Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by sustained thrombocytosis (platelet count >=450,000/microL) due to clonal proliferation of bone marrow megakaryocytes. Annual incidence is 1-2.5 per 100,000 with median age 60 years and bimodal distribution (smaller peak in young women aged 30 years). Driver mutations: JAK2 V617F (~60%), CALR exon 9 (~25%, type 1 with 52-bp deletion or type 2 with 5-bp insertion), MPL exon 10 (~3%, W515 mutations); approximately 10% are triple-negative.
WHO 2022 diagnostic criteria require all 4 major OR first 3 major + minor: Major: (1) Platelet count >=450,000/microL; (2) Bone marrow biopsy showing predominantly megakaryocyte lineage proliferation with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei (no significant left shift in granulopoiesis or erythropoiesis, minimal or no fibrosis); (3) Not meeting WHO criteria for BCR::ABL1+ CML, PV, primary myelofibrosis, MDS, or other myeloid neoplasm; (4) Presence of JAK2, CALR, or MPL mutation. Minor: presence of clonal marker (other mutation) or absence of evidence for reactive thrombocytosis. Differential diagnosis includes reactive thrombocytosis (iron deficiency, infection, inflammation, splenectomy, malignancy), other MPNs (PV, primary myelofibrosis), and chronic myeloid leukemia.
Risk stratification uses IPSET-thrombosis: age >60 years (1 point), JAK2 V617F mutation (2 points), cardiovascular risk factors (1 point), prior thrombosis (1 point); 0-1 = low risk, 2 = intermediate, >=3 = high risk. Treatment: very low risk (age <60, no JAK2 mutation, no prior thrombosis) may be observed; low risk (JAK2+ alone) receives low-dose aspirin; intermediate risk receives aspirin +/- cytoreduction; high risk requires cytoreduction plus aspirin. First-line cytoreductive options include hydroxyurea 500-2000 mg daily, anagrelide 1-3 mg daily (specific for platelets, may worsen anemia and cause cardiovascular effects), pegylated interferon alfa-2a or ropeginterferon (preferred for younger patients and pregnancy, may achieve molecular remission). Ruxolitinib studied for hydroxyurea-resistant ET. Major complications include arterial and venous thrombosis (cardiovascular events, stroke, splanchnic vein thrombosis), bleeding (especially with platelets >1,500,000/microL from acquired von Willebrand syndrome), pregnancy complications (recurrent miscarriage, preeclampsia, placental insufficiency), transformation to post-ET myelofibrosis (4-9% at 15 years) and acute leukemia (1-5% at 20 years).