Pathophysiology
Clinical meaning
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by clonal megakaryocyte proliferation in the bone marrow, resulting in sustained platelet elevation (>450,000/mcL). Three driver mutations account for ~90% of ET cases: (1) JAK2 V617F mutation (~60%): causes constitutive activation of the JAK-STAT signaling pathway, driving megakaryocyte proliferation independent of thrombopoietin (TPO) stimulation; (2) CALR (calreticulin) mutation (~25%): activates the MPL (thrombopoietin receptor) pathway through an alternative mechanism; (3) MPL mutation (~5%): directly activates the thrombopoietin receptor. The remaining ~10% are 'triple-negative' (no detectable driver mutation). ET has a paradoxical dual risk: THROMBOTIC complications (stroke, TIA, MI, DVT, PE, digital ischemia, erythromelalgia, portal/splenic vein thrombosis) from excessive platelet activation and aggregation, AND HEMORRHAGIC complications (especially at very high platelet counts >1,000,000/mcL) from acquired von Willebrand disease (excessive platelets absorb and degrade large VWF multimers, impairing primary hemostasis). Risk stratification guides therapy: the IPSET-thrombosis score classifies patients as very low, low, intermediate, or high risk based on age (โฅ60), JAK2 mutation status, and history of thrombosis. The nurse monitors CBC with platelet count trends, assesses for thrombotic symptoms (headache, visual changes,...