{"entity":{"id":"essential-thrombocythaemia","kind":"cancer","name":"Essential thrombocythaemia (ET)","aka":["Essential thrombocythemia","ET","Primary thrombocythaemia","Essential thrombocytosis"],"tldr":"Essential thrombocythaemia is a slow blood cancer in which the marrow makes too many platelets. Most people need only aspirin and monitoring; those at higher risk of clots take a drug to lower the platelet count, usually hydroxyurea or interferon, with anagrelide in reserve.","summary":"Essential thrombocythaemia is a classical myeloproliferative neoplasm defined by a sustained platelet count above 450 x 10^9/L with a marrow full of large, mature megakaryocytes and no other explanation. About 60 percent carry JAK2 V617F, 20 to 25 percent a CALR mutation and 3 to 5 percent an MPL mutation; the rest are triple negative. Many people have no symptoms and are found on a routine blood count; others have headaches, visual disturbance, burning red hands and feet (erythromelalgia) or, at high platelet counts, paradoxical bleeding. Treatment is set by the IPSET-thrombosis score, which weighs age, prior clot, JAK2 status and cardiovascular risk: very low-risk patients may need nothing, low-risk patients take low-dose aspirin, and high-risk patients add cytoreduction with hydroxyurea or interferon, with anagrelide second line. The PT-1 trial showed hydroxyurea plus aspirin beats anagrelide plus aspirin on arterial clots and bleeding. Progression to myelofibrosis happens in a minority over decades and to acute leukaemia in a few percent. Bomedemstat, an LSD1 inhibitor, is in a phase 3 trial against hydroxyurea, and antibodies against mutant CALR are the first treatments aimed at the clone itself.","asOf":"2026-09-16","wikipedia":"https://en.wikipedia.org/wiki/Essential_thrombocythemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Essential_thrombocythemia"},{"label":"MPN Research Foundation","url":"https://www.mpnresearchfoundation.org/essential-thrombocythemia/"}],"tags":["essential-thrombocythaemia","mpn"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"group":"haematologic","burden":"Around one to two new cases per 100,000 people a year, with a second peak in women in their thirties; life expectancy is close to normal for most, and the risks are clots, bleeding and slow progression to myelofibrosis.","subtypes":["JAK2 V617F-mutated (about 60 percent; higher thrombosis risk)","CALR-mutated (20 to 25 percent; higher platelets, lower thrombosis risk)","MPL-mutated (3 to 5 percent)","Triple negative (10 to 15 percent)","Prefibrotic primary myelofibrosis (a look-alike separated by marrow histology since WHO 2016)"],"biomarkers":["Platelet count above 450 x 10^9/L","JAK2 V617F, CALR exon 9 and MPL W515 mutations","IPSET-thrombosis score (age over 60, prior thrombosis, JAK2 V617F, cardiovascular risk factors)","Marrow histology to exclude prefibrotic myelofibrosis","Acquired von Willebrand deficiency at platelet counts above 1,000 x 10^9/L (bleeding risk with aspirin)"],"standardOfCare":[{"setting":"Diagnosis","approach":"Full blood count, JAK2, CALR and MPL testing, bone marrow biopsy to confirm ET and exclude prefibrotic myelofibrosis, and exclusion of reactive causes (iron deficiency, inflammation, infection, splenectomy).","refs":["jak2","jak2-v617f","myeloproliferative-neoplasms"]},{"setting":"Very low and low risk","approach":"Observation alone in very low risk (under 60, no clot, JAK2-negative); low-dose aspirin for low risk and for anyone with microvascular symptoms, once acquired von Willebrand deficiency is excluded at very high platelet counts.","refs":["aspirin","erythromelalgia"]},{"setting":"High risk (over 60 with JAK2 or prior clot)","approach":"Cytoreduction to a platelet count under 400 x 10^9/L: hydroxyurea first line (PT-1), pegylated or ropeginterferon alfa-2b preferred under 60 and in pregnancy, anagrelide second line.","refs":["hydroxyurea","pt-1","ropeginterferon-alfa-2b","anagrelide"]},{"setting":"Hydroxyurea resistance or intolerance","approach":"Switch to interferon or anagrelide; ruxolitinib did not beat best available therapy in MAJIC-ET but relieves