REVIEW – July 2005

Thrombolytic therapy for acute ischemic stroke

Authors: Janika Kõrv, Mai Roose, Riina Vibo

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Abstract

The main goal of thrombolysis is to restore the bloodflow in the ischemic area of the brain and to stop the neuronal ischemic cascade damaging the neurons and to prevent their premature death. All the thrombolytic agents are the activators of plasminogen, which convert the proenzyme plasminogen to plasmin. The plasmin destroys the most important component of the thrombus – the fibrin an therefore causing the whole thrombus to dissolve. The thrombolytic agents studied include streptokinase, urokinase, recombinant pro-urokinase and recombinant tissue plasminogen activator (rt-PA). The three big clinical studies of streptokinase in acute ischemic stroke were disrupted due to negative results: the risk of intraparenhymal hemorrhages and death was signifficantly higher in treatment group vs placebo, the functional recovery was not improved with therapy. The results from clinical studies with urokinase were not so negative, but they were not finished after all. Only the rt-PA, synthesised in 1980s, has reached the clinical practice and is used for the thrombolytic treatment of acute ischemic stroke. Four large comparable studies with alteplase have been conducted. The results have been promising and in 1996, the US Food and Drug Administration approved the use of alteplase in the treatment of acute ischemic stroke in selected patients within 3 hours from the onset of symptoms. The administration of the drug is relatively easy, but the risk of serious side effects demands the procedure to be carried through in specialised centers by trained personel.