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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1720-1727. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-07-2287. This Article Full Text (PDF) All Versions of this Article: 2003-07-2287v1 103/5/1720    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 July 8, 2003 Accepted October 21, 2003 Recombinant factor VIIa restores aggregation of IIb3-deficient platelets via tissue factor-independent fibrin generation Ton Lisman*, Jelle Adelmeijer, Harry F G Heijnen, and Philip G de Groot Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre, Utrecht, The Netherlands * Corresponding author; email: j.a.lisman{at}azu.nl. Recombinant factor VIIa (rFVIIa) is a safe and effective pro-haemostatic drug for patients with Glanzmann Thrombasthenia (GT). However, the mechanism of action of rFVIIa in these patients is still unclear. Although patients with GT are characterized by a complete absence of platelet aggregation to a variety of agonists, it has been shown that GT platelets are able to form aggregates provided polymerizing fibrin is present. We studied the effect of rFVIIa-mediated fibrin formation on aggregation of IIb3-deficient platelets. When washed platelets from GT patients, or platelets from healthy volunteers treated with an RGD-containing peptide were activated with collagen in the presence of rFVIIa and purified coagulation factors X, II, and fibrinogen, complete aggregation occurred after a lag-phase. Fibrin generation proceeded via rFVIIa-mediated thrombin generation on the activated platelet surface independently of tissue factor. Electron microscopic analysis of IIb3-independent platelet aggregates showed a densely packed structure suggestive of a true platelet-fibrin interaction and not via trapping of platelets into a fibrin network. Also, rFVIIa-mediated IIb3-independent aggregation was demonstrated under conditions of flow using a collagen-coated surface. In conclusion, the efficacy of rFVIIa in GT patients might be explained by induction of IIb3-independent platelet aggregation which compensates the lack of IIb3-dependent aggregation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. A. Tanaka, T. Taketomi, F. Szlam, A. Calatzis, and J. H. Levy Improved Clot Formation by Combined Administration of Activated Factor VII (NovoSeven(R)) and Fibrinogen (Haemocomplettan(R) P) Anesth. Analg., March 1, 2008; 106(3): 732 - 738. [Abstract] [Full Text] [PDF] H. R. Roberts, D. M. Monroe, and G. C. White The use of recombinant factor VIIa in the treatment of bleeding disorders Blood, December 15, 2004; 104(13): 3858 - 3864. [Abstract] [Full Text] [PDF] T. Lisman, J. Adelmeijer, S. Cauwenberghs, E. C.M. van Pampus, J. W.M. Heemskerk, and P. G. de Groot Recombinant Factor VIIa Enhances Platelet Adhesion and Aggregation under Flow Conditions at Normal and Reduced Platelet Count. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 2618 - 2618. [Abstract]

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