Yates Scott W
P T. 2014 Dec;39(12):858-80.
Three target-specific oral anticoagulants (TSOACs)-dabigatran, rivaroxaban, and apixaban-have been approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; however, no agents are currently approved to reverse the anticoagulant effects of these TSOACs in cases of active bleeding. This review discusses the benefits and risks of these TSOACs from a clinician's perspective, with a focus on the interruption of treatment for either elective or emergent surgery, monitoring, and reversal of anticoagulation. Available coagulation assays are not ideal for monitoring the effects of TSOACs and do not provide reliable quantitative measurement of their anticoagulant effects. When necessary, activated partial thromboplastin time (aPTT) may provide qualitative information on dabigatran, and prothrombin time (PT) may provide qualitative assessment of the presence of the factor Xa inhibitors, rivaroxaban and apixaban. Current recommendations for reversal of TSOACs are based largely on limited and sometimes conflicting data from in vitro or in vivo animal models, and clinical experience with these recommendations is also limited. Methods that have been investigated for effectiveness for reversal of the pharmacodynamic effects of the TSOACs include dialysis, activated charcoal, prothrombin complex concentrate (PCC), and recombinant activated factor VII. It is important to note that even within a class of anticoagulant drugs, compounds respond differently to reversal agents; therefore, recommendations for one agent should not be extrapolated to another, even if they are from the same therapeutic class. New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors. Given the short half-lives of TSOACs, watchful waiting, rather than reversal, may be the best approach in some circumstances.
三种靶向特异性口服抗凝剂（TSOACs）——达比加群、利伐沙班和阿哌沙班——已获美国食品药品监督管理局（FDA）批准，用于降低非瓣膜性心房颤动患者中风和全身性栓塞的风险；然而，目前尚无药物被批准用于在发生活动性出血时逆转这些TSOACs的抗凝作用。本综述从临床医生的角度讨论了这些TSOACs的益处和风险，重点关注择期或急诊手术时治疗的中断、监测以及抗凝作用的逆转。现有的凝血检测方法对于监测TSOACs的效果并不理想，无法提供其抗凝作用的可靠定量测量。必要时，活化部分凝血活酶时间（aPTT）可提供有关达比加群的定性信息，而凝血酶原时间（PT）可对Xa因子抑制剂利伐沙班和阿哌沙班的存在进行定性评估。目前关于逆转TSOACs的建议很大程度上基于体外或体内动物模型的有限且有时相互矛盾的数据，并且这些建议的临床经验也很有限。已研究的用于逆转TSOACs药效学作用的方法包括透析、活性炭、凝血酶原复合物浓缩物（PCC）和重组活化因子VII。需要注意的是，即使在一类抗凝药物中，不同化合物对逆转剂的反应也不同；因此，一种药物的建议不能外推至另一种药物，即使它们属于同一治疗类别。正在探索新的解毒剂，包括达比加群的小鼠单克隆抗体；andexanet alfa，一种潜在的通用Xa因子抑制剂逆转剂；以及一种可能对Xa因子抑制剂和直接凝血酶抑制剂逆转有效的合成小分子（PER977）。鉴于TSOACs的半衰期较短，在某些情况下，密切观察而非逆转可能是最佳方法。
