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Cerebral Microbleeds and the Safety of Anticoagulation in Ischemic Stroke Patients

A Systematic Review and Meta-Analysis

Liang, Yifan, MD*; Song, Quhong, MD; Jiao, Yang, MD; Lin, Jueying, MD§; Qu, Huiling, MD, PhD; Zhao, Shanshan, MD, PhD*; Xu, Junjie, MD, PhD; Zhao, Chuansheng, MD, PhD*; Zhao, Mei, MD, PhD#

doi: 10.1097/WNF.0000000000000306
Review Articles

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.

*Department of Neurology, The First Hospital of China Medical University, Shenyang;

Department of Neurology, West China Hospital of Sichuan University, Chengdu;

Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian;

§Emergency Department, Zhongshan Hospital Xiamen University, Xiamen;

Department of Neurology, The People's Hospital of Liaoning Province;

Department of Laboratory Medicine, The First Hospital of China Medical University; and

#Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, China.

Address correspondence and reprint requests to Mei Zhao, MD, PhD, Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning, China; zhaom1@sj-hospital.org; or Chuansheng Zhao, MD, PhD, Department of Neurology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China; E-mail: cszhao@mail.cmu.edu.cn

Yifan Liang and Quhong Song contributed to this work equally.

Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare.

This work was supported by National Natural Science Foundation of China (no. 81372104, C.Z.), the Shenyang Population and Health Technical Critical Special Project (no. F16-206-9-01, C.Z.), and the Program of the Distinguished Professor of Liaoning Province, Neurology (C.Z.).

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