The direct oral anticoagulants (DOACs) have gained popularity recently among 
both patients and providers for their comparable or better efficacy and safety 
profiles compared with warfarin and the lack of need for routine monitoring of 
anticoagulant effect. One obstacle for the more widespread use of the DOACs in 
clinical practice has been the lack of a reversal agent. Most DOACs act by 
directly binding to and inhibiting the effects of factor Xa. Andexanet alfa 
(Andexxa, Portola Pharmaceuticals, San Francisco, CA) is a modified form of 
factor Xa that acts as a decoy binding entity for DOACs, thereby allowing 
endogenous factor Xa to perform its normal clotting functions. Andexanet has 
proven efficacious in clinical trials for reversing the anticoagulant effects of 
apixaban, edoxaban, and rivaroxaban, although its impact on clinical outcomes 
has not been adequately studied. Andexanet has a boxed warning for 
thromboembolic risks, ischemic risks, cardiac arrest, and sudden death, with 
these adverse events occurring in up to 18% of patients in clinical trials. 
However, the occurrence of these adverse events needs to be considered in 
relation to the fragile nature of patients who receive this agent. Because the 
duration of the DOACs is much less than that of warfarin, it is unclear how many 
patients would actually need andexanet in clinical practice, because cessation 
of the DOAC may be all that is needed to effectively manage bleeding. 
Nonetheless, having andexanet available in cases of DOAC-associated severe or 
life-threatening bleeding represents a therapeutic advance and should provide an 
added level of comfort with the clinical use of DOACs.