Department of Emergency Medicine, Wexner Medical Center, The Ohio State University, Columbus, Ohio.
Anticoagulation Services, Sanford University of South Dakota Medical Center, Sioux Falls, South Dakota.
J Emerg Med. 2020 Feb;58(2):217-233. doi: 10.1016/j.jemermed.2019.10.011. Epub 2019 Dec 10.
The management of life-threatening bleeding in patients who are receiving direct oral anticoagulants (DOACs) is a serious medical concern.
This review provides a concise, balanced overview of the current and future approaches for reversing the anticoagulation effects of DOACs, particularly factor Xa (FXa) inhibitors.
The anticoagulant activity of the direct thrombin inhibitor dabigatran can be reversed by idarucizumab, but until recently, options for the management of major bleeding in patients who were receiving FXa inhibitors were limited to nonspecific strategies, including supplementation of clotting factors with prothrombin complex concentrates (PCCs) or activated PCCs for attenuating anticoagulation effects. They appear as a treatment option in many hospital guidelines despite the lack of approval by the U.S. Food and Drug Administration and the lack of rigorous medical evidence supporting their use in this setting. The development of specific reversal agents may provide improved strategies for the management of bleeding. Andexanet alfa is a modified FXa molecule approved in the United States to reverse the anticoagulant effects of FXa inhibitors (rivaroxaban and apixaban) in patients with life-threatening or uncontrolled bleeding. Ciraparantag is a small-molecule inhibitor of multiple anticoagulants that has been investigated in healthy subjects.
The current guidelines for management of DOAC-associated bleeding are being updated to reflect that the reversal agent for rivaroxaban and apixaban is now available. For other FXa inhibitors, in the absence of a reversal agent, nonspecific strategies that include PCCs are recommended. The population of patients anticoagulated with DOACs is growing, and we hope that specific reversal agents will improve the approach to management of major bleeding in this population.
接受直接口服抗凝剂（DOAC）治疗的患者发生危及生命的出血时，需要进行紧急处理，这是一个严峻的医学问题。
本文简要、平衡地概述了逆转 DOAC 抗凝作用的当前和未来策略，特别是针对 Xa 因子（FXa）抑制剂。
直接凝血酶抑制剂达比加群的抗凝活性可被依达鲁单抗逆转，但直到最近，接受 FXa 抑制剂治疗的患者发生大出血时的处理方法仍非常有限，主要是非特异性策略，包括使用凝血酶原复合物浓缩物（PCC）或活化的 PCC 来补充凝血因子，以减弱抗凝作用。尽管这些方法尚未获得美国食品药品监督管理局（FDA）的批准，也缺乏在这种情况下使用这些方法的严格医学证据，但它们在许多医院指南中被视为治疗选择。特异性逆转剂的开发可能为出血的处理提供更优策略。Andexanet alfa 是一种修饰的 FXa 分子，在美国被批准用于逆转危及生命或不受控制的出血患者的 FXa 抑制剂（利伐沙班和阿哌沙班）的抗凝作用。Ciraparantag 是一种多抗凝剂的小分子抑制剂，已在健康受试者中进行了研究。
目前 DOAC 相关出血处理的指南正在更新，以反映利伐沙班和阿哌沙班的逆转剂现已上市。对于其他 FXa 抑制剂，在没有逆转剂的情况下，建议使用包括 PCC 在内的非特异性策略。接受 DOAC 抗凝治疗的患者人数不断增加，我们希望特异性逆转剂将改善此类患者大出血的处理方法。
