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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4346-4353. Prepublished online as a Blood First Edition Paper on January 3, 2006; DOI 10.1182/blood-2005-10-4244. This Article Full Text (PDF) All Versions of this Article: 2005-10-4244v1 107/11/4346    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mangin, P. Articles by Jackson, S. P Search for Related Content PubMed PubMed Citation Articles by Mangin, P. Articles by Jackson, S. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 26, 2005 Accepted December 2, 2005 Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcR receptor deficiency Pierre Mangin, Cindy L Yap, Christelle Nonne, Sharelle A Sturgeon, Isaac Goncalves, Yuping Yuan, Simone M Schoenwaelder, Christine E Wright, Francois Lanza, and Shaun P Jackson* Australian Centre for Blood Diseases, Monash University, Alfred Medical Research & Education Precinct (AMREP), Melbourne, Victoria, Australia Institute National de la Sante et de la Recherche Medicale (INSERM) U.311, Etablissement Francais du Sang, EFS-Alsace, Strasbourg, Alsace, France Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia * Corresponding author; email: shaun.jackson{at}med.monash.edu.au. Fibrillar collagens are amongst the most potent activators of platelets and play an important role in the initiation of thrombosis. The GPVI/FcR-chain complex is a central collagen receptor and inhibitors of GPVI produce a major defect in arterial thrombogenesis. In this study we have examined arterial thrombus formation in mice lacking the GPVI/FcR-chain complex (FcR-/-). Utilising three distinct arterial thrombosis models involving deep vascular injury, we demonstrate that deficiency of GPVI/FcR is not associated with a major defect in arterial thrombus formation. In contrast, with milder vascular injury deficiency of GPVI/FcR was associated with a 30% reduction in thrombus growth. Analysis of FcR-/- platelets in vitro, using thrombin-dependent and -independent thrombosis models, demonstrated a major role for thrombin in overcoming the thrombosis defect associated with GPVI/FcR deficiency. Inhibition of thrombin in vivo produced a much greater defect in thrombus formation in mice lacking GPVI/FcR compared to normal controls. Similarly, thrombin inhibition produced a marked prolongation in bleeding time in FcR-/- mice relative to wild-type mice. Our studies define an important role for thrombin in overcoming the hemostatic and thrombotic defect associated with GPVI/FcR deficiency. Moreover, they raise the interesting possibility that the full antithrombotic potential of GPVI receptor antagonists may only be realized through the concurrent administration of anticoagulant agents. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: GPVI: no magic bullet for thrombosis Mark L. Kahn Blood 2006 107: 4199. [Full Text] [PDF] This article has been cited by other articles: Y. A. Senis, M. G. Tomlinson, S. Ellison, A. Mazharian, J. Lim, Y. Zhao, K. N. Kornerup, J. M. Auger, S. G. Thomas, T. Dhanjal, et al. 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