Thrombosis, major bleeding, and mortality in 1 079 myelofibrosis patients, a matched population-based study

• This nationwide study shows that major bleeding and thromboembolic events are more frequent in MF than previously described in other MPN.

• Use of JAK inhibitors or LMWH, a previous thrombosis and higher age were associated with an increased risk of a new thromboembolic event.

Bleeding and thrombotic events are known complications in myeloproliferative neoplasms (MPN), but few studies are exclusively focusing on patients with myelofibrosis (MF). In this nationwide population-based study, we assessed the frequency of major bleeding, thrombotic events and all cause-mortality in 1 079 patients diagnosed with MF and 5 395 matched controls, using multiple Swedish Health Care Registers. Major bleeding, arterial and venous events were seen at a rate of 2.55, 2.59 and 1.06 events per 100 years in patients with MF. Compared to controls, the rates of bleedings, arterial events, venous events and mortality were increased, HR 3.78 (95% CI 2.98-4.79, p<0.001), HR 1.73 (1.40-2.12, p<0.001), 2.75 (1.93-3.90, p<0.001) and HR 3.92 (3.50-4.40, p<0.001) respectively. Patients treated with JAK inhibitors (JAKi) had higher rates of major bleeding (5.33), arterial events (4.67) and venous events (1.56) than patients with no ongoing symptoms-directed therapy (rates 2.32, 2.15 and 0.79) or hydroxyurea (rates 2.05, 2.35 and 1.27). Use of JAKi, low-molecular-weight heparin (LMWH), previous arterial or venous event and higher age were identified as independent risk factors for a new arterial or venous event. A previous venous event, a higher leukocyte count at diagnosis and ongoing JAKi treatment were associated with an increased risk of major bleeding. Current study shows that patients with MF have higher rates of thromboembolic events and major bleeding than described in other MPN and thromboembolic complications and major bleeding diverges in the different treatment groups.