Use of anticoagulant therapy and cerebral microbleeds: a systematic review and meta-analysis

  • Yajun Cheng
  • Yanan Wang
  • Quhong Song
  • Ke Qiu
  • Ming LiuEmail author



Anticoagulant therapy increases the risk that cerebral microbleeds (CMBs) progress to intracerebral hemorrhage, but whether the therapy increases risk of CMB occurrence is unclear. We performed a systematic review and meta-analysis to investigate the potential association between anticoagulant use and CMB occurrence in stroke and stroke-free individuals.


We searched observational studies in PubMed, Ovid EMBASE, and Cochrane Library from their inception until September 2019. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) for the prevalence and incidence of CMBs in anticoagulant users relative to non-anticoagulant users.


Forty-seven studies with 25,245 participants were included. The pooled analysis showed that anticoagulant use was associated with CMB prevalence (OR 1.54, 95% CI 1.26–1.88). The association was observed in subgroups stratified by type of participants: stroke-free, OR 1.86, 95% CI 1.25–2.77; ischemic stroke/transient ischemic attack, OR 1.33, 95% CI 1.06–1.67; and intracerebral hemorrhage, OR 2.26, 95% CI 1.06–4.83. Anticoagulant use was associated with increased prevalence of strictly lobar CMBs (OR 1.68, 95% CI 1.22–2.32) but not deep/infratentorial CMBs. Warfarin was associated with increased CMB prevalence (OR 1.64, 95% CI 1.23–2.18), but novel oral anticoagulants were not. Anticoagulant users showed higher incidence of CMBs during long-term follow-up (OR 1.72, 95% CI 1.22–2.44).


Anticoagulant use is associated with higher prevalence and incidence of CMBs. This association appears to depend on location of CMBs and type of anticoagulants. More longitudinal investigations with adjustment for confounders are required to establish the causality.


Anticoagulants Cerebral microbleeds Intracerebral hemorrhage Prevalence Incidence Meta-analysis 



This study was supported by the National Key Research and Development Program, Ministry of Science and Technology of China (2016YFC1300500-505); Major International (Regional) Joint Research Project, National Natural Science Foundation of China (81620108009); Key Research and Development Program, Science &Technology Department of Sichuan Province (2017SZ0007); and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18009).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

The manuscript does not contain clinical studies or patient data.

Supplementary material

415_2019_9572_MOESM1_ESM.docx (1.7 mb)
Supplementary file1 (DOCX 1765 kb)


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Center of Cerebrovascular Disease, West China HospitalSichuan UniversityChengduChina
  2. 2.West China School of MedicineSichuan UniversityChengduChina

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