Ultrastructure of ischemic stroke thrombi via scanning electron microscopy: an observational study

Introduction: The mainstay of acute ischemic stroke (AIS) therapy is timely recanalization through either pharmacological thrombolysis using recombinant tissue plasminogen activator (rt-PA), mechanical thrombectomy (MT), or a combination of both. However, due to several contraindications and therapy resistance, rt-PA treatment is effective in only a small number of patients. Furthermore, despite advancements in recanalization rates using MT, a subset of thrombi still display resistance to removal. The precise mechanisms underlying resistance to rt-PA or MT are not completely understood but thrombus composition most likely plays an important role. The aim of this study was to investigate the ultrastructural organization of AIS thrombi using scanning electron microscopy (SEM).

Method: Thrombi from AIS patients were retrieved via MT at AZ Groeninge Hospital (Kortrijk, Belgium). Following fixation, thrombi were halved to allow investigation of both the interior and surface of the thrombus and then further processed for SEM imaging.

Results: SEM imaging of AIS thrombi revealed distinct ultrastructural characteristics. The interior of AIS thrombi is primarily comprised of three distinct thrombus structures: red blood cell (RBC)-rich, platelet-rich and fibrin-rich structures, which vary in quantity and organization within the thrombus. RBC-rich structures exhibit differences in the packing density, ranging from loosely organized RBCs to tightly packed polyhedrocytic RBCs. In densely compacted areas, wire-shaped notches corresponding to the size of individual fibrin fibers can be observed within the RBCs. Platelet-rich regions are characterized by densely compacted structures in which individual components are often fused together, potentially reducing the accessibility of fibrin and its susceptibility to rt-PA. Within the fibrin-rich regions, various morphologies of fibrin networks were observed, including spongy fibrin, branched fibrin and thick fibrin bundles. The surface structure of the thrombus typically differs from its interior; however it is not uniform and varies between different thrombi. Additionally, within a single thrombus, the surface can range from loosely arranged fibrin to much denser and seemingly impermeable platelet aggregates. Occasionally, a distinct envelope was observed, with a thickness varying between approximately 1 µm and 10 µm.

Conclusion: Our SEM study revealed distinct ultrastructural and architectural features in both the surface and interior of AIS stroke thrombi, further enhancing our understanding of their composition.

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Artikel online veröffentlicht:
13. Februar 2025