Risk of Bleeding in Essential Thrombocythemia Patients with Extreme Thrombocytosis.

About 25% of essential thrombocythemia (ET) patients present with extreme thrombocytosis (ExT), defined as having a platelet count ≥1000 x 10^9/L. ExT patients may have an increased bleeding risk associated with acquired von Willebrand syndrome. We retrospectively analyzed the risk of bleeding and thrombosis in ExT vs. non-ExT ET patients at Dana Farber Cancer Institute and Massachusetts General Hospital from 2014-2022 to inform treatment decisions. We abstracted the first major bleed, clinically relevant non-major bleed (CRNMB), and thrombotic event from medical records. We identified 128 (28%) ExT patients and 323 (72%) non-ExT patients. Cumulative incidence of bleeding was not different in ExT vs. non-ExT patients (21% vs. 13%, p=0.28 for major bleed; 16% vs. 15%, p=0.50 for CRNMB). Very low and low thrombotic risk ExT patients were more likely to be cytoreduced compared to very low and low risk non-ExT patients (69% vs. 50%, p=0.060 for very low risk; 83% vs. 53%, p=0.0059 for low risk). However, we found no differences in bleeding between ExT and non-ExT patients when restricting the risk of bleed from diagnosis to cytoreduction start date (28% vs. 19%, p=0.29 for major bleed; 24% vs. 22%, p=0.75 for CRNMB). Cumulative incidence of thrombosis was also not different between ExT and non-ExT patients (28% vs. 25%, p=0.98). This suggests that cytoreduction may not be necessary to reduce bleeding risk based only on a platelet count of 1 million. We identified novel risk factors for bleeding in ET patients including diabetes mellitus and the DNMT3A mutation.