Lvm. Rao et M. Ezban, Active site-blocked activated factor VII as an effective antithrombotic agent: mechanism of action, BL COAG FIB, 11, 2000, pp. S135-S143
The tissue factor (TF) coagulation pathway is initiated when circulating fa
ctor (F)VII(a) encounters TF, a cell surface glycoprotein, as a result of v
ascular injury or pathological perturbation. TF-induced coagulation plays a
primary role in hemostasis and also in the pathogenesis of various thrombo
tic disorders. Recent studies suggest that activation of the TF-pathway may
also contribute to other pathophysiological processes by altering intracel
lular responses, either directly or via activated factor X (Dia) and thromb
in generation. Therefore, suppression of the aberrant expression of TF/FVII
a on cell surfaces not only prevents thrombotic disorders but may also prov
ide other protective effects. Recent ex-vivo and in-vivo experiments docume
nt the effectiveness of active site-blocked activated factor VII(FVIIai) in
inhibiting TF-mediated injury. It is generally believed that FVIIai exerts
its effects by limiting the formation of functional TF/FVIIa complexes by
directly competing with plasma FVII(a) for Limited available TF sites on ce
ll surfaces. Although such competition can explain the effectiveness of FVI
Iai immediately after administration, it is not clear how it exerts its pro
longed effects. In this manuscript, we summarize the use of FVIIai as an an
tithrombotic agent in various model systems and discuss potential mechanism
s by which FVIIai may exert protective effects. Blood Coagul Fibrinolysis 1
1 (suppl 1):S135-S143 (C) 2000 Lippincott Williams & Wilkins.