The vitamin K antagonists (VKAs) have been the standard (and only) oral 
anticoagulants used for the long-term treatment or prevention of venous 
thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy 
induced by VKAs can be reversed with vitamin K, and in urgent situations, the 
vitamin K-dependent coagulation factors can be replaced by transfusion. In the 
last decade, a new class of oral anticoagulants has been developed, direct oral 
anticoagulants that bind to a specific coagulation factor and neutralize it. 
These compounds were shown to be effective and safe compared with the VKAs and 
were licensed for specific indications, but without a specific reversal agent. 
The absence of a reversal agent is a barrier to more widespread use of these 
agents. Currently, for the management of major life-threatening bleeding with 
the direct oral anticoagulants, most authorities recommend the use of four 
factor prothrombin complex concentrates. There are now three reversal agents in 
development and poised to enter the market. Idarucizumab is a specific antidote 
targeted to reverse the direct thrombin inhibitor, dabigatran, which was 
recently approved for use in the USA. Andexanet alfa is an antidote targeted to 
reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor 
enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin 
and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.