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Semin Thromb Hemost 2006; 32: 077-085
DOI: 10.1055/s-2006-939557
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Mechanism of Action of Factor VIIa in the Treatment of Coagulopathies

Ulla Hedner1 , 2
  • 1University of Lund, Malmö, Sweden
  • 2Research & Development, Novo Nordisk A/S, Bagsvaerd, Denmark
Further Information

Publication History

Publication Date:
02 May 2006 (online)

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ABSTRACT

Recombinant factor VIIa (rFVIIa) has been developed for treatment of bleeding in patients with hemophilia who have inhibitors against factor VIII (FVIII) or FIX, and has been found to induce hemostasis during major orthopedic surgery. The use of rFVIIa treatment for hemophilia is a new concept and is based on the low-affinity binding of FVIIa to the surface of thrombin-activated platelets. Administration of pharmacologic doses of exogenous rFVIIa enhances thrombin generation on the platelet surface at the site of injury independently of the presence of FVIII or FIX. Pharmacologic doses of rFVIIa induce hemostasis not only in hemophilia patients, but also in patients with thrombocytopenia, functional platelet defects, and with profuse bleeding triggered by extensive surgery or trauma. The general mechanism of action of rFVIIa to induce hemostasis under these conditions may be its capacity to generate a tight fibrin hemostatic plug through increased thrombin generation. A tight fibrin plug will aid in resisting the overwhelming local release of fibrinolytic activity triggered by vast tissue damage occurring in extensive trauma. Local fibrinolytic activity also occurs in the gastrointestinal tract as well as during profuse postpartum bleeding. Pharmacologic doses of rFVIIa induce hemostasis in these cases also.

KEYWORDS

Recombinant factor VIIa - hemophilia - bleeding disorders - thrombin generation - posttraumatic bleeding

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Ulla HednerM.D. Ph.D. 

Professor, University of Lund, Caritasgatan 19

SE-218 20 Malmö, Sweden

Email: UHe@novonordisk.com

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