Details

Autor(en) / Beteiligte

• Cirillo, P.
• Golino, P.
• Ragni, M.
• D'andrea, D.
• Calabró, P.
• Corcione, N.
• Vigorito, F.
• Ravera, M.
• Chiariello, M.

Titel

Long‐lasting antithrombotic effects of a single dose of human recombinant, active site‐blocked factor VII: insights into possible mechanism(s) of action

Ist Teil von

• Journal of thrombosis and haemostasis, 2003-05, Vol.1 (5), p.992-998

Ort / Verlag

Oxford, UK: Blackwell Science Inc

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Tissue factor (TF) is important in initiating intravascular thrombosis. We demonstrated that active‐site blocked factor VII (FVIIai) inhibits intravascular thrombosis for at least 6 h following a single injection, despite FVIIai plasma half‐life was ∼45 min. The aims of the present study were: (a) to determine the duration of the antithrombotic effects of a single injection of FVIIai; and (b) to assess whether FVIIai prolonged effects can be explained by a slow dissociation rate from TF in the arterial wall. Cyclic flow variations (CFVs), obtained in stenotic rabbit carotid arteries with endothelial injury, were abolished by either FVIIai (100 µg kg−1 min−1 for 10 min) or hirudin (1 mg kg−1). After CFVs were abolished, carotid blood flow velocity was recorded continuously for 24 h. CFVs restored in all hirudin‐treated animals after 2.1 ± 0.3 h, while they restored in only four of nine FVIIai‐treated rabbits in 10.1 ± 2.2 h. Five animals in this group did not show restoration of CFVs up to 24 h. Immunohistochemistry revealed that FVIIai was still bound to the arterial wall 24 h following its administration, despite at this time FVIIai plasma levels were undetectable. Prothrombin time and partial thromboplastin time did not change significantly. FVIIai exerts potent, long‐lasting antithrombotic effects without affecting systemic hemostatic parameters; a possible mechanism is a slow dissociation rate of FVIIai from TF. These proprieties make FVIIai particularly attractive as an antithrombotic intervention.