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dc.contributor.authorInduruwa, Isuru
dc.contributor.authorMcKinney, Harriet
dc.contributor.authorKempster, Carly
dc.contributor.authorThomas, Patrick
dc.contributor.authorBatista, Joana
dc.contributor.authorMalcor, Jean-Daniel
dc.contributor.authorBonna, Arkadiusz
dc.contributor.authorMcGee, Joanne
dc.contributor.authorBumanlag-Amis, Elaine
dc.contributor.authorRehnstrom, Karola
dc.contributor.authorAshford, Sophie
dc.contributor.authorSoejima, Kenji
dc.contributor.authorOuwehand, Willem
dc.contributor.authorFarndale, Richard
dc.contributor.authorDownes, Kate
dc.contributor.authorWarburton, Elizabeth
dc.contributor.authorMoroi, Masaaki
dc.contributor.authorJung, Stephanie
dc.description.abstractOBJECTIVES: Platelet activation underpins thrombus formation in ischemic stroke. The active, dimeric form of platelet receptor glycoprotein (GP) VI plays key roles by binding platelet ligands collagen and fibrin, leading to platelet activation. We investigated whether patients presenting with stroke expressed more GPVI on their platelet surface and had more active circulating platelets as measured by platelet P-selectin exposure. METHODS: 129 ischemic or hemorrhagic stroke patients were recruited within 8h of symptom onset. Whole blood was analyzed for platelet-surface expression of total GPVI, GPVI-dimer, and P-selectin by flow cytometry at admission and day-90 post-stroke. Results were compared against a healthy control population (n = 301). RESULTS: The platelets of stroke patients expressed significantly higher total GPVI and GPVI-dimer (P<0.0001) as well as demonstrating higher resting P-selectin exposure (P<0.0001), a measure of platelet activity, compared to the control group, suggesting increased circulating platelet activation. GPVI-dimer expression was strongly correlated circulating platelet activation [r2 = 0.88, P<0.0001] in stroke patients. Furthermore, higher platelet surface GPVI expression was associated with increased stroke severity at admission. At day-90 post-stroke, GPVI-dimer expression and was further raised compared to the level at admission (P<0.0001) despite anti-thrombotic therapy. All ischemic stroke subtypes and hemorrhagic strokes expressed significantly higher GPVI-dimer compared to controls (P<0.0001). CONCLUSIONS: Stroke patients express more GPVI-dimer on their platelet surface at presentation, lasting at least until day-90 post-stroke. Small molecule GPVI-dimer inhibitors are currently in development and the results of this study validate that GPVI-dimer as an anti-thrombotic target in ischemic stroke.
dc.description.sponsorshipBritish Heart Foundation, SP/13/7/30575, Dr Stephanie M Jung British Heart Foundation, RE/13/6/30180, Dr Isuru Induruwa NIHR CL to Dr Isuru Induruwa
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.titlePlatelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results.
dc.publisher.departmentDepartment of Medicine
prism.publicationNamePLoS One
dc.contributor.orcidInduruwa, Isuru [0000-0002-7020-8179]
dc.contributor.orcidFarndale, Richard [0000-0001-6130-8808]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (Unknown)
cam.orpheus.successTue Feb 01 19:02:38 GMT 2022 - Embargo updated*
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International