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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1350-1355. Prepublished online as a Blood First Edition Paper on May 18, 2004; DOI 10.1182/blood-2004-03-0896. This Article Full Text (PDF) All Versions of this Article: 2004-03-0896v1 104/5/1350    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 Boylan, B. Articles by Newman, P. J Search for Related Content PubMed PubMed Citation Articles by Boylan, B. Articles by Newman, P. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2004 Accepted April 19, 2004 Anti-GPVI-associated ITP: An acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcR-chain complex from the human platelet surface Brian Boylan, Hong Chen, Vipul Rathore, Cathy Paddock, Michael Salacz, Kenneth D Friedman, Brian R Curtis, Michelle Stapleton, Debra K Newman, Mark L Kahn, and Peter J Newman* Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA Division of Cardiology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA Medicine, Medical College of Wisconsin, Milwaukee, WI, USA Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Medicine, Medical College of Wisconsin, Milwaukee, WI, USA Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Microbiology, Medical College of Wisconsin, Milwaukee, WI, USA Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA; Cellular Biology, Medical College of Wisconsin, Milwaukee, WI, USA; Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA * Corresponding author; email: pjnewman{at}bcsew.edu. Platelet glycoprotein (GP) VI is a 62 kDa membrane glycoprotein that exists on both human and murine platelets in a non-covalent complex with the Fc receptor (FcR) chain. The GPVI/FcR chain complex serves as the major activating receptor for collagen, as evidenced by observations that platelets genetically-deficient in GPVI or the FcR-chain are highly refractory to collagen-induced platelet activation. Recently, several different rat anti-murine GPVI monoclonal antibodies, termed JAQs 1, 2, and 3, were produced that had the unique property of immuno-depleting GPVI from the murine platelet surface and rendering them unresponsive to collagen or GPVI-specific agonists like convulxin or collagen-related peptide (CRP). Herein, we describe a patient with a mild bleeding disorder and a moderately-reduced platelet count whose platelets fail to become activated in response to collagen or CRP, and inefficiently adhere to and form thrombi on immobilized collagen under conditions of arterial shear. Though the amount of GPVI platelet mRNA and the nucleotide sequence of the GPVI gene were found to be normal, both GPVI and the FcR-chain were nearly absent from the platelet surface, and were markedly reduced in whole platelet detergent lysates. Patient plasma contained an autoantibody that bound specifically to GPVI-positive, normal platelets, and cleared soluble GPVI from her plasma, suggesting that that the patient suffers from a rare form of idiopathic thrombocytopenic purpura caused by a GPVI-specific autoantibody that mediates clearance of the GPVI/FcR-chain complex from the platelet surface. Since antibody-induced GPVI shedding has now been demonstrated in both humans and mice, these studies may provide a rationale for developing therapeutic reagents that induce temporary depletion of GPVI for the treatment of clinical thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Falet, M. P. Marchetti, K. M. Hoffmeister, M. J. Massaad, R. S. Geha, and J. H. Hartwig Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP Blood, November 19, 2009; 114(21): 4729 - 4737. [Abstract] [Full Text] [PDF] B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. Newman Identification of Fc{gamma}RIIa as the ITAM-bearing receptor mediating {alpha}IIb{beta}3 outside-in integrin signaling in human platelets Blood, October 1, 2008; 112(7): 2780 - 2786. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. 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