Symptomatic intracerebral hemorrhage in acute ischemic stroke after thrombolysis with intravenous recombinant tissue plasminogen activator: a review of natural history and treatment

JAMA Neurol. 2014 Sep;71(9):1181-5. doi: 10.1001/jamaneurol.2014.1210.


Importance: Intravenous thrombolysis remains the mainstay treatment for acute ischemic stroke. One of the most feared complications of the treatment is thrombolysis-related symptomatic intracerebral hemorrhage (sICH), which occurs in nearly 6% of patients and carries close to 50% mortality. The treatment options for sICH are based on small case series and expert opinion, and the efficacy of recommended treatments is not well known.

Objective: To provide an overview on the rationale and mechanism of action of potential treatments for sICH that may reverse the coagulopathy before hematoma expansion occurs.

Evidence review: Evidence-based peer-reviewed articles, including randomized trials, case series and reports, and retrospective reviews, were identified in a PubMed search on the mechanism of action of intravenous recombinant tissue plasminogen activator and the rationale of various potential treatments using the coagulation cascade as a model. The search encompassed articles published from January 1, 1990, through February 28, 2014.

Findings: The current treatments may not be sufficient to reverse coagulopathy early enough to prevent hematoma expansion and improve the outcome of thrombolysis-related hemorrhage.

Conclusions and relevance: Given the mechanism of action of intravenous recombinant tissue plasminogen activator, clinical studies could include agents with a fast onset of action, such as prothrombin complex concentrate, recombinant factor VIIa, and ε-aminocaproic acid, as potential therapeutic options.

Publication types

  • Review

MeSH terms

  • Brain Ischemia / drug therapy*
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / therapy*
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects*
  • Humans
  • Stroke / drug therapy*
  • Thrombolytic Therapy / adverse effects*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / adverse effects*


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator