When idarucizumab was added to ex vivo blood samples, the coagulation parameters were corrected, as demonstrated by the restoration of PT, aPTT, CT, and CFT to baseline levels. Keywordsĭabigatran etexilate (oral 30 mg twice daily for 3 days followed by intravenous infusion of 0.77 mg/kg/h for 30 minutes and 0.52 mg/kg/h for 60 minutes) was administered to the animals before injury to achieve consistent supratherapeutic plasma concentrations as demonstrated by prolonged prothrombin time (PT), aPTT, CT, and CFT. These findings provide initial evidence that idarucizumab could provide a safe and effective means of reversing anticoagulant activity in patients treated with dabigatran in need of emergency surgery or in emergency bleeding situations. In the absence of dabigatran, idarucizumab showed no effect on coagulation parameters or thrombin formation. In the phase 1 trials, at doses of 2 g or greater, idarucizumab resulted in immediate and complete reversal of the dabigatran anticoagulant effects and was well tolerated. The reversal of the anticoagulant effects of dabigatran by idarucizumab has been demonstrated in animal bleeding models, in healthy volunteers with a range of ages and renal function, and in anticoagulated patients. Idarucizumab is a humanized monoclonal antibody fragment that binds with high affinity to free and thrombin-bound dabigatran, resulting in an almost irreversibly bound idarucizumab–dabigatran complex and thereby neutralizing dabigatran's anticoagulant activity. Food and Drug Administration and the European Medicines Agency for use in patients treated with dabigatran when urgent reversal of its anticoagulant effects is needed. This includes the specific reversal agent idarucizumab, which has been approved by the U.S. Therefore, several reversal agents for the DOACs are in development. However, as with all anticoagulants, bleeding complications may occur, and anticoagulant reversal may be required in specific clinical situations, such as in patients experiencing spontaneous or traumatic bleeds, or in anticoagulated patients requiring emergency surgery or other invasive procedures. The direct oral anticoagulants (DOACs) provide a number of clinical advantages over vitamin K antagonists for the treatment of thromboembolism, including improved efficacy and safety, as well as no need for regular monitoring of anticoagulant effect.
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