A novel role for tissue-type plasminogen activator: prevention of thromboembolic occlusion.

Activation of plasminogen by agents such as tissue-type plasminogen activator (tPA), yields plasmin, lyses fibrin, and thereby restores flow to blood vessels occluded by thrombi. Because tPA binds to fibrin, as does plasminogen, at low doses, tPA-mediated generation of plasmin is localized, rendering tPA clot selective. This result, plus its short half-life (4.5 minutes), led to the hope that its use would not only enhance coronary and cerebral thrombolysis but also reduce the risk of bleeding, including intracranial hemorrhage.1 At high conventionally used doses, clot selectivity is incomplete. Perhaps that is why treatment with tPA compared with a non–clot-selective agent, streptokinase, reduced mortality in patients with ST-elevation myocardial infarction but did not diminish the incidence of intracranial hemorrhage.2