Plasminogen acceleration of urokinase thrombolysis

A relative deficiency of plasminogen within the thrombus may be the rate limiting factor in clot lysis.

To investigate this hypothesis, we used an in vitro perfusion system and expanded polytetrafluoroethylene graft segments filled with radiolabeled human thrombus. Three groups of five perfusions were compared: (1) urokinase infusion (333 IU/min) into clots laced with buffer, (2) urokinase infusion (333 IU/min) into clots laced with plasminogen (44 CU), and (3) control, D5W infusion into clots laced with buffer. Two end points were measured over time: the amount of lysed thrombus and the flow through the graft.

Urokinase infusion resulted in augmented flow through the graft when compared with control (p < 0.05). Lacing with plasminogen resulted in more rapid restoration of flow when compared with urokinase infusion alone (p < 0.05). Similarly, the rate of clot dissolution was significantly greater in plasminogen-laced thrombi (p < 0.05) when compared with the control and urokinase groups. Embolization of particles of thrombus was uniformly observed in the urokinase group, resulting in a temporary decrease in flow through the thrombosed graft. This event characteristically occurred after 60 minutes of infusion but was never seen in the urokinase/plasminogen treatment group.

These results suggest that plasminogen supplementation of urokinase thrombolysis may result in significant clinical benefits with respect to the rate of clot lysis and the uniformity of clot dissolution with a lower likelihood of secondary embolization.