Anticoagulation therapy is indicated for management of various clinical 
conditions to prevent adverse events and introduction of direct oral 
anticoagulants (DOACs) has ushered in a new era in anticoagulation therapy. 
Major advantages of DOACS include fewer drug interactions and that they do not 
need periodic monitoring. Several patients who were not on anticoagulation 
before due to older age, polypharmacy/drug interaction concerns, and logistics 
of periodic monitoring are now on anticoagulation with DOACs. Despite their many 
advantages, a challenge while prescribing DOACs is very limited availability of 
specific reversal agents and lack of understanding or guidance about the 
treatment strategy in case of major life threatening bleeding or need for urgent 
surgery. So far only one reversal agent has been approved by the Food and Drug 
Administration (FDA), idarucizumab for one of the DOACs i.e., dabigatran. 
Several other reversal agents are under final phases of development such as 
andexanet alfa and PER977 (ciraparantag) and will help in developing specific 
strategies for reversal of these agents. In this article, we review current 
strategies to manage bleeding with DOACs and provide guidance to clinicians of 
inhibiting LF activity in vitro and in cells, as well as in animal models of 
anthrax infection.