Pb2191: a retrospective multi-center study on direct oral anticoagulant use in bcr::abl1 negative myeloproliferative neoplasms

Topic: 16. Myeloproliferative neoplasms - Clinical Background: The risk of thrombotic events is high in patients with BCR::ABL1 negative myeloproliferative neoplasms (MPNs). Venous thromboembolism (VTE), arterial thrombosis, particularly atypical site VTE, are the leading causes of morbidity and mortality in patients with MPNs, despite the substantial advancements in our understanding of the pathophysiology, risk stratification, and successful biologic therapies. In general population direct oral anticoagulants (DOACs) have become the preferred treatment for secondary VTE prevention and thrombosis prophylaxis in nonvalvular atrial fibrillation (NVAF). However, there is still limited evidence on their efficacy and safety of DOACs in MPN, which is mainly based on retrospective observational studies Aims: In this multi-center retrospective study, we assessed the risk of thrombosis and bleeding in a group of BCR::ABL1 negative MPN patients receiving DOACs. The goal of this study was to describe DOAC use in MPNs in a real-world scenario, including usage patterns and thrombosis/bleeding outcomes. Methods: MPN patients receiving DOAC for thrombosis or NVAF between 2014 and 2022 in thirteen medical centers in Turkey were included. We gathered information about demographic clinical data of the patients. The DOACs were started as first-line anticoagulant therapy or after a prior course of vitamin K antagonist (VKA) therapy, and the dosage was given in accordance with VTE and NVAF recommendations, with adjustments made for body weight or liver and kidney function. We assessed the efficacy and safety of DOACs. Regarding safety, we documented the bleeding episodes classified as major, minor, and clinically relevant non-major (CRNM) by the International Society of Thrombosis and Hemostasis (ISTH). Results: Of the 45 patients included in our analysis 25 (55.6%) were female. Twenty-one patients (46.7%) had essential thrombocythemia (ET), 20 (44.4%) and four (8.8%) patients had polycythemia vera (PV) and myelofibrosis (MF), respectively. Thirty-seven patients (82.2%) harbored JAK2V617F mutation, one patient (2.2 %) had CALR mutation, and 7 (15.6%) were triple negative. Thirty-nine patients (86.7%) were using hydroxyurea for cytoreduction, 4 patients (8.9 %) were on pegylated interferon alpha, and one patient (2.2%) each were receiving ruxolitinib and anagrelide. Median duration of DOAC use was 33.5 months. Reason for DOAC initiation was NVAF in 11 patients (24.4%), thrombosis in 20 patients (44.4 %), NVAF and thrombosis in 14 (31.1%). Thirty-two patients (71.1%) switched to DOAC from a prior anticoagulant [25 patients from VKA and 7 from low molecular weight heparin (LMWH)], and 13 patients (28.9%) received upfront DOAC therapy. Reasons for switching to DOAC therapy include failure to reach therapeutic INR levels and/or recurrence of thrombosis under VKA, and difficulties in using LMWH. Thirteen (38.2 %), 15 (44.1 %), and 6 patients (17.7%) had thrombosis prior to, at the time of, and after the diagnosis of MPN, respectively. Twenty-two patients (48.9%) are on rivaroxaban, 16 (35.6 %) are receiving apixaban, and 4 (8.9 %) and three (6.7%) patients are on edoxaban and dabigatran, respectively. A total of seven bleeding events were recorded. Heavy menstrual and clinically relevant non-major bleedings occurred in 5 (71.4%) and two (28.6%) patients, respectively. Recurrent thrombosis occurred in four patients (8.8%), including 3 arterial thrombosis and one deep venous thrombosis. Summary/Conclusion: Real-world data on the use of DOAC in patients with MPN from this multi-center experience indicate that DOACs are safe in MPN. Our data enhance the case for pursuing future prospective lines of research that assess DOACs for thromboprophylaxis in MPN patients.Keywords: Oral anticoagulant, Anticoagulation, Myeloproliferative disorder, Anticoagulants