Article Text

Download PDFPDF
Research paper
Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study
  1. Yannie Soo1,
  2. Jill M Abrigo2,
  3. Kam Tat Leung1,
  4. Suk Fung Tsang1,
  5. Hing Lung Ip1,
  6. Sze Ho Ma1,
  7. Karen Ma1,
  8. Wing Chi Fong3,
  9. Siu Hung Li4,
  10. Richard Li5,
  11. Ping Wing Ng6,
  12. Kwok Kui Wong7,
  13. Wenyan Liu1,
  14. Bonnie Y K Lam1,
  15. Ka Sing Lawrence Wong1,
  16. Vincent Mok1,
  17. Winnie Chiu Wing Chu2,
  18. Thomas W Leung1
  19. On behalf of the IPAAC study group
    1. 1 Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
    2. 2 Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
    3. 3 Department of Medicine, Queen Elizabeth Hospital, King's Park, Hong Kong
    4. 4 Department of Medicine, Northern District Hospital, Sheung Shui, Hong Kong
    5. 5 Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
    6. 6 Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong
    7. 7 Department of Medicine, Yan Chai Hospital, Tsuen Wan, Hong Kong
    1. Correspondence to Professor Thomas W Leung, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong; drtleung{at}


    Background and purpose Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs.

    Methods In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs.

    Results A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH.

    Conclusions In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

    • cerebral microbleeds
    • intracerebral hemorrhage
    • warfarin
    • atrial fibrillation
    • Chinese

    Statistics from

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


    • Collaborators Anne Chan, Howan Leung, Florence Fan, Lisa Au, Cyrus Cheng (Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong); Joshua Fok (Department of Medicine, Yan Chai Hospital); Kwok Kwong Lau (Department of Medicine, Princess Margaret Hospital); Jonas Yeung (Department of Medicine, Alice Ho Miu Ling Nethersole Hospital).

    • Contributors YS conceptualised the project, wrote the protocol, performed literature review, reviewed radiological images, collected and analysed data, and prepared the manuscript. JMA and WCWC provided radiological support. KTL and SFT designed the data extraction form, collected data and performed statistical analyses. HLI, SHM, KM, WCF, SHL, RL, PWN and KKW assisted in patient recruitment, collected data and reviewed the manuscript. WL and BYKL rated white matter score and reviewed the manuscript. KSLW, VM and TWL conceptualised the project, and reviewed the protocol and manuscript.

    • Funding The IPAAC-Warfarin study was funded by the Health and Medical Research Fund of Food and Health Bureau, and partially supported by Kwok Tak Seng Center for Stroke Research and Intervention.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval The study has been approved by Clinical Research Ethics Committee in New Territories East, Kowloon Central, Kowloon East, Kowloon West and Hong Kong East Clusters.

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