rFVIIai in Acute Coronary Syndromes

Brit Binow Sorensen; Ulla Hedner; Elisabeth Erhardtsen

doi:10.1055/s-2003-40678

Seminars in Vascular Medicine, Table of Contents

Semin Vasc Med 2003; 03(2): 199-204
DOI: 10.1055/s-2003-40678

rFVIIai in Acute Coronary Syndromes

Brit Binow Sorensen¹ , Ulla Hedner² , Elisabeth Erhardtsen³

¹Haemostasis Biology, Novo Nordisk A/S, Maaløv, Denmark
²NovoSeven Research, Novo Nordisk A/S, Maaløv, Denmark
³Global Development, Biopharmaceuticals Therapy Area,Novo Nordisk A/S, Bagsvaerd, Denmark

Abstract

ABSTRACT

Following vessel wall injury, tissue factor (TF) is exposed and forms complexes with already activated factor VII (FVIIa) present in the circulating blood, thereby initiating the hemostatic process. After the first FXa is formed, the TF pathway inhibitor (TFPI) forms a complex with FXa, and a quaternary complex is formed, TF/FVIIa/ FXa/TFPI, which inhibits the first step of the hemostatic pathway. Recombinant activated FVII (rFVIIa) has been developed for use as a hemostatic agent (NovoNordisk A/S, Denmark). Active site-inactivated rFVIIa (rFVIIai) has also been prepared and was shown to have a faster association to and a slower dissociation from TF than rFVIIa, resulting in a lower calculated Kd of rFVIIai compared with rFVIIa. In various animal models rFVIIai has been demonstrated to prevent or diminish immediate thrombus formation at the site of vessel wall injury (athroplasty or other forms of mechanical injury) as well as the development of long-term intima thickening. The inflammatory response following endotoxin-induced sepsis was shown to decrease after administration of rFVIIai. Also, survival increased in the rFVIIai-treated animals in this study. In addition, ischemia-reperfusion injury was mitigated by rFVIIai. In a limited number of patients undergoing percutaneous transluminal coronary angioplasty (PTCA), rFVIIai was observed to allow PTCA to be performed at lower doses of heparin than what has been reported previously.

KEYWORDS

Tissue factor - inactivated FVIIa - PTCA - endotoxin - reperfusion

Full Text

References

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