title: Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.
abstract: OBJECTIVE
  Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature.
  
  
  METHODS
  We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses.
  
  
  RESULTS
  We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables.
  
  
  CONCLUSIONS
  Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.
authors.affiliation: Division of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK. william.whiteley@ed.ac.uk
authors.forename: William N
authors.initials: WN
authors.lastname: Whiteley
authors.forename: Karsten Bruins
authors.initials: KB
authors.lastname: Slot
authors.forename: Peter
authors.initials: P
authors.lastname: Fernandes
authors.forename: Peter
authors.initials: P
authors.lastname: Sandercock
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator