Gressenberger Paul
Division of Angiology, Department of Internal Medicine, Medical University of Graz, Austria.
Vasa. 2019 Aug;48(5):389-392. doi: 10.1024/0301-1526/a000777. Epub 2019 Feb 5.
Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF. Since DOACs have very short plasma elimination half-lives compared to VKA, for most bleeding events, expert opinions suggest that withdrawal of DOACs and supportive care will likely suffice to stop a bleeding episode. Because there is a bleeding risk associated with DOACs, reversal strategies may be needed if a patient receiving DOAC therapy bleeds during surgery or an invasive procedure. So far, idarucizumab has been the only available antidote that binds specifically to dabigatran and safely and quickly reverses its anticoagulant effects. Idarucizumab has no effects on anti Xa inhibitors or other anticoagulants. To date, treatment of serious, life-threatening bleeds in patients with anti-Xa-inhibitor has involved 4 factor prothrombin complex concentrates (PCC). PCC restores normal hemostasis laboratory values in most patients with major bleeding events after anti Xa inhibitor intake. Recently, the US Food and Drug Administration (FDA) approved andexanet alfa as the first specific antidote for the anti-Xa inhibitors apixaban and rivaroxaban. So far clinical experience with this substance and data comparing it with PCC are lacking. Currently ciraparantag is under investigation as a universal reversal agent for all DOACs and low molecular weight heparin as well. Because it is so broadly applicable, ciraparantag might be a good future option for the management of most bleeding complications under anticoagulant treatment. The aim of this review is to summarize recent study data and recommendations on nonspecific and specific DOAC reversal strategies and to present the current evidence.
目前，使用直接口服抗凝剂（DOACs）治疗静脉血栓形成事件（VTE）或非瓣膜性心房颤动（AF）已成为标准治疗方法，并且在众多临床研究中均显示出临床疗效和安全性。通常，这些药物的总体死亡率较低，脑出血风险较小，但根据药物种类和研究情况，与用于VTE和AF治疗的传统标准药物维生素K拮抗剂（VKA）相比，它们更易引起胃肠道出血。由于与VKA相比，DOACs的血浆消除半衰期非常短，因此对于大多数出血事件，专家意见认为停用DOACs并给予支持性治疗可能足以止血。由于DOACs存在出血风险，因此接受DOAC治疗的患者在手术或侵入性操作期间出血时可能需要逆转策略。到目前为止，艾达赛珠单抗是唯一可用的解毒剂，它能特异性结合达比加群，并安全、迅速地逆转其抗凝作用。艾达赛珠单抗对Xa因子抑制剂或其他抗凝剂无作用。迄今为止，抗Xa因子抑制剂治疗的患者发生严重、危及生命的出血时，治疗方法包括使用4因子凝血酶原复合物浓缩剂（PCC）。PCC可使大多数服用抗Xa因子抑制剂后发生大出血事件的患者恢复正常止血实验室值。最近，美国食品药品监督管理局（FDA）批准了andexanet alfa作为抗Xa因子抑制剂阿哌沙班和利伐沙班的首个特异性解毒剂。到目前为止，关于该药物的临床经验以及将其与PCC进行比较的数据均较为缺乏。目前，cirparantag正在作为所有DOACs以及低分子量肝素的通用逆转剂进行研究。由于其适用性广泛，cirparantag可能是未来处理抗凝治疗下大多数出血并发症的理想选择。本综述的目的是总结近期关于非特异性和特异性DOAC逆转策略的研究数据和建议，并展示当前证据。
