Direct oral anticoagulants (DOACs, or non-vitamin K antagonist oral anticoagulants [NOACs]) include dabigatran, a direct thrombin inhibitor, and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban). They have largely replaced vitamin K anticoagulants (VKAs) in clinical practice. Their overall safety profile concerning bleeding appears to be at least equivalent, if not superior, to VKAs. However, the lack of a specific reversal agent for DOACs remains an important concern. Fortunately, there were recent remarkable innovations in management of DOAC-associated bleeding with the introduction of specific antidotes, including idarucizumab for dabigatran and andexanet alfa for factor Xa inhibitors. Still in development is ciraparantag, an agent purported to act as a “universal” reversal agent. In the following chapter, we will review the reversal strategies available for DOAC-treated patients who present with life-threatening bleeding or with indication for emergent surgery. We will also review the mechanism of action and data supporting the use of specific reversal agents, nonspecific pro-hemostatic therapies including prothrombin complex concentrate, and future research avenues.
