Fig. 1.

A general principle of thrombolysis. Well-characterized plasminogen activators (tissue plasminogen activator, urokinase, desmoteplase, streptokinase, staphylokinase) show a unifying principle of activating plasminogen into the active form plasmin. If plasmin is bound to the surface of a fibrin clot, it digests selectively only fibrin to form soluble fibrin degradation products. This process cannot be inhibited by α₂-antiplasmin or α₂-macroglobulin because the recognition site of plasmin is sterically hindered by bound fibrin. If plasmin is generated in circulating blood, it can digest fibrinogen and factor VIII instead of fibrin. This process is rapidly inhibited by α₂-antiplasmin or α₂-macroglobulin. Fibrinogenolysis and subsequent plasminemia caused by inhibition often lead to extensive bleeding complications. As a consequence, only plasminogen activator highly selective towards fibrin-bound plasminogen can be effective in the treatment of cardiovascular diseases.