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.
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.
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.
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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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.
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.
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.
This study was approved by the Committee for the Protection of Human Subjects (CPHS) of Dartmouth College (study #D12096).
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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
- Coagulation activation
- Thrombin generation (TG)
- Glioblastoma multiforme (GBM)
- Brain tumors