J Neurol Neurosurg Psychiatry 81:679-684 doi:10.1136/jnnp.2009.198994
  • Research paper

Brain microbleeds as a potential risk factor for antiplatelet-related intracerebral haemorrhage: hospital-based, case–control study

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  1. D J Werring1
  1. 1Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
  2. 2Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
  3. 3Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK
  1. Correspondence to Dr David J Werring, Stroke Research Group, National Hospital for Neurology and Neurosurgery Box 6, Queen Square, London WC1 N 3BG, UK; d.werring{at}
  1. Contributors SMG was responsible for the data acquisition, analyses, interpretation and writing of the manuscript. DJW and SMG contributed to the conception and design of the study. DJW also contributed to the data analysis, interpretation and review of the manuscript and supervised the whole project. HRJ helped with the review of the manuscript. TAY provided useful feedback on the manuscript. CK, statistician at the London School of Hygiene and Tropical Medicine, was responsible for the statistics. All authors revised and approved the final version of the manuscript.

  • Received 30 October 2009
  • Revised 23 December 2009
  • Accepted 15 January 2010


Background Intracerebral haemorrhage (ICH) is an uncommon but devastating complication of regular antiplatelet use: identifying high-risk patients before treatment could potentially reduce this hazard. Brain microbleeds on gradient-recalled echo (GRE) T2*-weighted MRI are considered a biomarker for bleeding-prone small-vessel diseases. The authors hypothesised that microbleeds are a risk factor for antiplatelet-related ICH, and investigated this in a hospital-based matched case–control study.

Methods Cases of spontaneous ICH were ascertained, using overlapping methods, from a prospective database of 1017 consecutive unselected patients referred to our stroke unit and associated clinics. For each case of antiplatelet-related ICH, two controls matched for age, sex and hypertension without history of ICH on antiplatelet therapy were selected. Microbleeds were identified by a trained observer blinded to clinical details.

Results Microbleeds were more frequent in antiplatelet users with ICH than in matched antiplatelet users without ICH (13/16 (81%) vs 6/32 (19%), p=0.004) and patients with non-antiplatelet-related ICH (13/16 (81%) vs 15/33 (45%), p=0.03). The frequency of lobar microbleeds was 11/16 (69%) in antiplatelet-related ICH versus 11/33 (33%) in non antiplatelet-related ICH (p=0.032). Microbleeds were more numerous in antiplatelet users with ICH compared with controls (p=0.016). The number of microbleeds was associated with the risk of antiplatelet-related ICH (adjusted OR 1.33 per additional microbleed, 95% CI 1.06 to 1.66, p=0.013).

Conclusions Brain microbleeds are associated with antiplatelet-related ICH. In patients with a large number of lobar microbleeds, the risk of ICH could outweigh the benefits of antiplatelet therapy. Larger prospective studies to investigate the prognostic significance of microbleeds in regular antiplatelet users are warranted.


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  • Funding SMG receives research support from the Stroke Association. HRJ has received research support from the Samantha Dickson Brain Tumour Trust and the Brain Research Trust. Professor Brown receives support from the Reta Lila Weston Trust for Medical Research (supports him as Chair in Stroke Medicine). DJW receives research support from the Department of Health/Higher Education Funding Council for England (Clinical Senior Lectureship Award) and the Stroke Association. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  • Competing interests HRJ serves as a consultant to Biogen Idec and GlaxoSmithKline. TAY served on a scientific advisory board for UCB and serves on the editorial board of European Radiology. MMB serves as a Section Editor for Stroke; serves as a consultant to Pfizer Inc. and AGA Medical Corporation, and serves on a Data and Ethics Monitoring Committee for Bayer Schering Pharma.

  • Ethics approval Ethics approval was provided by the Joint Institute of Neurology and National Hospital for Neurology and Neurosurgery Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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