JAK2 V617F induces biological changes to megakaryocytes and platelets leading to increased thrombotic events. The presence of JAK2 V617F leads to (1) hypersensitive signaling through the thrombopoietin (TPO)/MPL pathway in megakaryocytes, leading to increased activation of downstream molecules such as signal transducer and activator of transcription 3 and extracellular signal-regulated kinase. Phenotypically, this manifests in (2) increased ploidy and mobility of JAK2 V617F megakaryocytes; (3) increased formation of proplatelets; and (4) increased aggregation, spreading, and thrombus formation of platelets. The ultimate consequence of these biological changes is (5) decreased bleeding volumes in response to injury and increased thrombotic events.