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Original Investigation
December 2015

Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study

Author Affiliations
  • 1Department of Neurology, Columbia University Medical Center, New York, New York
  • 2currently with the Department of Neurology, Brown University, Providence, Rhode Island
  • 3Department of Neurology, Cleveland Clinic Foundation, Cleveland, Ohio
  • 4Department of Neurology, Washington University in St Louis, St Louis, Missouri
  • 5Department of Neurology, University of Arkansas for Medical Sciences, Fayetteville
  • 6Department of Neurology, Tulane University, New Orleans, Louisiana
  • 7Department of Neurology, The University of Alabama at Birmingham, Birmingham
  • 8Department of Neurology, UCLA (University of California, Los Angeles), for the UCLA Acute Stroke Investigators, Los Angeles
  • 9Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia
  • 10Department of Neurology, University of Oklahoma, Norman
  • 11Department of Neurology, Massachusetts General Hospital, Boston
JAMA Neurol. 2015;72(12):1451-1457. doi:10.1001/jamaneurol.2015.2371

Importance  Treatments for symptomatic intracerebral hemorrhage (sICH) are based on expert opinion, with limited data available on efficacy.

Objective  To better understand the natural history of thrombolysis-related sICH, with a focus on the efficacy of various treatments used.

Design, Setting, and Participants  Multicenter retrospective study between January 1, 2009, and April 30, 2014, at 10 primary and comprehensive stroke centers across the United States. Participants were all patients with sICH, using the definition by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), which included a parenchymal hematoma type 2 and at least a 4-point increase in the National Institutes of Health Stroke Scale score.

Main Outcomes and Measures  The primary outcome was in-hospital mortality, and the secondary outcome was hematoma expansion, defined as a 33% increase in the hematoma volume on follow-up imaging.

Results  Of 3894 patients treated with intravenous recombinant tissue plasminogen activator (rtPA) within 4½ hours after symptom onset of ischemic stroke, 128 (3.3%) had sICH. The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes (range, 30-2572 minutes), and the median time from diagnosis to treatment of sICH was 112 minutes (range, 12-628 minutes). The in-hospital mortality rate was 52.3% (67 of 128), and 26.8% (22 of 82) had hematoma expansion. In the multivariable models, code status change to comfort measures after sICH diagnosis was the sole factor associated with increased in-hospital mortality (odds ratio, 3.6; 95% CI, 1.2-10.6). Severe hypofibrinogenemia (fibrinogen level, <150 mg/dL) was associated with hematoma expansion, occurring in 36.3% (8 of 22) of patients without hematoma expansion vs in 25.0% (15 of 60) of patients with hematoma expansion (P = .01), highlighting a role for cryoprecipitate in reversing rtPA coagulopathy.

Conclusions and Relevance  In this study, treatment of postthrombolysis sICH did not significantly reduce the likelihood of in-hospital mortality or hematoma expansion. Shortening the time to diagnosis and treatment may be a key variable in improving outcomes of patients with sICH.