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Tissue plasminogen activator activates plasminogen directly, with a half life shorter than that of streptokinase. It is a naturally occurring enzyme produced by a number of tissues, including vascular endothelial cells.
There are binding sites in the TPA molecule that are available for fibrin. This allows the TPA molecule to attach to a formed thrombus and lyse it. In the body this process can occur without extensive activation of plasminogen in the general circulation. However if used at current clinical dosages, some systemic plasminogen activation can occur.
The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries - GUSTO - trial showed the benefit of 'accelerated' TPA plus intravenous heparin over the use of other regimes:
In the GUSTO study all the patients were given 160-325mg of aspirin daily.