{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:12:35Z","timestamp":1793448755460,"version":"4.5.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Shear-induced platelet aggregation (SIPA) occurs under elevated shear rates (10\u2009000 s\u22121) found in stenotic coronary and carotid arteries. The pathologically high shear environment can lead to occlusive thrombosis by SIPA from the interaction of nonactivated platelets and von Willebrand factor (VWF) via glycoprotein Ib\u2013A1 binding. This process under high shear rates is difficult to visualize experimentally with concurrent molecular- and cellular-resolutions. To understand this fast bonding, we employ a validated multiscale in silico model incorporating measured molecular kinetics and a thrombosis-on-a-chip device to delineate the flow-mediated biophysics of VWF and platelets assembly into mural microthrombi. We show that SIPA begins with VWF elongation, followed by agglomeration of platelets in the flow by soluble VWF entanglement before mural capture of the agglomerate by immobilized VWF. The entire SIPA process occurs on the order of 10 milliseconds with the agglomerate traveling a lag distance of a few hundred microns before capture, matching in\u00a0vitro results. Increasing soluble VWF concentration by \u223c20 times in silico leads to a \u223c2 to 3 times increase in SIPA rates, matching the increase in occlusion rates found in\u00a0vitro. The morphology of mural aggregates is primarily controlled by VWF molecular weight (length), where normal-length VWF leads to cluster or elongated aggregates and ultra-long VWF leads to loose aggregates seen by others\u2019 experiments. Finally, we present phase diagrams of SIPA, which provides biomechanistic rationales for a variety of thrombotic and hemostatic events in terms of platelet agglomeration and capture.<\/jats:p>","DOI":"10.1182\/bloodadvances.2021005692","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T17:01:13Z","timestamp":1640106073000},"page":"2453-2465","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":49,"title":["SIPA in 10 milliseconds: VWF tentacles agglomerate and capture platelets under high shear"],"prefix":"10.1182","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-450X","authenticated-orcid":false,"given":"Zixiang Leonardo","family":"Liu","sequence":"first","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, and"},{"name":"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4967-624X","authenticated-orcid":false,"given":"Christopher","family":"Bresette","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-6040","authenticated-orcid":false,"given":"Cyrus K.","family":"Aidun","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, and"},{"name":"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-8004","authenticated-orcid":false,"given":"David N.","family":"Ku","sequence":"additional","affiliation":[{"name":"Parker H. 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