Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI
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montague, samantha; Delierneux, Céline; Lecut, Christelle; Layios, Nathalie; Lee, Christine; Dinsdale, Robert J.; Poulter, Natalie; Andrews, R.K.; Hampson, Peter; Wearn, Christopher M.; Maes, Nathalie; Bishop, Jonathan; Gardiner, Elizabeth
Description
Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked...[Show more]
dc.contributor.author | montague, samantha | |
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dc.contributor.author | Delierneux, Céline | |
dc.contributor.author | Lecut, Christelle | |
dc.contributor.author | Layios, Nathalie | |
dc.contributor.author | Lee, Christine | |
dc.contributor.author | Dinsdale, Robert J. | |
dc.contributor.author | Poulter, Natalie | |
dc.contributor.author | Andrews, R.K. | |
dc.contributor.author | Hampson, Peter | |
dc.contributor.author | Wearn, Christopher M. | |
dc.contributor.author | Maes, Nathalie | |
dc.contributor.author | Bishop, Jonathan | |
dc.contributor.author | Gardiner, Elizabeth | |
dc.date.accessioned | 2019-09-29T23:44:33Z | |
dc.date.available | 2019-09-29T23:44:33Z | |
dc.identifier.issn | 2473-9537 | |
dc.identifier.uri | http://hdl.handle.net/1885/172045 | |
dc.description.abstract | Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28- and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 5′-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients. | |
dc.description.sponsorship | The research was part funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre. The authors also thank the Scar Free Foundation and the British Heart Foundation for funding. S.P.W. holds a BHF Chair (CH/03/003/15571). This project was initiated during a sabbatical visit by E.E.G. supported by the Institute for Advanced Studies at the University of Birmingham. The project was also supported by funding from National Health and Medical Research Council Australia and the Fonds National pour la Recherche Scientifique Belgium (FNRS-FRSM 3.4611.11, CDR J.0043.13) and by the French Community of Belgium (FSRC-12/13, ARC-SF 12/14-05). C.L. was a postdoctoral researcher at the FNRS. C.D. was supported by a “Fond pour la recherche industrielle et agricole” fellowship. C.O. is a senior research associate at the Fonds National pour la Recherche Scientifique. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | American Society of Hematology | |
dc.rights | © 2018 The American Society of Hematology | |
dc.source | Blood Advances | |
dc.title | Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 2 | |
dcterms.dateAccepted | 2017-12-13 | |
dc.date.issued | 2017 | |
local.identifier.absfor | 060110 - Receptors and Membrane Biology | |
local.identifier.absfor | 090303 - Biomedical Instrumentation | |
local.identifier.absfor | 060106 - Cellular Interactions (incl. Adhesion, Matrix, Cell Wall) | |
local.identifier.ariespublication | u1029610xPUB126 | |
local.type.status | Published Version | |
local.contributor.affiliation | Montague, Samantha, College of Health and Medicine, ANU | |
local.contributor.affiliation | Delierneux, Celine, University of Liege | |
local.contributor.affiliation | Lecut, Christelle, University Hospital of Liege | |
local.contributor.affiliation | Layios, Nathalie, University Hospital of Liege | |
local.contributor.affiliation | Lee, Christine, College of Health and Medicine, ANU | |
local.contributor.affiliation | Dinsdale, Robert J., University of Birmingham | |
local.contributor.affiliation | Poulter, N. S., University of Birmingham | |
local.contributor.affiliation | Andrews, R.K. , Monash University | |
local.contributor.affiliation | Hampson, Peter, University of Birmingham | |
local.contributor.affiliation | Wearn, Christopher M., University of Birmingham | |
local.contributor.affiliation | Maes, Nathalie, University Hospital of Liege | |
local.contributor.affiliation | Bishop, Jonathan, University of Birmingham | |
local.contributor.affiliation | Gardiner, Elizabeth, College of Health and Medicine, ANU | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1042865 | |
local.bibliographicCitation.issue | 3 | |
local.bibliographicCitation.startpage | 240 | |
local.bibliographicCitation.lastpage | 251 | |
local.identifier.doi | 10.1182/bloodadvances.2017011171 | |
local.identifier.absseo | 920102 - Cancer and Related Disorders | |
dc.date.updated | 2019-04-21T08:24:11Z | |
dcterms.accessRights | Open Access | |
dc.provenance | http://www.bloodadvances.org/page/authors/copyright-information..."As the open-access journal of the American Society of Hematology, Blood Advances makes the full text of every article published in the journal immediately accessible online, http://www.bloodadvances.org." (as at 27/9/19) | |
Collections | ANU Research Publications |
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