M Montoney1, S J Gardell, V J Marder. 1. Department of Medicine, University of Rochester (NY) School of Medicine and Dentistry 14642.
Abstract
BACKGROUND: Vampire bat salivary plasminogen activator (Bat-PA) has significantly greater fibrin specificity than any of the fibrinolytic agents currently in clinical use. This study tests the hypothesis that avoiding fibrinogen depletion may protect against the hemorrhage induced by plasminogen activator treatment. METHODS AND RESULTS: Bat-PA was compared with tissue-type plasminogen activator (TPA) in a randomized, prospective, and blinded study using a rabbit ear puncture model of fibrinolytic bleeding. The two agents were used at equimolar dosages (42 nmol/kg) that yielded similar thrombolytic efficacies in a rabbit femoral artery thrombosis model. Both Bat-PA and TPA prolong primary bleeding to double the baseline values, from between 2.1 and 2.3 minutes to between 4.8 and 5.2 minutes. Rebleeding from hemostatically stable sites during the 3-hour observation period occurred equally often with Bat-PA and TPA, 31% from preinjection sites and 23% to 25% from postinjection sites. The lag time between the time of plasminogen activator injection and the onset of rebleeding was likewise the same for both agents, most occurring at 41 to 57 minutes. However, a greater number of prolonged primary or rebleeding occurrences continued for longer than 10 minutes (63% versus 36%) or longer than 30 minutes (30% versus 10%) after Bat-PA than TPA injection. Animals treated with TPA showed a dramatic decrease in plasma fibrinogen and factor VIII concentrations, but those in the Bat-PA treatment group showed only a slight decrease from control values. CONCLUSIONS: The results indicate that fibrinolytic bleeding after plasminogen activator infusion into rabbits did not correlate with the intensity of the plasma proteolytic state. If anything, Bat-PA usage was associated with a higher proportion of more protracted fibrinolytic bleeding episodes, despite the relatively mild lytic state in comparison with that induced by TPA.
BACKGROUND:Vampire bat salivary plasminogen activator (Bat-PA) has significantly greater fibrin specificity than any of the fibrinolytic agents currently in clinical use. This study tests the hypothesis that avoiding fibrinogen depletion may protect against the hemorrhage induced by plasminogen activator treatment. METHODS AND RESULTS:Bat-PA was compared with tissue-type plasminogen activator (TPA) in a randomized, prospective, and blinded study using a rabbit ear puncture model of fibrinolytic bleeding. The two agents were used at equimolar dosages (42 nmol/kg) that yielded similar thrombolytic efficacies in a rabbit femoral artery thrombosis model. Both Bat-PA and TPA prolong primary bleeding to double the baseline values, from between 2.1 and 2.3 minutes to between 4.8 and 5.2 minutes. Rebleeding from hemostatically stable sites during the 3-hour observation period occurred equally often with Bat-PA and TPA, 31% from preinjection sites and 23% to 25% from postinjection sites. The lag time between the time of plasminogen activator injection and the onset of rebleeding was likewise the same for both agents, most occurring at 41 to 57 minutes. However, a greater number of prolonged primary or rebleeding occurrences continued for longer than 10 minutes (63% versus 36%) or longer than 30 minutes (30% versus 10%) after Bat-PA than TPA injection. Animals treated with TPA showed a dramatic decrease in plasma fibrinogen and factor VIII concentrations, but those in the Bat-PA treatment group showed only a slight decrease from control values. CONCLUSIONS: The results indicate that fibrinolytic bleeding after plasminogen activator infusion into rabbits did not correlate with the intensity of the plasma proteolytic state. If anything, Bat-PA usage was associated with a higher proportion of more protracted fibrinolytic bleeding episodes, despite the relatively mild lytic state in comparison with that induced by TPA.