Tissue plasminogen activator is an enzyme that catalyzes the conversion of plasminogen to plasmin for clot breakdown. Therefore, it is approved for the treatment of embolic or thrombotic stroke, but use is contraindicated in hemorrhagic stroke. Several clinical trials have shown that intravenous thrombolytic therapy for ischemic stroke using tissue plasminogen activator within a "therapeutic window" treatment time of 3 hours is the best available approach to improve the clinical outcome safely. Tissue plasminogen activator has been administered effectively as late as 6 hours after the onset of stroke. There is still some concern about hemorrhagic complications.
• Tissue plasminogen activator is approved for thrombolytic therapy of acute ischemic stroke.
• Two decades of clinical use, including numerous clinical trials, show that it is the first-line treatment of acute ischemic stroke due to thrombosis or embolism.
• A recognized complication is intracerebral hemorrhage.
Historical note and terminology
Although the potential of thrombolytic agents for treating ischemic stroke was recognized in the 1950s, further development was held back because of the fear of high risk of death from intracranial hemorrhage. Streptokinase and urokinase have been commercially available since 1978 and are referred to as first generation thrombolytics. Thrombolytic therapy in acute stroke patients has been studied extensively during the past 10 years, and second generation thrombolytics have evolved. One of these second generation thrombolytics is tissue plasminogen activator (tPA), which received approval from the United States Food and Drug Administration in 1996 and has become part of emergency care of patients with stroke. The approval of tissue plasminogen activator for treatment of patients with ischemic stroke in the United States marked the first therapy proven to reverse or limit the effects of acute stroke. Alteplase is a tissue plasminogen activator produced by recombinant DNA technology.
North American perspectives on the use of tissue plasminogen activator in acute ischemic stroke are based on early pilot studies and phase 3 trials conducted by the National Institutes of Neurological Disorders and Stroke in the United States in 1995; these were the basis for Food and Drug Administration approval. Tissue plasminogen activator was approved for the treatment of patients within 3 hours of onset of stroke.
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