Essential Thrombocythemia

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm with sustained thrombocytosis (platelets 450 x 10^9/L or more) and megakaryocyte proliferation.

• Incidence 1 to 2.5 per 100,000, median age 60 with a second peak in young women.

• Driver mutations: JAK2 V617F (55%), CALR (25%), MPL (3%), triple negative (15%).

• Complications: arterial and venous thrombosis (including splanchnic), microvascular symptoms (erythromelalgia), bleeding with platelets over 1000 (acquired von Willebrand), transformation to myelofibrosis (10% at 15 years) or AML (under 5%), pregnancy loss.

• Risk groups (IPSET-thrombosis): very low, low, intermediate, high based on age over 60, prior thrombosis, JAK2 mutation, cardiovascular risk factors.

• Often asymptomatic.

• Headache, visual disturbance, dizziness, erythromelalgia, transient ischaemic attacks, thrombosis, mild splenomegaly.

• Bleeding mainly mucosal.

• Persistent thrombocytosis, normal haemoglobin and white count.

• JAK2, CALR and MPL testing; bone marrow biopsy showing enlarged mature megakaryocytes, no significant fibrosis or left shift.

• Exclude reactive thrombocytosis (iron deficiency, infection, inflammation, cancer, splenectomy), CML (BCR-ABL1), polycythaemia vera, myelofibrosis, MDS with del5q.

• Von Willebrand testing if platelets over 1000.

• Aspirin 81 to 100 mg daily (twice daily in selected JAK2/CALR patients with microvascular symptoms) for intermediate and high risk, and low risk with cardiovascular risk factors or JAK2.

• Cytoreduction for high risk (age over 60, prior thrombosis, platelets over 1500): hydroxyurea 15 to 20 mg/kg/day titrated to platelets under 400 and white count above 2.5; anagrelide 0.5 mg twice daily increasing to 2 mg twice daily (cardiac monitoring; second line); ropeginterferon alfa-2b 50 to 100 micrograms every 2 weeks (preferred in under 40 and pregnancy planning).

• Ruxolitinib for hydroxyurea resistant disease.

• Control cardiovascular risk factors, stop smoking.

• Pregnancy: low dose aspirin, LMWH for prior thrombosis or complications, interferon alfa if cytoreduction needed; avoid hydroxyurea and anagrelide.

• Surgery: delay elective surgery until platelets controlled; thromboprophylaxis.

• Monitor blood counts every 3 months; consider marrow if cytopenias or splenomegaly develop.