symptoms.","refs":["anagrelide","ruxolitinib","majic-et"]},{"setting":"Progression to myelofibrosis","approach":"Managed as myelofibrosis: JAK inhibitors for spleen and symptoms, transplant for fit higher-risk patients.","refs":["myeloproliferative-neoplasms","post-pv-myelofibrosis","ruxolitinib"]}],"stateOfArt":["Most people with ET live a near-normal lifespan; the treatment question is who needs more than aspirin, and IPSET-thrombosis answers it better than platelet count alone.","Hydroxyurea remains first line for high-risk disease because PT-1 showed fewer arterial clots and less bleeding than anagrelide.","Interferons give molecular responses in JAK2- and CALR-mutated ET and are the choice in younger patients and pregnancy.","Bomedemstat is the first new cytoreductive drug in a phase 3 trial against hydroxyurea in two decades.","Mutant-CALR antibodies (INCA033989 and others) are the first treatments that target the ET clone itself, in early trials."],"history":[{"year":1934,"title":"Epstein and Goedel describe haemorrhagic thrombocythaemia","note":"The first account of a primary platelet disorder with bleeding and clotting.","refs":[]},{"year":1951,"title":"Dameshek groups the myeloproliferative disorders","refs":["myeloproliferative-neoplasms"]},{"year":2005,"title":"JAK2 V617F found in half of ET","refs":["jak2-v617f"]},{"year":2005,"title":"PT-1: hydroxyurea beats anagrelide","note":"In 809 high-risk patients hydroxyurea plus aspirin gave fewer arterial clots, less bleeding and less progression to myelofibrosis than anagrelide plus aspirin.","refs":["pt-1","hydroxyurea","anagrelide"]},{"year":2013,"title":"CALR mutations discovered","note":"Klampfl and Nangalia find CALR exon 9 mutations in most JAK2-negative ET and myelofibrosis.","refs":[]},{"year":2016,"title":"WHO separates prefibrotic myelofibrosis from ET","note":"Marrow histology now distinguishes true ET from early myelofibrosis, which carries a worse outlook.","refs":[]},{"year":2017,"title":"MAJIC-ET: ruxolitinib not superior","note":"Ruxolitinib matched but did not beat best available therapy after hydroxyurea failure, though it eased symptoms.","refs":["majic-et","ruxolitinib"]},{"year":2023,"title":"Bomedemstat enters phase 3","note":"Merck starts the Shorespan-007 trial against hydroxyurea in high-risk ET.","refs":["bomedemstat"]}],"pipeline":["bomedemstat","ropeginterferon-alfa-2b"],"openProblems":["No treatment has been shown to prevent progression to myelofibrosis or leukaemia.","Very low-risk patients receive nothing and low-risk patients aspirin, but the evidence for aspirin in CALR-mutated low-risk disease is thin and bleeding may outweigh benefit.","Prefibrotic myelofibrosis is still often misdiagnosed as ET, and the two need different counselling.","Pregnancy management rests on small series; interferon is preferred but randomised data are lacking."]},"route":"/cancers/essential-thrombocythaemia/","neighbours":{"cancer":[{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"}],"term":[{"id":"erythromelalgia","kind":"term","name":"Erythromelalgia","route":"/terms/erythromelalgia/"},{"id":"jak2-v617f","kind":"term","name":"JAK2 V617F","route":"/terms/jak2-v617f/"},{"id":"post-pv-myelofibrosis","kind":"term","name":"Post-PV myelofibrosis (spent phase)","route":"/terms/post-pv-myelofibrosis/"}],"trial":[{"id":"majic-et","kind":"trial","name":"MAJIC-ET","route":"/trials/majic-et/"},{"id":"pt-1","kind":"trial","name":"PT-1 (Primary Thrombocythaemia 1)","route":"/trials/pt-1/"}],"drug":[{"id":"anagrelide","kind":"drug","name":"Anagrelide","route":"/drugs/anagrelide/"},{"id":"aspirin","kind":"drug","name":"Aspirin","route":"/drugs/aspirin/"},{"id":"bomedemstat","kind":"drug","name":"Bomedemstat","route":"/drugs/bomedemstat/"},{"id":"hydroxyurea","kind":"drug","name":"Hydroxyurea (hydroxycarbamide)","route":"/drugs/hydroxyurea/"},{"id":"peginterferon-alfa-2b","kind":"drug","name":"Peginterferon alfa-2b","route":"/drugs/peginterferon-alfa-2b/"},{"id":"ropeginterferon-alfa-2b","kind":"drug","name":"Ropeginterferon alfa-2b","route":"/drugs/ropeginterferon-alfa-2b/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"target":[{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"}]}}