Stellpflug Samuel J, Bond Michael E, Henry Keith D, Engebretsen Kristin M, Zantek Nicole D
Department of Emergency Medicine, Regions Hospital, 640 Jackson Street, Saint Paul, MN 55101 USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN USA.
Indian J Hematol Blood Transfus. 2021 Jan;37(1):101-107. doi: 10.1007/s12288-020-01309-5. Epub 2020 Jun 22.
Dabigatran etexilate is an oral direct thrombin (Factor IIa) inhibitor approved for patients with atrial fibrillation and for management of risk of deep vein thrombosis and pulmonary embolism. Dabigatran offers advantages over treatment with warfarin, including limited laboratory monitoring. It is equivalent in prevention of stroke and deep vein thrombosis with essentially equivalent complication rates. In contrast to warfarin, reversal of the anticoagulation is less well established. Idarucizumab is available for reversal, however supporting research is mixed; the agent also happens to be quite expensive making availability difficult. Hemodialysis has been proposed as a method of reversal, but this is difficult in patients with life threatening hemorrhage, and is not available at many hospitals. Intravenous fat emulsion (IFE) has been used for treatment of overdose of lipophilic drugs. Most toxicologists only recommend IFE for patients in extremis after ingestion of a lipid soluble substance. Dabigatran is lipid soluble, although the pro-drug more so than the active metabolite. The authors sought to see if dabigatran-induced coagulopathy of human in vitro blood samples could be reversed with IFE. Blood samples were spiked with dabigatran or dabigatran plus IFE. Values for Ecarin clot time (ECT-primary outcome), PT/INR, and aPTT, were compared across both study arms. A total of 18 healthy volunteers were included in our study. There were no significant differences in the ECT, PT/INR, and aPTT between the dabigatran arm and the dabigatran plus IFE arm. Based on these methods, IFE does not reverse dabigatran-induced coagulopathy.
达比加群酯是一种口服直接凝血酶(因子IIa)抑制剂,已被批准用于房颤患者以及治疗深静脉血栓形成和肺栓塞的风险。与华法林治疗相比,达比加群具有优势,包括所需的实验室监测较少。在预防中风和深静脉血栓形成方面,它与华法林相当,并发症发生率基本相同。与华法林不同的是,其抗凝作用的逆转方法尚未完全确立。艾达凝血酶原复合物可用于逆转抗凝作用,然而支持性研究结果不一;而且该药物价格昂贵,难以广泛使用。血液透析已被提议作为一种逆转方法,但对于有危及生命的出血的患者来说,这很困难,而且许多医院都没有这种设备。静脉注射脂肪乳剂(IFE)已被用于治疗亲脂性药物过量。大多数毒理学家仅建议在摄入脂溶性物质后处于极端情况的患者使用IFE。达比加群是脂溶性的,尽管前体药物比活性代谢物的脂溶性更强。作者试图研究IFE是否能逆转达比加群在人体体外血样中引起的凝血障碍。血样中加入了达比加群或达比加群加IFE。比较了两个研究组的蝰蛇毒凝血时间(ECT-主要结果)、PT/INR和活化部分凝血活酶时间(aPTT)值。我们的研究共纳入了18名健康志愿者。达比加群组和达比加群加IFE组之间的ECT、PT/INR和aPTT没有显著差异。基于这些方法,IFE不能逆转达比加群引起的凝血障碍。