BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) are 
approved for the prevention of stroke in patients with nonvalvular atrial 
fibrillation and for the treatment of venous thromboembolism. These include the 
direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors 
rivaroxaban, apixaban, and edoxaban. Bleeding is a complication for all 
anticoagulants and concerns regarding bleeding risk and the suitability of 
effective reversal strategies may be a barrier to their prescription. Despite 
the reduced risk of bleeding compared with vitamin K antagonists, questions 
persist regarding the management of bleeding related to NOAC use.
MAIN TEXT: To date, although a number of assays are responsive to NOACs, no 
single routine laboratory test has been identified to accurately measure the 
clinical anticoagulation state of patients on NOACs or established as a reliable 
predictor of bleeding risk. In addition, the establishment of a reliable human 
bleeding model to test novel inhibitors of the coagulation cascade has proved 
challenging. Although routine monitoring of anticoagulant levels is not 
necessary in patients taking NOACs, anticoagulant reversal and a means of 
measuring reversal may be required for patients who present with bleeding or 
require urgent surgery. Prothrombin complex concentrates are pooled plasma 
products containing varying amounts of inactive vitamin K-dependent clotting 
factors in addition to vitamin K-dependent proteins and can replenish factors in 
the intrinsic and extrinsic coagulation cascade, reversing an anticoagulant 
effect. Only one agent, idarucizumab, has been approved for rapid reversal of 
dabigatran-induced anticoagulation and one more agent, andexanet alfa, has been 
submitted for approval to reverse the anticoagulatory effects of direct and 
indirect factor Xa inhibitors.
CONCLUSIONS: This review discusses the laboratory tests available for assessing 
anticoagulation, human models of bleeding, and the use of current 
strategies-including prothrombin complex concentrates for reversal of 
anticoagulation by NOACs-to manage bleeding in patients.