Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University Salzburg, Ignaz-Harrer-Str. 79, 5020, Salzburg, Austria.
Department of Neurology, King's College Hospital, Denmark Hill, London, UK.
CNS Drugs. 2017 Sep;31(9):747-757. doi: 10.1007/s40263-017-0460-x.
Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke.
We performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase.
We identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70-84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5-11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122-214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported.
Experience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.
目前的指南不建议在接受直接口服抗凝剂的急性缺血性脑卒中患者中使用静脉内重组组织型纤溶酶原激活剂。虽然人源化单克隆抗体依达鲁单抗可以迅速逆转凝血酶抑制剂达比加群的抗凝作用，但随后组织型纤溶酶原激活剂治疗的安全性数据仍然很少。在这里，我们回顾了急性缺血性脑卒中患者在全身再灌注治疗前使用达比加群拮抗剂的现有知识。
我们对截至 2017 年 6 月所有发表的达比加群拮抗剂给药后接受静脉内组织型纤溶酶原激活剂治疗的病例进行了系统回顾，并加入了我们自己的 5 个未发表的病例。我们分析了临床和影像学结果、溶栓后症状性颅内出血和其他严重的系统性出血。其他终点包括对依达鲁单抗的过敏反应和急性后期的静脉血栓形成。
我们共确定了 21 例患者（71%为男性），中位年龄为 76 岁（四分位距 70-84 岁）。基线时的国立卫生研究院卒中量表评分中位数为 10 分（n=20，四分位距 5-11 分），20 例患者中有 18 例（90%）为轻度或中度卒中严重程度。从症状发作到开始组织型纤溶酶原激活的时间为 155 分钟（n=18，四分位距 122-214 分钟）。19 例患者中有 3 例（16%）预后不良。1 例患者因溶栓后症状性颅内出血死亡，2 例患者与基线相比，国立卫生研究院卒中量表评分增加。1 例患者发生再发性卒中。未报告有系统性出血、静脉血栓形成或过敏反应。
依达鲁单抗在急性缺血性脑卒中患者中应用于组织型纤溶酶原激活剂治疗的经验有限。在较轻的卒中综合征和较短的时间窗口中，初步临床经验似乎是有利的。需要更大的队列来确认安全性，包括出血并发症和血栓形成的风险。
