SEARCH:   Advanced

Blood, 15 October 2008, Vol. 112, No. 8, pp. 3227-3233. Prepublished online as a Blood First Edition Paper on July 8, 2008; DOI 10.1182/blood-2008-02-139113. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-139113v1 112/8/3227    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 Weeterings, C. Articles by Lisman, T. Search for Related Content PubMed PubMed Citation Articles by Weeterings, C. Articles by Lisman, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 14, 2008 Accepted July 1, 2008 The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface Cees Weeterings, Philip G de Groot, Jelle Adelmeijer, and Ton Lisman* Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, Netherlands Institute of Biomembranes, Utrecht University, Utrecht, Netherlands Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, Netherlands * Corresponding author; email: j.a.lisman{at}chir.umcg.nl. Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor (TF)-independent manner. We hypothesized that besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we showed that, in an ELISA set-up, a purified extracellular fragment of GPIb bound to immobilized rFVIIa. Surface plasmon resonance established a Kd of about 20 nM for this interaction. In addition, CHO cells transfected with the GPIb-IX-V complex could adhere to immobilized rFVIIa, whereas wild-type CHO cells could not. Furthermore, platelets stimulated with a combination of collagen and thrombin adhered to immobilized rFVIIa under static conditions. Platelet adhesion was inhibited by treatment with O-sialoglycoprotein endopeptidase (OSE), which cleaves GPIb from the platelet surface. In addition, rFVIIa-mediated thrombin generation on the activated platelet surface was inhibited by cleaving GPIb from its surface. In summary, three lines of evidence showed that rFVIIa interacts with the GPIb-IX-V complex, and this interaction enhanced TF-independent thrombin generation mediated by rFVIIa on the activated platelet surface. The rFVIIa-GPIb interaction could contribute to cessation of bleeding after administration of rFVIIa to patients with bleeding disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FVIIa: you've come a long way, baby! Maureane Hoffman Blood 2008 112: 3002-3003. [Full Text] [PDF] This article has been cited by other articles: T. Lisman Factor XI Binding to Platelets: Glycoprotein Ib{alpha} Has an Accomplice Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1409 - 1410. [Full Text] [PDF] E. Guyot, A. Carillion, M.-L. Poli-Merol, I. Ferrand, C. Amory, D. Chaoudi, S. Poret, and J.-M. Malinovsky Ehlers-Danlos syndrome type IV in a child admitted in emergency with peritonitis Br. J. Anaesth., October 1, 2009; 103(4): 615 - 616. [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020