[en] During the last decade, significant progress has been made in understanding thrombus composition and organization in the setting of acute ischemic stroke (AIS). In particular, thrombus organization is now described as highly heterogeneous but with 2 preserved characteristics: the presence of (1) two distinct main types of areas in the core-red blood cell (RBC)-rich and platelet-rich areas in variable proportions in each thrombus-and (2) an external shell surrounding the core composed exclusively of platelet-rich areas. In contrast to RBC-rich areas, platelet-rich areas are highly complex and are mainly responsible for the thrombolysis resistance of these thrombi for the following reasons: the presence of platelet-derived fibrinolysis inhibitors in large amounts, modifications of the fibrin network structure resistant to the tissue plasminogen activator (tPA)-induced fibrinolysis, and the presence of non-fibrin extracellular components, such as von Willebrand factor (vWF) multimers and neutrophil extracellular traps. From these studies, new therapeutic avenues are in development to increase the fibrinolytic efficacy of intravenous (IV) tPA-based therapy or to target non-fibrin thrombus components, such as platelet aggregates, vWF multimers, or the extracellular DNA network.
Disciplines :
Neurology
Author, co-author :
Desilles, Jean-Philippe; Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France ; Laboratory of Vascular Translational Science, U1148 INSERM, Paris, France ; Université Paris Cité, Paris, France ; FHU Neurovasc, Paris, France
Di Meglio, Lucas; Laboratory of Vascular Translational Science, U1148 INSERM, Paris, France
Delvoye, François ; Université de Liège - ULiège > Département des sciences cliniques > Neuroimagerie des troubles de la mémoire et revalidation cognitive ; Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France
Maïer, Benjamin; Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France ; Université Paris Cité, Paris, France ; FHU Neurovasc, Paris, France
Piotin, Michel; Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France ; Laboratory of Vascular Translational Science, U1148 INSERM, Paris, France
Ho-Tin-Noé, Benoît; Laboratory of Vascular Translational Science, U1148 INSERM, Paris, France ; Université Paris Cité, Paris, France
Mazighi, Mikael; Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France ; Laboratory of Vascular Translational Science, U1148 INSERM, Paris, France ; Université Paris Cité, Paris, France ; FHU Neurovasc, Paris, France ; Department of Neurology, Hopital Lariboisère, APHP Nord, Paris, France
Language :
English
Title :
Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies.
INSERM - French Institute of Health and Medical Research [FR] FRM - Fondation pour la Recherche Médicale [FR] ANR - Agence Nationale de la Recherche [FR]
Funding text :
This work was supported by INSERM, La Fondation pour la Recherche sur les AVC (grant # FR-AVC-003), La Fondation pour la Recherche Médicale (grant #DPC20171138959), La Fondation de l'Avenir (AP-RM-17-005), and by a public grant overseen by the French National Research Agency (ANR) as part of the Investments for the Future program (PIA) under grant agreement nos. ANR-18-RHUS-0001 (RHU Booster) and ANR-16-RHUS-0004 (RHU TRT_cSVD).
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