Mechanism of action of recombinant activated factor VII: an update.
Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.
Hedner
Ulla
U
University of Lund, Sweden. UHE@novonordisk.com
D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005167:Factor VII / Q000378:metabolism* / Q000627:therapeutic use; D015942:Factor VIIa; D005173:Factor XI Deficiency / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013917:Thrombin / Q000378:metabolism*
D011994:Recombinant Proteins; D005167:Factor VII; D005337:Fibrin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin