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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 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 Citation Map 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 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 Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The glycoprotein Ib-IX-V complex contributes to tissue factor–independent thrombin generation by recombinant factor VIIa on the activated platelet surface Cees Weeterings1,2, Philip G. de Groot1,2, Jelle Adelmeijer3, and Ton Lisman13 1 Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht; 2 Institute of Biomembranes, Utrecht University, Utrecht; and 3 Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-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 setup, a purified extracellular fragment of GPIb bound to immobilized rFVIIa. Surface plasmon resonance established a affinity constant (Kd) of approximately 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 sti-mulated with a combination of collagen and thrombin adhered to immobilized rFVIIa under static conditions. Platelet adhesion was inhibited by treatment with O-sialoglycoprotein endopeptidase, which specifically 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, 3 lines of evidence showed that rFVIIa interacts with the GPIb-IX-V complex, and this interaction enhanced tissue factor-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]

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