Cerebral Microbleeds and the Safety of Anticoagulation in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis

OBJECTIVES: The objective of this study was to investigate the safety of anticoagulation in ischemic stroke (IS) patients with cerebral microbleeds (CMBs). METHODS: PubMed, Web of Science, Elsevier Clinical Key, Google Scholar, and Cochrane Library from 1996 to July 2018 were searched to identify relevant studies that included IS patients, underwent T2*-weighted gradient recalled echo, or susceptibility-weighted imaging for detection CMBs and used anticoagulants during follow-up. Primary outcome of interest was intracerebral hemorrhage (ICH). Secondary outcomes were hemorrhage transformation, IS, total mortality, and new developed CMBs. We critically appraised studies and conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. RESULTS: We included 7 observational studies. Cerebral microbleeds were associated with a significantly elevated risk of anticoagulation-related ICH (odds ratio, 4.01; 95% confidence interval, 1.82-8.81; P = 0.001). It was significant for warfarin (odds ratio, 8.02; 95% confidence interval, 1.51-42.62; P = 0.015). New developed CMBs in patients on warfarin treatment were associated with baseline CMBs, and the appearance of hemorrhagic transformation did not have a significant relationship with baseline CMBs. CONCLUSIONS: The presence of CMBs increases the risk of ICH during anticoagulant treatment (especially warfarin) in IS patients. Further studies with larger numbers of patients are needed to confirm our conclusions.