Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Department of Cardiometabolic Research, Boehringer Ingelheim, Biberach, Germany.
Ann Neurol. 2015 Jul;78(1):137-41. doi: 10.1002/ana.24421.
Lack of specific antidotes is a major concern in intracerebral hemorrhage (ICH) related to direct anticoagulants including dabigatran (OAC-ICH). We examined the efficacy of idarucizumab, an antibody fragment binding to dabigatran, in a mouse model of OAC-ICH. Dabigatran etexilate (DE) dose-dependently prolonged diluted thrombin time and tail-vein bleeding time, which were reversed by idarucizumab. Pretreatment with DE increased intracerebral hematoma volume and cerebral hemoglobin content. Idarucizumab in equimolar dose prevented excess hematoma expansion for both DE doses. In more extensive ICH, idarucizumab significantly reduced mortality. Thus, idarucizumab prevents excess intracerebral hematoma formation in mice anticoagulated with dabigatran and reduces mortality.
缺乏特异性解毒剂是与直接抗凝剂相关的脑出血(ICH)的主要关注点,包括达比加群(OAC-ICH)。我们在一种使用达比加群的 OAC-ICH 小鼠模型中检验了idarucizumab(一种与达比加群结合的抗体片段)的疗效。依达赛珠单抗可剂量依赖性地延长稀释凝血酶时间和尾静脉出血时间,而idarucizumab 可逆转这一作用。达比加群酯预处理可增加脑内血肿体积和脑内血红蛋白含量。idarucizumab 以等摩尔剂量预防了两种达比加群剂量的过度血肿扩大。在更广泛的 ICH 中,idarucizumab 显著降低了死亡率。因此,idarucizumab 可防止达比加群抗凝的小鼠发生过度脑内血肿形成,并降低死亡率。