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In addition, the presence of\n                      <jats:italic>JAK2<\/jats:italic>\n                      mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive\n                      <jats:italic>JAK2<\/jats:italic>\n                      ,\n                      <jats:italic>CALR<\/jats:italic>\n                      or\n                      <jats:italic>MPL<\/jats:italic>\n                      mutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Survival<\/jats:title>\n                    <jats:p>\n                      Median survivals are approximately 15\u2009years for PV and 18\u2009years for ET; the corresponding values for patients age 40 or younger were 37 and 35\u2009years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life\u2010expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET but risk of thrombosis is higher in\n                      <jats:italic>JAK2<\/jats:italic>\n                      mutated cases. Leukemic transformation rates at 10\u2009years are estimated at &lt;1% for ET and 3% for PV.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Thrombosis risk<\/jats:title>\n                    <jats:p>\n                      In PV, two risk categories are considered: high (age\u2009&gt;\u200960\u2009years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age\u2009\u2264\u200960\u2009years, no thrombosis history,\n                      <jats:italic>JAK2<\/jats:italic>\n                      wild\u2010type), low (same as very low but\n                      <jats:italic>JAK2<\/jats:italic>\n                      mutation present), intermediate (age\u2009&gt;\u200960\u2009years, no thrombosis history,\n                      <jats:italic>JAK2<\/jats:italic>\n                      wild\u2010type) and high (thrombosis history present\n                      <jats:styled-content>or<\/jats:styled-content>\n                      age\u2009&gt;\u200960\u2009years with\n                      <jats:italic>JAK2<\/jats:italic>\n                      mutation).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Risk\u2010adapted therapy<\/jats:title>\n                    <jats:p>The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once\u2010daily or twice\u2010daily aspirin (81\u2009mg), in the absence of contraindications. Very low risk ET might not require therapy while aspirin therapy is advised for low risk disease. Cytoreductive therapy is recommended for high\u2010risk ET and PV, but it is not mandatory for intermediate\u2010risk ET. First\u2010line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second\u2010line drugs of choice are interferon\u2010\u03b1 and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>New treatment directions<\/jats:title>\n                    <jats:p>Controlled studies are needed to confirm the clinical outcome value of twice\u2010daily vs once\u2010daily aspirin dosing and the therapeutic role of pegylated interferons and direct oral anticoagulants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.26008","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T01:58:05Z","timestamp":1600999085000},"page":"1599-1613","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":333,"title":["Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk\u2010stratification 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