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Risk of intracranial hemorrhage associated with therapeutic anticoagulation for venous thromboembolism in cancer patients: a systematic review and meta-analysis

Abstract

Intracranial hemorrhage (ICH) in cancer patients can result from tumor bleeding and from antitumor and anticoagulation therapy. The effect of anticoagulation on the incidence of ICH in cancer patients has not been quantified. Our objective was to determine the risk of intracranial hemorrhage associated with anticoagulation therapy for cancer-associated venous thromboembolism (VTE). Systematic review and meta-analysis of studies assessing the safety of anticoagulation therapy in patients with cancer-associated VTE. The primary endpoint of interest was the incidence of ICH and secondary outcomes included all major bleeding, and the time to ICH and major bleeding. After identifying 595 studies, five studies and 2089 patients were included in the analyses. We found that the relative risk (RR) for ICH was 0.494, 95 % CI (0.105–2.331) when low molecular weight heparin (LMWH) with vitamin K antagonist (VKA) anticoagulants were compared. No statistically significant differences in risk were measured. The risk of major bleeding using any type of anticoagulation therapy in patients with cancer-associated VTE was RR 0.853, 95 % CI (0.549, 1.327). After meta-analytic review of data published through August 2015, we conclude that therapeutic anticoagulation with LMWH given ≤6 months does not increase the risk of ICH in cancer patients compared to VKA. The risk of ICH in cancer patients is also similar to that of non-cancer patients. Available data were insufficient to determine if the ICH risk increase changes when the duration of anticoagulation is >6 months.

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Acknowledgments

The authors thank Dr. Michael H. Kroll for his critical reading of the manuscript.

Funding

The authors declare that funding source had no involvement. The funders of the original studies had no role in the study design, management, data analysis, and data interpretation.

Author contributions

C.M.R. conceived the study, performed the literature search, data extraction and analysis, quality assessment and contributed writing the manuscript; T.H.O. contributed with data analysis and writing the manuscript; H.A.G. conducted the literature search, designed and performed data extraction and analysis, quality assessment, and contributed writing the manuscript; all authors provided input to the study design and critical review and revision of the manuscript.

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Correspondence to Cristhiam M. Rojas-Hernandez.

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Conflict of interest

Dr. Rojas-Hernandez has received financial support for clinical research from Daichii Sankyo, which does not have relationship with the work presented in this manuscript. Dr. Oo has received financial support for clinical research from Daichii Sankyo, which does not have relationship with the work presented in this manuscript. Dr. García-Perdomo has no conflicts of interest to report.

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Rojas-Hernandez, C.M., Oo, T.H. & García-Perdomo, H.A. Risk of intracranial hemorrhage associated with therapeutic anticoagulation for venous thromboembolism in cancer patients: a systematic review and meta-analysis. J Thromb Thrombolysis 43, 233–240 (2017). https://doi.org/10.1007/s11239-016-1434-4

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Keywords

  • Intracranial hemorrhage
  • Anticoagulation
  • Cancer
  • Venous thromboembolism