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逆转新型口服抗凝药的抗凝作用:环帕兰特、安多凝血素α及依达赛珠单抗的作用

Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab.

作者信息

Hu Tiffany Y, Vaidya Vaibhav R, Asirvatham Samuel J

机构信息

Mayo Medical School, Department of Internal Medicine, Rochester, MN, USA.

Division of Cardiovascular Diseases, Department of Internal Medicine, Rochester, MN, USA.

出版信息

Vasc Health Risk Manag. 2016 Feb 17;12:35-44. doi: 10.2147/VHRM.S89130. eCollection 2016.

Abstract

Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.

摘要

新型口服抗凝药(NOACs)在临床实践中的应用日益广泛,但缺乏可商购的逆转剂是这些疗法广泛应用的主要障碍。针对NOACs的特异性解毒剂正在研发中。依达赛珠单抗(aDabi-Fab,BI 655075)是一种新型人源化小鼠单克隆抗体,可结合达比加群并逆转其抗凝作用。在最近的一项III期研究(依达赛珠单抗对活性达比加群的逆转作用)中,静脉输注5 g依达赛珠单抗后,在两组研究对象中,稀释凝血酶时间正常化的比例分别为98%和93%,蛇静脉酶凝结时间正常化的患者比例分别为89%和88%。另外两种解毒剂,andexanet alfa(PRT064445)和ciraparantag(PER977)也在研发中,用于逆转NOACs的作用。在本综述中,我们讨论了使用NOACs时常见的管理问题,如围手术期管理、抗凝的实验室监测以及出血的处理。我们回顾了目前关于NOACs特异性解毒剂在药理学和临床试验方面的现有数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/4762436/40ff0f81942b/vhrm-12-035Fig1.jpg

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