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The Relationship Between Recombinant Tissue Plasminogen Activator (rtPA) Beyond the 3 Hour Therapeutic Window and the Incidence of Intracerebral Hemorrhage in Acute Ischemic Stroke Patients

15 August 2009


INTRODUCTION: Thrombolytic treatment with recombinant tissue plasminogen activator (rtPA) is approved by the FDA and national institute of neurological disorders for use within 3 hours as standard therapeutic care after the onset of thrombolytic stroke. Therefore all patients who present later than 3 hours and those with an unknown time window are currently excluded from this treatment option. Thus only a small percentage of patients can benefit. It is essential to assess the safety and efficacy of tissue plasminogen activator, alteplase, when administered after the 3 hour onset for acute ischemic stroke patients to determine the increase in the incidence of intracerebral hemorrhage.

METHODS: The focus of this study is to review the current literature for the last 10 years on all studies pertaining to the safety and efficacy of tissue plasminogen activator “Alteplase” for thrombolytic stroke patients given beyond the 3 hour standard therapeutic care window. An extensive online article search via Ovid, Pubmed, and Up-to-date was performed as well as a review of articles from the years 1999-2009. Five articles were assessed along with several complimentary articles for use of thrombolysis treatment within and beyond the 3 hour time window after stroke onset.

RESULTS: A total of 5 articles; two controlled randomized trials, one prospective cohort studies, one parallel group trial, and one open label nonrandomized trial, qualified for this systematic review. Two studies indicate that Alteplase remains safe and improves clinical outcomes in patient with acute ischemic stroke. Another study concluded patient selection was more important than time of treatment for good outcome, a further study indicated that alteplase was non-significantly associated with lower infract growth and significantly associated with increased reperfusion in patients who had mismatch of diffusion weighted MRI vs. Perfusion weighted MRI, and the last study concluded that patients with large baseline of diffusion weighted MRI lesion volume who received early reperfusion appear to be at greater risk of symptomatic intracerebral hemorrhage after tPA therapy.

CONCLUSION: Based on this literature review, the use of intravenous thrombolysis alteplase improves functional outcomes at three months if given within three hours of the standard therapeutic window, however, alteplase can be given at 3 to 4.5 hours after ischemic stroke onset which will lead to moderate improvement, but it will increase the incidence of symptomatic intracerebral hemorrhage. In the last ten years several randomized trials have been published and studied on the use of thrombolysis for acute ischemic stroke beyond the three hour window, but there not enough studies to answer several questions like: which type of patients are most likely to be harmed, how accurate and precise is the benefit in these patients, what is the maximum dosage that can used in ischemic stroke patients after the three hour window without any harm to the patient? Additional randomized trials on this treatment are needed to improve the safety and efficacy of intravenous thrombolysis alteplase.


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