Antithrombotic and antilesion benefits without hemorrhagic risks by inhibiting tissue factor pathway.
The effects of inhibiting tissue factor-dependent thrombus formation on vascular neointimal lesion formation have been evaluated by inhibiting tissue factor activity using intravenous injections of active-site inactivated recombinant factor VIIa (FVIIai) administered to baboons immediately prior to initiating bilateral femoral balloon artery angioplasty and surgical carotid endarterectomy. FVIIai abolished thrombus formation at sites of vascular injury and decreased vascular lesion formation by approximately 50 percent at 30 days. We conclude that thrombus formation at sites of vascular injury is predominately tissue factor-dependent and that transient inhibition of tissue factor activity prevents both vascular thrombosis and vascular lesion formation, which implies that transiently inhibiting tissue factor at the time of elective mechanical vascular procedures may be useful in reducing clinical restenosis.
Division of Hematology and Oncology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
L A
LA
Harker
S R
SR
Hanson
J N
JN
Wilcox
A B
AB
Kelly
D000595:Amino Acid Sequence; D001241:Aspirin / Q000627:therapeutic use; D004351:Drug Resistance; D015942:Factor VIIa / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D013925:Thromboplastin; D015942:Factor VIIa; D001241:Aspirin