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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-09-2761. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2761v1 101/5/1864    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lisman, T. Articles by De Groot, P. G. Search for Related Content PubMed PubMed Citation Articles by Lisman, T. Articles by De Groot, P. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1864-1870 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Recombinant factor VIIa enhances deposition of platelets with congenital or acquired IIb3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor-independent thrombin generation Ton Lisman, Sultana Moschatsis, Jelle Adelmeijer, H. Karel Nieuwenhuis, and Philip G. De Groot From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht, and Institute of Biomembranes, Utrecht University, Utrecht, the Netherlands. A novel approach to treat bleeding episodes in patients with Glanzmann thrombasthenia (GT) and perhaps also in patients receiving IIb3 inhibitors is the administration of recombinant factor VIIa (rFVIIa). The mechanism of action of rFVIIa in these patients is, however, still unclear. We studied the effect of rFVIIa-mediated thrombin formation on adhesion of IIb3-deficient platelets under flow conditions. Adhesion of IIb3-deficient platelets to the extracellular matrix (ECM) of stimulated human umbilical vein endothelial cells or to collagen type III was studied using a model system with washed platelets and red cells. When IIb3-deficient platelets were perfused over the surface at arterial shear rate for 5 minutes, a low surface coverage was observed (GT platelets, mean ± SEM, 37.5% ± 5.0%; normal platelets preincubated with an RGD-containing peptide, 7.4% ± 2.1%). When rFVIIa, together with factors X and II, was added to the perfusate, platelet deposition significantly increased (GT platelets, mean ± SEM, 67.0% ± 4.3%; normal platelets preincubated with an RGD-containing peptide, 48.2% ± 2.9%). The same effect was observed when normal platelets were pretreated with the commercially available anti-IIb3 drugs abciximab, eptifibatide, or tirofiban. It was shown that tissue factor-independent thrombin generation (presumably induced by binding of rFVIIa to adhered platelets) was responsible for the increase in platelet deposition. In conclusion, defective adhesion of IIb3-deficient platelets to ECM can be restored by tissue factor-independent rFVIIa-mediated thrombin formation. The enhanced generation of platelet procoagulant surface facilitates fibrin formation, so that lack of platelet aggregate formation might be compensated for. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. J. J. Hulstein, P. J. Lenting, B. de Laat, R. H. W. M. Derksen, R. Fijnheer, and P. G. de Groot {beta}2-Glycoprotein I inhibits von Willebrand factor dependent platelet adhesion and aggregation Blood, September 1, 2007; 110(5): 1483 - 1491. [Abstract] [Full Text] [PDF] T. Lisman, N. Raynal, D. Groeneveld, B. Maddox, A. R. Peachey, E. G. Huizinga, P. G. de Groot, and R. W. Farndale A single high-affinity binding site for von Willebrand factor in collagen III, identified using synthetic triple-helical peptides Blood, December 1, 2006; 108(12): 3753 - 3756. [Abstract] [Full Text] [PDF] J. J. J. Hulstein, P. G. de Groot, K. Silence, A. Veyradier, R. Fijnheer, and P. J. Lenting A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B Blood, November 1, 2005; 106(9): 3035 - 3042. [Abstract] [Full Text] [PDF] A. Verrijckt, F. Proulx, S. Morneau, and S. Vobecky Activated recombinant factor VII for refractory bleeding during extracorporeal membrane oxygenation J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1812 - 1813. [Full Text] [PDF] T. Lisman, J. Adelmeijer, H. F. G. Heijnen, and P. G. de Groot Recombinant factor VIIa restores aggregation of {alpha}IIb{beta}3-deficient platelets via tissue factor-independent fibrin generation Blood, March 1, 2004; 103(5): 1720 - 1727. [Abstract] [Full Text] [PDF] D. W. Branch and G. M. Rodgers Recombinant Activated Factor VII: A New Weapon in the Fight Against Hemorrhage Obstet. Gynecol., June 1, 2003; 101(6): 1155 - 1156. [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020