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Symptomatic Intracerebral Hemorrhage in Acute Ischemic Stroke After Thrombolysis With Intravenous Recombinant Tissue Plasminogen Activator:  A Review of Natural History and Treatment

Shadi Yaghi, MD1; Andrew Eisenberger, MD2; Joshua Z. Willey, MD, MS1
[+] Author Affiliations
1Division of Stroke and Cerebrovascular Diseases, Department of Neurology, Columbia University, New York, New York
2Division of Hematology and Oncology, Department of Medicine, Columbia University, New York, New York
JAMA Neurol. 2014;71(9):1181-1185. doi:10.1001/jamaneurol.2014.1210.
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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.

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Figure.
Coagulation and Fibrinolytic Pathways Showing the Mode of Action of Symptomatic Intracerebral Hemorrhage Treatment

FFP indicates fresh frozen plasma; IV, intravenous; PCC, prothrombin complex concentrate; rtPA, recombinant tissue plasminogen activator; +, activation; and −, inhibition. Treatments are indicated with boldface type.

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