Staessens Senna, François Olivier, Desender Linda, Vanacker Peter, Dewaele Tom, Sciot Raf, Vanhoorelbeke Karen, Andersson Tommy, De Meyer Simon F
Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, E. Sabbelaan 53, 8500, Kortrijk, Belgium.
Department of Medical Imaging, AZ Groeninge, Kortrijk, Belgium.
Thromb J. 2021 Feb 22;19(1):11. doi: 10.1186/s12959-021-00262-1.
Mechanical removal of a thrombus by thrombectomy can be quite challenging. For reasons that are not fully understood, some thrombi require multiple passes to achieve successful recanalization, whereas other thrombi are efficiently removed in a single pass. Since first pass success is associated with better clinical outcome, it is important to better understand the nature of thrombectomy resistant thrombi. The aim of this study was therefore to characterize the cellular and molecular composition of a thrombus that was very hard to retrieve via mechanical thrombectomy.
In a patient that was admitted with a right middle cerebral artery M1-occlusion, 11 attempts using various thrombectomy devices and techniques were required for removal of the thrombus. This peculiar case provided a rare opportunity to perform an in-depth histopathological study of a difficult to retrieve thrombus. Thrombus material was histologically analyzed using hematoxylin and eosin, Martius Scarlet Blue stain (red blood cells and fibrin), Feulgen stain (DNA), von Kossa stain (calcifications) and immunohistochemical analysis of von Willebrand factor, platelets, leukocytes and neutrophil extracellular traps. Histological analysis revealed abnormally high amounts of extracellular DNA, leukocytes, von Willebrand factor and calcifications. Extracellular DNA stained positive for markers of leukocytes and NETs, suggesting that a significant portion of DNA is derived from neutrophil extracellular traps.
In this unique case of a nearly thrombectomy-resistant stroke thrombus, our study showed an atypical composition compared to the common structural features found in ischemic stroke thrombi. The core of the retrieved thrombus consisted of extracellular DNA that colocalized with von Willebrand factor and microcalcifications. These results support the hypothesis that von Willebrand factor, neutrophil extracellular traps and microcalcifications contribute to mechanical thrombectomy resistance. Such information is important to identify novel targets in order to optimize technical treatment protocols and techniques to increase first pass success rates.
通过血栓切除术机械清除血栓可能极具挑战性。由于尚未完全明确的原因,一些血栓需要多次操作才能成功再通,而另一些血栓单次操作就能有效清除。由于首次操作成功与更好的临床结果相关,因此更好地了解抗血栓切除术血栓的性质很重要。因此,本研究的目的是对通过机械血栓切除术很难取出的血栓的细胞和分子组成进行表征。
一名因右侧大脑中动脉M1段闭塞入院的患者,为清除血栓需要使用各种血栓切除装置和技术进行11次尝试。这个特殊病例为对难以取出的血栓进行深入组织病理学研究提供了难得的机会。使用苏木精和伊红、马休黄猩红蓝染色(红细胞和纤维蛋白)、福尔根染色(DNA)、冯科萨染色(钙化)对血栓材料进行组织学分析,并对血管性血友病因子、血小板、白细胞和中性粒细胞胞外陷阱进行免疫组织化学分析。组织学分析显示细胞外DNA、白细胞、血管性血友病因子和钙化异常大量存在。细胞外DNA对白细胞和中性粒细胞胞外陷阱的标志物呈阳性染色,表明很大一部分DNA来自中性粒细胞胞外陷阱。
在这个几乎抗血栓切除术的中风血栓的独特病例中,我们的研究显示与缺血性中风血栓中常见的结构特征相比,其组成具有非典型性。取出的血栓核心由与血管性血友病因子和微钙化共定位的细胞外DNA组成。这些结果支持血管性血友病因子、中性粒细胞胞外陷阱和微钙化导致抗机械血栓切除术的假说。这些信息对于识别新靶点以优化技术治疗方案和技术以提高首次操作成功率很重要。