Basic principles in thrombolysis: regulatory role of plasminogen.

During thrombolytic therapy, patients are treated with a plasminogen activator in order to stimulate the fibrinolytic system by converting the precursor plasminogen into the active enzyme plasmin. The fibrinolytic process can be divided into two phases. In the first phase, plasminogen binds to intact fibrin and initial fibrinolysis takes place. As a result, carboxyterminal lysine residues are generated, which represent new binding sites for plasminogen. In the second phase, plasminogen binds to these sites and fibrinolysis is accelerated because the local plasminogen concentration is strongly enhanced and because this plasminogen has a higher reactivity. For instance, both single-chain urokinase-type plasminogen activator (scu-PA) and staphylokinase have a high preference for this type of plasminogen, which explains their fibrin-selective action. A recently discovered thrombin-activatable fibrinolysis inhibitor (TAFI) eliminates carboxyterminal lysine residues from partially degraded fibrin and, thus, inhibits the second phase of fibrinolysis. These mechanisms show that plasminogen plays an important regulatory role in fibrinolysis and thrombolysis.