Pinto Ian, Giri Anshu, Arshad Umbreen, Gajra Ajeet
State University of New York, 750 E Adams Street, Syracuse, NY 13210, USA.
Curr Drug Saf. 2015;10(3):208-16. doi: 10.2174/1574886310666150416123530.
The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation.
新型口服抗凝剂（NOAC）的出现增加了对抗血栓栓塞性疾病的手段，但也引发了关于其逆转的难题。NOAC与传统维生素K拮抗剂具有相当的疗效，严重出血发生率相似。然而，目前尚无这些药物逆转的标准化方法，也没有特效解毒剂。这不仅在急性出血事件中令人担忧，在需要急诊手术的临床情况下也令人担忧。最近的研究探讨了使用凝血酶原复合物浓缩物（PCC）、重组因子VIIa逆转达比加群、利伐沙班和阿哌沙班，对于达比加群还使用了单克隆抗体。这些研究令人鼓舞，表明在大多数模型中出血时间和失血量有所改善，尤其是使用PCC和达比加群抗体时。值得注意的是，目前大多数常用的凝血检测可能与临床逆转情况不相关。由于缺乏临床试验，NOAC导致的明显出血的管理很困难。目前的动物试验、病例报告以及对人体血液的止血检测已显示出一些希望；提供了指导，但仍需进一步研究。
