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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 (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 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 Social Bookmarking                   What's this? Submitted September 9, 2002 Accepted October 15, 2002 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 Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands * Corresponding author; email: j.a.lisman{at}azu.nl. A novel approach to treat bleeding episodes in patients with Glanzmann's thrombasthenia (GT) and perhaps also in patients receiving IIb3inhibitors, 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Weeterings, P. G. de Groot, J. Adelmeijer, and T. Lisman The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface Blood, October 15, 2008; 112(8): 3227 - 3233. [Abstract] [Full Text] [PDF] M. Durand, T. Lecompte, M. Hacquard, and J.-P. Carteaux Heparin-induced thrombocytopenia and cardiopulmonary bypass: anticoagulation with unfractionated heparin and the GPIIb/IIIa inhibitor tirofiban and successful use of rFVIIa for post-protamine bleeding due to persistent platelet blockade Eur. J. Cardiothorac. Surg., September 1, 2008; 34(3): 687 - 689. [Abstract] [Full Text] [PDF] 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]

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