{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:42:40Z","timestamp":1787766160157,"version":"build-2784847793"},"reference-count":24,"publisher":"American Society of Hematology","issue":"4","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,24]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Rare thrombotic events associated with ChAdOx1 nCoV-19 (ChAdOx1) vaccination have raised concerns; however, the underlying mechanisms remain elusive. Here, we report a novel biophysical mechanism by which ChAdOx1 directly interacts with platelets under arterial shear conditions, potentially contributing to postvaccination arterial thrombosis. Using microfluidic post assays, we demonstrate that ChAdOx1 induces shear-dependent platelet aggregation, distinct from conventional von Willebrand factor\u2013mediated adhesion. This interaction is mediated by platelet integrin \u03b1IIb\u03b23 and requires biomechanical activation, explaining the absence of significant binding under static conditions. Molecular dynamics simulations and docking studies reveal preferential binding of ChAdOx1's penton arginine-glycine-aspartic acid (RGD) motif to the activated conformation of \u03b1IIb\u03b23. Inhibiting integrin \u03b1IIb\u03b23 completely abolishes ChAdOx1-induced platelet aggregation, whereas blocking glycoprotein (GP) Ib has minimal effect, confirming a mechanism that bypasses the conventional GPIb-dependent platelet adhesion pathway. Mutagenesis of the RGD motif to AAA eliminates platelet binding, verifying the specificity of this interaction. These findings provide a potential explanation for the association between ChAdOx1 vaccination and arterial thrombotic events, distinct from vaccine-induced immune thrombotic thrombocytopenia. Our results highlight the importance of considering biomechanical factors in vaccine-related thrombotic complications and suggest that shear-dependent integrin activation may be another determinant in the pathogenesis of these rare adverse events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024027675","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:44:01Z","timestamp":1747151041000},"page":"496-503","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["Shear-dependent platelet aggregation by ChAdOx1 nCoV-19 vaccine: a novel biophysical mechanism for arterial thrombosis"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1106-6614","authenticated-orcid":false,"given":"Yiyao Catherine","family":"Chen","sequence":"first","affiliation":[{"name":"1School of Biomedical Engineering, The University of Sydney, Darlington, NSW, 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University of Sydney, Camperdown, NSW, Australia"},{"name":"4Heart Research Institute, Newtown, NSW, Australia"},{"name":"5The University of Sydney Nano Institute, The University of Sydney, Camperdown, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Dupuy","sequence":"additional","affiliation":[{"name":"1School of Biomedical Engineering, The University of Sydney, Darlington, NSW, Australia"},{"name":"3Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia"},{"name":"5The University of Sydney Nano Institute, The University of Sydney, Camperdown, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Moldovan","sequence":"additional","affiliation":[{"name":"1School of Biomedical Engineering, The University of Sydney, Darlington, NSW, Australia"},{"name":"3Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia"},{"name":"4Heart Research Institute, 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