Non-vitamin K oral anticoagulants (NOACs) have been a major addition to our 
therapeutic armamentarium. They are at least as effective as warfarin in the 
thromboprophylaxis of non-valvular atrial fibrillation and management of 
thromboembolic disease, with a more favorable safety profile. Their predictable 
pharmacokinetics and pharmacodynamics allow for a fixed oral dosing without the 
need for anticoagulation monitoring. A major concern regarding NOACs is the lack 
of a readily available antidote to reverse their anticoagulation effect in case 
of life-threatening bleeding or need for emergent surgery. In this review, we 
summarize preclinical and clinical data on (a) hemostatic agents used to reverse 
NOACs, and (b) novel, target-specific NOACs reversal agents under development. 
The prothrombin complex concentrates, activated prothrombin complex concentrates 
and recombinant activated factor VII are hemostatic agents that have been 
assessed in reversing NOACs. Preclinical studies with hemostatic agents report 
variable results and there is only limited clinical data available to date. 
Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to 
reverse dabigatran and factor Xa inhibitors accordingly. Aripazine is a 
universal anticoagulation reversal agent. Preclinical studies show promising 
results and these agents are already in different stages of clinical 
development. Phase I and II clinical trials demonstrate efficacy in reversing 
NOACs without major side effects. Until these agents become commercially 
available, management of patients receiving NOACs who present with major 
bleeding or require emergent surgery should focus on (a) immediate 
discontinuation of NOACs, (b) supportive measures or postponing surgery for 
12-24 h after the last NOAC dose, and/or