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  • Updated 07.23.2023
  • Released 07.16.1996
  • Expires For CME 07.23.2026

Intracerebral hemorrhage due to thrombolytic therapy



Treatment of acute ischemic stroke with recombinant tissue plasminogen activator (rtPA or t-PA) and endovascular intervention leads to improved outcome, as demonstrated in several randomized clinical trials. A small percentage of stroke patients receiving thrombolysis experience symptomatic hemorrhagic conversion of the ischemic stroke, leading to disability or death. In this article, the author reviews the clinical presentation, risk factors, and management of thrombolysis-induced hemorrhagic transformation of cerebral ischemic stroke, the most dreaded complication of acute stroke therapy.

Key points

• Thrombolysis is an effective treatment for select patients with acute ischemic stroke; the most feared risk of thrombolysis is intracerebral hemorrhage.

• Multiple definitions of symptomatic intracerebral hemorrhage have caused variability in the reported risk and associated risk factors.

• The 1995 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.

• As of 2008, the American Stroke Association recommends intravenous rtPA for patients presenting within 4.5 hours of stroke symptom onset with a few additional accepted exclusion criteria resulting in improved clinical outcomes and a 2.4% risk of symptomatic hemorrhagic complications.

• Addition of endovascular thrombectomy to IV-tPA is superior to IV-tPA alone in appropriately selected patients with acute ischemic stroke due to occlusion of a large intracranial artery, and combination therapy carries a similar rate of hemorrhagic conversion.

• Large stroke, early CT changes of ischemia, hyperglycemia, or a history of diabetes have been associated with post-thrombolysis intracerebral hemorrhage.

Historical note and terminology

Sussman and Fitch were the first to report thrombolysis for the treatment of acute ischemic stroke (96). Before the advent of CT that allows exclusion of hemorrhagic stroke, thrombolysis was administered several hours or days after stroke onset. The high rates of intracranial hemorrhage and death led to the cessation of the clinical use of thrombolysis (08).

In the National Institute of Neurological Disorders and Stroke (NINDS) trial, intravenous recombinant tissue plasminogen activator (IV-rtPA) administered within 3 hours of ischemic stroke onset resulted in a 30% likelihood of very good outcome at 3 months compared to placebo, despite a 6.4% risk of symptomatic intracerebral hemorrhage (sICH) (76). The United States Food and Drug Administration (FDA) approved IV-rtPA for selected patients with ischemic stroke within 3 hours from onset. Favorable outcomes with an acceptable hemorrhagic conversion rate of 2.4% led to the ASA/AHA guideline recommendations for rtPA administration in the 3.0- to 4.5-hour post-stroke symptom-onset window (42); however, this indication has not yet been approved by the FDA (14). Finally, several 2015 published controlled trials demonstrated reduced disability in patients receiving endovascular therapy combined with IV-tPA for ischemic strokes due to large vessel occlusion when compared to IV-tPA alone, without additional risk of sICH (82).

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