Thalerová Sandra, Pešková Michaela, Kittová Patrícia, Gulati Sumeet, Víteček Jan, Kubala Lukáš, Mikulík Robert
Neurology Department, International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia.
Institute of Biophysics of the Czech Academy of Sciences, Brno, Czechia.
Front Pharmacol. 2021 Sep 15;12:740930. doi: 10.3389/fphar.2021.740930. eCollection 2021.
Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase . Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban; compared to those with apixaban had alteplase-induced mass loss 54 ± 8% vs. 53 ± 8%, = 1.00; RBC release 0.14 ± 0.04 vs. 0.12 ± 0.04, = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium. In the flow model, clot lysis without apixaban; compared to those with apixaban was as follows: recanalization time 107 ± 46 min vs. 127 ± 31 min, = 1.00; recanalization frequency 90 ± 22% vs. 90 ± 22%, = 1.00; clot volume reduction 32 ± 15% vs. 34 ± 10%, = 1.00; RBC release 0.029 ± 0.007 vs. 0.022 ± 0.007, = 0.16, respectively. Apixaban had no positive effect on alteplase-induced thrombolysis in both the static and flow models. Our data support current clinical practice, such that thrombolysis is contraindicated in stroke treatment for patients who have been treated with anticoagulants.
急性中风且正在接受抗凝治疗的患者接受溶栓治疗的益处尚未得到充分探讨。本研究的目的是调查阿哌沙班是否会改变阿替普酶的溶栓效果。使用了静态和流动模型以及两种红细胞(RBC)为主的血栓变体,分别含和不含阿哌沙班。血栓由健康人类供体的血液制备,随后接受阿替普酶治疗。阿哌沙班和阿替普酶均采用临床相关浓度。静态模型中的血栓溶解通过血栓重量和分光光度法测定红细胞释放来确定。流动模型中的血栓溶解通过测量再通时间、血栓长度和分光光度法测定红细胞释放来确定。在静态模型中,不含阿哌沙班的血栓与含阿哌沙班的血栓相比,阿替普酶诱导的质量损失分别为54±8% 对53±8%,P = 1.00;红细胞释放分别为0.14±0.04对0.12±0.04,P = 0.14。如果使用血浆代替生理缓冲盐水作为孵育介质,也会得到非常相似的结果。在流动模型中,不含阿哌沙班的血栓溶解与含阿哌沙班的血栓相比情况如下:再通时间107±46分钟对127±31分钟,P = 1.00;再通频率90±22%对90±22%,P = 1.00;血栓体积减少32±15%对34±10%,P = 1.00;红细胞释放分别为0.029±0.007对0.022±0.007,P = 0.16。在静态和流动模型中,阿哌沙班对阿替普酶诱导的溶栓均无积极作用。我们的数据支持当前临床实践,即在中风治疗中,接受抗凝治疗的患者禁忌进行溶栓治疗。