Direct oral anticoagulant failure in patients with venous thromboembolism-why and what next?

Management of recurrent thrombotic events in patients taking a direct oral anticoagulant can be challenging. In this review, we consider causes of so-called direct oral anticoagulant failure, from poor adherence, malabsorption, and drug interactions to the presence of undiagnosed antiphospholipid syndrome, cancer-associated thrombosis, severe thrombophilia, vasculitis, and other rare causes. We discuss the known or potential pathogenesis of venous thromboembolism recurrence in these situations and provide practical guidance to assist clinicians faced with these challenging cases.