Possible mechanism of vascular reocclusion after initially successful thrombolysis with recombinant tissue-type...

We studied the effects of urokinase (UK), pro-urokinase (pro-UK), and recombinant tissue-type plasminogen activator (rt-PA) on platelet aggregation and the production of thromboxane A2 (TXA2) in vitro. Both UK and pro-UK inhibited the platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen, or thrombin in a concentration-dependent manner. In contrast, although a low dose of rt-PA (5 to 10 x 10(4) U/ml) blunted platelet aggregability, a high dose (40 to 60 x 10(4) U/ml) led to platelet hyperaggregation. UK and pro-UK markedly inhibited TXA2 synthesis during ADP-induced platelet aggregation. Despite the significant reduction of TXA2 synthesis by 10 x 10(4) U/ml rt-PA, a concentration of 60 x 10(4) U/ml rt-PA had no effect on synthesis. These results indicate that UK and pro-UK each inhibit platelet function, but a high concentration of rt-PA enhances platelet aggregability. This finding may at least in part contribute to the high incidence of reocclusion after initially successful thrombolysis with rt-PA.