> A Rapid Pro-Hemostatic Approach to Overcome Direct Oral Anticoagulants > > Thalji et al > > Nat Med . 2016;22:924–932. Direct oral anticoagulants have revolutionized long-term anticoagulant therapy because they are at least as effective, but safer and easier to administer than vitamin K antagonists. Nonetheless, when life-threatening bleeding occurs, reversal of the direct oral anticoagulants is necessary. A prohemostatic factor Xa variant was developed to address this unmet need. The direct oral anticoagulants (DOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, can be given in fixed doses without routine coagulation monitoring. In clinical trials, the DOACs have been shown to be at least as effective as vitamin K antagonists (VKAs), such as warfarin, for stroke prevention in nonvalvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less serious bleeding. With similar efficacy, better safety, and greater convenience, the DOACs are now replacing VKAs for these indications. Although the risk of serious bleeding, particularly intracranial bleeding, is reduced with the DOACs, drug reversal is needed when major bleeding occurs or if patients require urgent surgery. Idarucizumab is widely available for dabigatran reversal, but there are no licensed reversal agents for rivaroxaban, apixaban, or edoxaban. FXaI16L is a recombinant factor (F) Xa variant with a novel mechanism of action. A prohemostatic agent, FXaI16L, shows promise for controlling bleeding not only with the DOACs, but also in hemophilia patients with inhibitors. Thrombosis is the underlying cause of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, and most heart attacks and strokes. On a global basis, thrombosis accounts for 1 of 4 deaths, and this number is likely to rise with the aging population.1 With this burden of disease, it is not surprising that more and more patients are on long-term anticoagulant therapy for the prevention or treatment …