Locally delivered plasmin: why should it be superior to plasminogen activators for direct thrombolysis?

With advances in the field of thrombolytic therapy, whereby clots are routinely treated locally via a catheter, traditional systemic thrombolytics such as plasminogen activators might not be the best drugs for this task. Plasmin represents a new class of thrombolytic agents that exhibit direct fibrinolytic activity, without the need for either plasminogen or a plasminogen activator. In contrast to plasminogen activators, this independence from plasminogen allows plasmin to efficiently dissolve long, retracted blood clots that are inherently deficient in plasminogen. Preclinical safety studies in rabbits demonstrate that plasmin, in contrast to tissue-type plasminogen activator, does not cause re-bleeding from preformed hemostatic plugs. These results predict that plasmin will prove to be both superior to, and safer than, plasminogen activators in the dissolution of long, retracted blood clots in humans.