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Systemic coagulation is activated in patients with meningioma and glioblastoma

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Abstract

Purpose

Up to 30% of patients with glioblastoma (GBM) develop venous thromboembolism (VTE) over the course of the disease. Although not as high, the risk for VTE is also increased in patients with meningioma. Direct measurement of peak thrombin generation (TG) allows quantitative assessment of systemic coagulation activation in patients with GBM and meningioma. Our aim was to determine the extent of systemic coagulation activation induced by brain tumors, to measure the shift between pre- and post-operative peak TG in patients with GBM, and to assess the relationship between pre-surgical peak TG and pre-operative brain tumor volume on imaging.

Methods

Pre- and post-surgical plasma samples were obtained from successive patients with GBM and once from patients with meningioma and healthy age- and sex-matched blood donor controls. TG was measured using the calibrated automated thrombogram (CAT) assay, and tumor volumes were measured in pre-surgical MRI scans.

Results

Pre-surgical peak TG was higher in patients with GBM than in controls (288.6 ± 54.1 nM vs 187.1 ± 41.7 nM, respectively, P < 0.001), and, in the nine patients with GBM and paired data available, peak TG was significantly reduced after surgery (323 ± 38 nM vs 265 ± 52 nM, respectively, P = 0.007). Similarly, subjects with meningioma demonstrated higher peak TG compared to controls (242.2 ± 54.9 nM vs 177.7 ± 57.0 nM, respectively, P < 0.001). There was no association between peak TG and pre-operative tumor volume or overall survival.

Conclusion

Our results indicate that systemic coagulation activation occurs with both meningioma and GBM, but to a greater degree in the latter. Preoperative peak TG did not correlate with tumor volume, but removal of GBM caused a significant decrease in coagulation activation.

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Acknowledgements

This study was supported by grants from the Northern New England Clinical Oncology Society (NNECOS), the Brain Tumor Research Fund at Dartmouth-Hitchcock Medical Center, and by the Imaging Sciences Group of the Dartmouth Clinical and Translational Science Institute, under award number UL1TR001086 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the funding agencies.

Funding

This study was supported by grants from the Northern New England Clinical Oncology Society (NNECOS), the Brain Tumor Research Fund at Dartmouth-Hitchcock Medical Center, and by the Imaging Sciences Group of the Dartmouth Clinical and Translational Science Institute, under Award Number UL1TR001086 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the funding agencies.

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Author notes

  1. Swaroopa Yerrabothala and Brett L. Gourley have contributed equally to this work.

Authors and Affiliations

  1. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    Swaroopa Yerrabothala, James C. Ford, Stephen J. Guerin, Heather A. Wishart & Deborah L. Ornstein

  2. Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Swaroopa Yerrabothala, James C. Ford, Syed Rakin Ahmed, Stephen J. Guerin, Marc Porter, Heather A. Wishart & Deborah L. Ornstein

  3. Rockwood Clinic, MultiCare Health System, Spokane, WA, USA

    Brett L. Gourley

  4. Harvard Graduate Program in Biophysics, Harvard Medical School, Harvard University, Cambridge, MA, USA

    Syed Rakin Ahmed

  5. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Syed Rakin Ahmed

  6. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Syed Rakin Ahmed

  7. University of Rochester Medical Center, Rochester, NY, USA

    Marc Porter

  8. Cancer Treatment and Diagnosis, Developmental Therapy Program, National Cancer Institute, Bethesda, MD, USA

    Marc S. Ernstoff

  9. University of Virginia School of Medicine, Charlottesville, VA, USA

    Camilo E. Fadul

  10. Department of Pathology & Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, 1 Medical Center Dr., Lebanon, NH, 03756, USA

    Deborah L. Ornstein

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Contributions

BLG, CEF and DLO conceived, designed and conducted the study and analyzed thrombin generation data. SY enrolled subjects, collected and analyzed study data. SY, HAW, CEF and DLO provided critical writing of the manuscript. JCF, SRA, SJG, MP and HAW performed tumor volume analyses. MSE contributed to design of the study and provided laboratory support for specimen collection and processing. All authors have reviewed, revised and approved the final submitted manuscript.

Corresponding author

Correspondence to Deborah L. Ornstein.

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Conflicts of interest

Camilo E. Fadul MD is a member of the Editorial Board of the Journal of Neuro-Oncology. Otherwise, the authors declare they have no relevant conflicts of interest or competing interests.

Ethical approval

This study was approved by the Committee for the Protection of Human Subjects (CPHS) of Dartmouth College (study #D12096).

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All study subjects provided written informed consent for participation in this study.

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Yerrabothala, S., Gourley, B.L., Ford, J.C. et al. Systemic coagulation is activated in patients with meningioma and glioblastoma. J Neurooncol 155, 173–180 (2021). https://doi.org/10.1007/s11060-021-03865-w

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