Intracerebral hemorrhage due to thrombolytic therapy

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By James S McKinney MD and Steven R Messe MD

As of late 2009, 26 randomized controlled clinical trials of a thrombolytic agent versus control in acute ischemic stroke have been completed on 7152 patients. Most of these trials tested intravenous thrombolysis up to 6 hours after symptom onset. Of the trials, 55% tested recombinant tissue plasminogen activator, while others studied urokinase, streptokinase, recombinant pro-urokinase, ancrod, or desmoteplase. Overall, the odds of symptomatic intracranial hemorrhage were increased 3-fold (odds ratio 3.49, 95% confidence interval 2.81 to 4.33) in patients who received thrombolysis. In spite of this, there was a significantly reduced chance of poor outcome (combined death and dependency) during follow-up in patients who received thrombolytic therapy. This review summarizes current knowledge on the incidence, risk factors, clinical presentation, and management of intracerebral hemorrhage resulting from thrombolytic therapy. Dr. James S. McKinney is Medical Director of the Robert Wood Johnson University Hospital Comprehensive Stroke Center and Assistant Professor of Neurology at the Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey. Dr. Steven R. Messé is Director of the Vascular Neurology Fellowship and Assistant Professor of Neurology at the University of Pennsylvania.

Key Points

  • Thrombolytic therapies provide an effective treatment for select patients with acute ischemic stroke; however, these therapies have a risk of intracerebral hemorrhage.
  • The myriad definitions of symptomatic intracerebral hemorrhage has caused variability in the reported risk of hemorrhage and associated risk factors.
  • The NINDS rtPA Stroke Study reported a 6.4% rate of symptomatic intracerebral hemorrhage after intravenous rtPA for stroke within 3 hours of symptom onset, and a rate of 5% to 6% has been reported in subsequent series of patients treated in clinical practice.
  • Severe stroke, early CT changes, and hyperglycemia or a history of diabetes have consistently been reported to be independent risk factors for post-thrombolysis intracerebral hemorrhage.