Alteplase (recombinant tissue plasminogen activator) was developed with the aim of providing a fibrin-clot-specific thrombolytic agent that would be less likely to induce systemic fibrinolysis or fibrinogenolysis. It is a purified fibrinolytic glycoprotein of 527 amino acids, synthesized using the complementary DNA for natural human tissue-type plasminogen activator. Alteplase is cleared rapidly from circulating plasma, mainly by the liver, with approximately 80 per cent cleared within 10 min (slightly slower in people with thrombosis). It binds to fibrin in a thrombus and converts the bound plasminogen to plasmin, initiating local fibrinolysis with minimal systemic effects. There is a decrease of 20 to 30 per cent in circulating fibrinogen and associated decreases in plasminogen and a 2-antiplasmin. Alteplase has proved slightly more effective at reopening thrombosed vessels, particularly if administration has been delayed for more than 3 h after the onset of occlusion. This benefit appears to be offset by a higher reocclusion rate if heparin does not produce adequate prolongation of activated partial thromboplastin time. The incidence of cerebral hemorrhage is also greater with tissue plasminogen activator than with streptokinase.

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