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Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis


  • Conflict of interest: None declared.
  • Funding: Dr Benavente is funded by NIH grant no. 2 U01 NS38529-04A1.

Correspondence: Ashkan Shoamanesh, Brain Research Centre, UBC Hospital, 2211 Wesbrook Mall, Room 5192, Vancouver, BC, Canada V6T 2B5.



It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I2 = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I2 = 0%] reaching borderline significance (P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage (P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of cerebral microbleed presence.