VAMPIRE BAT SALIVARY PLASMINOGEN-ACTIVATOR EVOKES MINIMAL BLEEDING RELATIVE TO TISSUE-TYPE PLASMINOGEN-ACTIVATOR AS ASSESSED BY A RABBIT CUTICLE BLEEDING-TIME MODEL

Cuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany t he administration of tissue-type plasminogen activator (tPA) or vampir e bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficaciou s using a rabbit femoral artery thrombosis model (Gardell et al, Circu lation 84:244, 1991). CBT was determined by severing the apex of the n ail cuticle and monitoring the time to cessation of blood flow. CBT wa s minimally elevated (1.6-fold, p=NS) following bolus intravenous admi nistration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasmin ogen and consequent degradation of Factor VIII and fibrinogen. Elevati ons in CBT after the administration of tPA were reversed by the replen ishment of plasma Factor VIII activity to 40% of control, but were una ffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that p romotes thrombolysis, may evoke a minimal bleeding risk, relative to a n equi-efficacious dose of tPA. In addition, the tPA-provoked proteoly tic consumption of Factor VIII may be a key contributor to the heighte ned bleeding risk.