin are effective in high risk patients. Anagrelide is approved in European Union as platelet lowering agent in patients resistant or intolerant to hydroxycarbamide. Conventional and pegylated recombinant interferon alpha (IFN) are effective in controlling platelet counts, although there is no evidence of efficacy in preventing thrombosis and could be preferred to conventional cytoreductive therapies in younger patients. Risk factors associated with arteriosclerotic disease (hypertension, diabetes, smoking etc) must be actively managed. Conventional cytoreductive therapies are contra-indicated in pregnancy.
Overall survival is similar to that of a healthy population matched by age and sex during the first decade after diagnosis and may differ thereafter (due to disease complications such as thrombosis, transformation to myelofibrosis, acute leukemia or myelodysplasia). When properly managed and carefully followed, life expectancy of ET patients can be similar to that of general population.
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