Fibrinolytic dynamics following accelerated thrombolysis of tissue-type plasminogen activator combined with urokinase

The combination of tissue type plasminogen activator (t-PA) and urokinase (UK) for thrombolysis decreases the incidence of reocclusion rate compared with the t-PA alone and increases the patency rate, although their mechanisms have not been elucidated. In this report, the t-PA level in blood and fibrinolytic dynamics after the combination use of t-PA and UK was studied. Femoral artery thrombosis models of twenty beagle dogs (mean body weight 11.8 ± 2.4 kg) were randomly divided into two groups; t-PA alone (0.75 mg/kg) and t-PA (0.75 mg/kg) with UK (60,000 units). Each group was divided into two subgroups according to the administration period, 5 min (accelerated) and 60 min. The levels of fibrinogen, plasminogen, tPA-PAI 1 complex, α₂-plasmin inhibitor complex, and t-PA were comparatively studied for 24 hours in each group. In the combination thrombolysis groups, the levels of fibrinogen and plasminogen were decreased at least for 3 hours (p<0.05), and the levels of tPA-PAI 1 complex and α₂-plasmin inhibitor complex were sustained at significant levels (p<0.05). In the accelerated thrombolysis group, the t-PA blood level reached its peak earlier and decreased rapidly; furthermore, the accelerated combination thrombolysis group had a significantly higher peak of t-PA blood level than the t-PA alone group (60 min; 538.3 ± 128.5 ng/ml vs. 347.0 ± 41.3 ng/ml, p<0.05) (5 min; 2,537.5 ± 780.9 ng/ml vs. 917.3 ± 79.2 ng/ml, p<0.05) and had an appropriate long-term effect on fibrinolytic dynamics. In conclusion, it was suggested that accelerated combination thrombolysis decreases the reocclusion rate by its appropriate long-term effect on fibrinolytic dynamics and increases the patency rate by the elevation of t-PA peak blood level.