Ho-Tin-Noé Benoit, Desilles Jean-Philippe, Mazighi Mikael
Université Paris Cité, Inserm, Optimisation Thérapeutique en Neuropsychopharmacologie, Paris, France.
Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France.
Res Pract Thromb Haemost. 2023 May 16;7(4):100178. doi: 10.1016/j.rpth.2023.100178. eCollection 2023 May.
A State of the Art lecture titled "" was presented at the ISTH Congress in 2022. Intravenous thrombolysis (IVT) remains the only pharmacologic option to re-establish cerebral perfusion at the acute phase of ischemic stroke. IVT is based on the administration of recombinant tissue plasminogen activator with the objective of dissolving fibrin, the major fibrillar protein component of thrombi. Almost 30 years on from its introduction, although the clinical benefits of IVT have been clearly demonstrated, IVT still suffers from a relatively low efficacy, with a rate of successful early recanalization below 50% overall. Analyses of thrombectomy-recovered acute ischemic stroke (AIS) thrombi have shown that apart from occlusion site, thrombus length, and collateral status, AIS thrombus structure and composition are also important modulators of IVT efficacy. In this article, after a brief presentation of IVT principle and current knowledge on IVT resistance, we review recent findings on how compaction and structural alterations of fibrin together with nonfibrin thrombus components such as neutrophil extracellular traps and von Willebrand factor interfere with IVT in AIS. We further discuss how these new insights could soon result in the development of original adjuvant therapies for improved IVT in AIS. Finally, we summarize relevant new data presented during the 2022 ISTH Congress.
一场题为“”的前沿讲座于2022年在国际血栓与止血学会（ISTH）大会上发表。静脉溶栓（IVT）仍然是在缺血性中风急性期重新建立脑灌注的唯一药物选择。IVT基于重组组织型纤溶酶原激活剂的给药，目的是溶解纤维蛋白，血栓的主要纤维状蛋白质成分。自引入近30年来，尽管IVT的临床益处已得到明确证明，但IVT的疗效仍然相对较低，总体早期再通成功率低于50%。对血栓切除术回收的急性缺血性中风（AIS）血栓的分析表明，除了闭塞部位、血栓长度和侧支循环状态外，AIS血栓的结构和组成也是IVT疗效的重要调节因素。在本文中，在简要介绍IVT原理和当前关于IVT抵抗的知识后，我们回顾了关于纤维蛋白的压实和结构改变以及中性粒细胞胞外陷阱和血管性血友病因子等非纤维蛋白血栓成分如何干扰AIS中IVT的最新发现。我们进一步讨论了这些新见解如何可能很快导致开发用于改善AIS中IVT的原创辅助疗法。最后，我们总结了在2022年ISTH大会期间展示的相关新数据。
