Any bleed that requires hospitalization, surgical procedure, or transfusion likely requires interruption of the anticoagulant along with appropriate measures to control the source of bleeding.When a major bleed occurs, temporarily stopping the anticoagulant and initiating measures to control the bleeding source are required. A major bleed is one that involves a critical site, leads to hemodynamic instability, leads to a ≥2 g/dl hemoglobin decline, or requires ≥2 units of red blood cell transfusion.In this review, an overview of the current state of nonspecific and specific reversal agents for the direct factor Xa inhibitors is provided, focusing on the biochemistry and mechanism of action and the preclinical assessment of newly emerging therapies.The following are key points to remember from this American College of Cardiology (ACC) Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: Meanwhile, several specific reversal agents have been developed. In the absence of specific reversal agents, the off-label use of (activated) prothrombin complex concentrate and recombinant factor VIIa have been suggested as effective treatment options during inhibitor-induced bleeding complications. While idarucizumab has been established as an antidote for the direct thrombin inhibitor dabigatran, reversal strategies for the direct factor Xa inhibitors have been a focal point in clinical care over the past years. In case of bleeding or emergency surgery, reversal agents are helpful to counteract the anticoagulant therapy and restore hemostasis.

The direct oral anticoagulants targeting coagulation factor Xa or thrombin are widely used as alternatives to vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation.

Xa inhibitor reversal