Mortality following major gastrointestinal bleeding among patients receiving direct oral anticoagulants

Direct oral anticoagulants (DOACs) are increasingly used for the treatment of cancer-associated venous thromboembolism (CAT). However, concerns remain regarding bleeding complications, particularly gastrointestinal (GI) bleeding, and their associated morbidity and mortality in patients with cancer. This narrative review summarizes available evidence on the epidemiology, predictors, mortality, and management of DOAC-associated major GI bleeding in this high-risk population. Across randomized controlled trials, major bleeding rates with DOACs range from 4 to 7%, with GI bleeding accounting for much of the observed excess bleeding, compared with low molecular weight heparin (LMWH), particularly among patients with unresected upper GI cancers. Observational studies in the cancer population confirm that GI bleeding is the predominant site of major bleeding complications, and it is associated with substantial 30-day mortality rates of 10-20%. Evidence to guide anticoagulation resumption after GI bleeding in patients with cancer is limited. Available data suggest that resumption of anticoagulation reduces thromboembolic events and all-cause mortality at the cost of increased recurrent bleeding risk, with early resumption associated with the highest rates of rebleeding events. In conclusion, GI bleeding is a frequent and clinically important complication of DOAC therapy in patients with cancer, highlighting the importance of individualized, multidisciplinary, and patient-centered management strategies.