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Bone marrow morphology typically shows increased number of mature\u2010appearing megakaryocytes distributed in loose clusters.<\/jats:p><jats:p><jats:bold><jats:italic>Genetics<\/jats:italic><\/jats:bold>: Approximately 80% of patients express myeloproliferative neoplasm driver mutations (<jats:italic>JAK2<\/jats:italic>, <jats:italic>CALR<\/jats:italic>, <jats:italic>MPL<\/jats:italic>), in a mutually exclusive manner; in addition, about 50% harbor other mutations, the most frequent being <jats:italic>TET2<\/jats:italic> (9%\u201311%), <jats:italic>ASXL1<\/jats:italic> (7%\u201320%), <jats:italic>DNMT3A<\/jats:italic> (7%), and <jats:italic>SF3B1<\/jats:italic> (5%). Abnormal karyotype is seen in &lt;10% of patients and includes +9\/20q\u2212\/13q\u2010.<\/jats:p><\/jats:sec><jats:sec><jats:title>Survival and Prognosis<\/jats:title><jats:p>Life expectancy is less than that of the control population. Median survival is approximately 18\u2009years but exceeds &gt;35\u2009years in younger patients. The triple A survival risk model, based on Age, Absolute neutrophil count, and Absolute lymphocyte count, effectively delineates high\u2010, intermediate\u20101\u2010, intermediate\u20102\u2010, and low\u2010risk disease with corresponding median survivals of 8, 14, 21, and 47\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Risk Factors for Thrombosis<\/jats:title><jats:p>Four risk categories are considered: very low (age \u226460\u2009years, no thrombosis history, <jats:italic>JAK2<\/jats:italic> wild\u2010type), low (same as very low but <jats:italic>JAK2<\/jats:italic> mutation present), intermediate (same as low but age &gt;60\u2009years), and high (thrombosis history or age &gt;60\u2009years with <jats:italic>JAK2<\/jats:italic> mutation).<\/jats:p><\/jats:sec><jats:sec><jats:title>Mutations and Prognosis<\/jats:title><jats:p><jats:italic>MPL<\/jats:italic> and <jats:italic>CALR\u20101<\/jats:italic> mutations have been associated with increased risk of MF transformation; spliceosome with inferior overall and MF\u2010free survival; <jats:italic>TP53<\/jats:italic> with leukemic transformation, and <jats:italic>JAK2<\/jats:italic>V617F with thrombosis. Leukemic transformation rate at 10\u2009years is &lt;1% but might be higher in <jats:italic>JAK2<\/jats:italic>\u2010mutated patients with extreme thrombocytosis and those with abnormal karyotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Treatment<\/jats:title><jats:p>The main goal of therapy is to prevent thrombosis. In this regard, once\u2010daily low\u2010dose aspirin is advised for all patients and twice daily for low\u2010risk disease. Cytoreductive therapy is advised for high\u2010risk and optional for intermediate\u2010risk disease. First\u2010line cytoreductive drugs of choice are hydroxyurea and pegylated interferon\u2010\u03b1 and second\u2010line busulfan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Additional Content<\/jats:title><jats:p>The current review includes specific treatment strategies in the context of extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post\u2010essential thrombocythemia MF, as well as new investigational drugs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajh.27216","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T09:55:20Z","timestamp":1706176520000},"page":"697-718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Essential thrombocythemia: 2024 update on diagnosis, risk stratification, and 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