Effect of locally-applied active site-blocked activated factor VII (ASIS) on experimental arterial thrombosis

The starting point of blood coagulation in vivo is the formation of a complex between tissue factor (TF), which is exposed following vascular disease or trauma, and activated blood coagulation factor VII (FVIIa). This blinded, random, paired study evaluates whether active site-blocked activated FVII (FVIIai, ASIS), which binds avidly to TF but is unable to initiate the coagulation processes, inhibits experimental thrombosis. Arteriotomy and deep vessel wall trauma were performed in the central arteries of rabbits' ears. The topical administration of ASIS (0.5 mg in 200 microl vehicle) resulted in a distinct antithrombotic effect compared to vehicle alone. Patency rates at 30 and 120 min after reperfusion were 85% and 75% in the ASIS group and 45% and 30% in the vehicle group, respectively (P = 0.008 and P = 0.004). In contrast, intravenous administration of ASIS (4 mg/kg) produced no antithrombotic effect. Arteriotomy bleeding times were 1.5 min in the ASIS group and 2.0 min in the vehicle group (medians, P = 1). Local application of ASIS produces a pronounced antithrombotic effect in rabbits without giving rise to antihaemostatic side-effects. This mode of treatment may have a potential for a variety of clinical interventions in injured or diseased vessels.