Article Text

Download PDFPDF
Original research
Intracerebral haemorrhage in patients with brain metastases receiving therapeutic anticoagulation
  1. Peter Wood1,
  2. Giovanni Boyer2,
  3. Elie Mehanna3,
  4. Daniel Cagney2,
  5. Nayan Lamba3,
  6. Paul Catalano4,5,
  7. Jean M Connors6,
  8. Liangge Hsu7,
  9. Mallika Mendu8,
  10. Shyam Tanguturi2,
  11. Brian Alexander2,
  12. Daphne Haas-Kogan2,
  13. Ayal Aizer2
  1. 1Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
  2. 2Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA
  3. 3Harvard Radiation Oncology Program, Departments of Radiation Oncology, Brigham and Women's Hospital / Massachusetts General Hospital, Boston, MA, USA
  4. 4Department of Biostatistics, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
  5. 5Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  6. 6Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  7. 7Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  8. 8Department of Quality and Safety, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Ayal Aizer, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; aaaizer{at}


Background Venous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added risk of ICH in patients with brain metastases receiving therapeutic anticoagulation.

Methods We performed a matched, retrospective cohort study of 291 patients (100 receiving therapeutic anticoagulation vs 191 controls) with brain metastases managed at Brigham and Women’s Hospital/Dana-Farber Cancer Institute between 1998 and 2015. For each patient, all MRI studies of the brain were reviewed to identify ICH. Propensity score matching and multivariable Cox regression were used to mitigate confounding.

Results The risk of ICH was comparable in patients receiving anticoagulation versus controls preanticoagulation. Postanticoagulation, we observed significant or borderline-significant associations between anticoagulation and development of any ICH (HR 1.31, 95% CI 0.96 to 1.79, p=0.09), ICH as identified by gradient echo/susceptibility-weighted imaging (HR 1.46, 95% CI 1.06 to 2.01, p=0.02), symptomatic ICH (HR 1.80, 95% CI 1.01 to 3.22, p=0.05), extralesional ICH (HR 5.82, 95% CI 1.56 to 21.7, p=0.009) and fatal ICH (HR 5.68, 95% CI 0.60 to 54.2, p=0.13). Anticoagulation was associated with differentially higher ICH risk in patients with prior ICH versus no prior ICH (HR 2.20 vs 0.68, respectively, p interaction <0.001) and symptomatic ICH risk in melanoma versus other primary malignancies (HR 6.46 vs 1.36, respectively, p interaction=0.02).

Conclusions Anticoagulation is associated with clinically significant ICH in patients with brain metastases, especially those with melanoma or prior ICH. The indication for anticoagulation and risk of intracerebral bleeding should be considered on an individual basis among such patients.

Data availability statement

Data may be obtained from a third party and are not publicly available.

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.

Data availability statement

Data may be obtained from a third party and are not publicly available.

View Full Text


  • Correction notice This article has been corrected since it first published. The provenance and peer review statement has been included.

  • Contributors The study was conceived and designed by PW, GB, PC, JMC and AA. PW, GB, DC and AA collected data for the study. EM, DC, NL, LH, MM, ST, BA and DH-K contributed to the scientific design and conduct of the study. PC oversaw the biostatistical approach to the study; the analysis was reviewed by all other authors. PW, GB, PC and AA also wrote the first draft of the manuscript; all other authors reviewed and edited the manuscript. AA is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests AA reports research funding from Varian Medical Systems.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Linked Articles