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International Journal of
HEMATOLOGY
Review Article
Recombinant Factor VIIa: A Review on Its Clinical Use
Massimo Franchini
Servizio di Immunoematologia e Trasfusione Centro Emolia, Azienda Ospedaliera di Verona, Verona, Italy
Received July 27, 2005; received in revised form November 3, 2005; accepted November 8, 2005
Abstract
Recombinant activated factor VII (rFVIIa) (NovoSeven) is a novel hemostatic agent originally developed to treat bleeding episodes in hemophilic patients with inhibitors against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired hemostatic abnormalities. Based on a literature search including PubMed, references from reviews, and abstracts from the most important meetings on this topic, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterized clinical applications.
Int J Hematol. 2006;83:126-138. doi: 10.1532/IJH97.E05172006 The Japanese Society of Hematology
Key words: Recombinant FVIIa; Bleeding; Hemophilia; Inhibitors; Trauma; Surgery
1. Introduction
Recombinant activated factor VII (rFVIIa) (NovoSeven; Novo Nordisk Pharmaceuticals, Bagsvrd, Denmark) was originally developed for the treatment of hemophilic patients with inhibitors and then used successfully for treating hemorrhages in patients with acquired hemophilia [1-6]. In the last few years, along with the improvement in the knowledge of its mechanisms of action, rFVIIa has also been used with benet as a universal hemostatic agent in many other nonhemophilic bleeding situations, including congenital FVII deciencies, quantitative and qualitative platelet disorders, hepatic failure, liver transplantation, major surgery, and trauma [7-12]. This review briey analyzes the clinical experience regarding rFVIIa treatment and focuses particularly on the newer uses, for which there are only a few randomized, controlled clinical trials. Table 1 summarizes the current approved and off-label clinical applications of rFVIIa.
2. Mechanisms of Action of rFVIIa
FVIIa is an important contributor to the initiation of hemostasis [12]. According to a cell-based model of coagula-
Correspondence and reprint requests: Dr. Massimo Franchini, MD, Servizio di Immunoematologia e Trasfusione Centro Emolia, Ospedale Policlinico, Piazzale Ludovico Scuro, 37134 Verona, Italy; 0039-045-8074321; fax: 0039-045-8074626 (e-mail: [email protected]).
tion [13,14], tissue factor (TF) is exposed to circulating blood following injury to the vessel wall, and TF-FVIIa complexes are formed on the TF-bearing cells, where they activate factor X (FX) to produce...