Swaroopa Yerrabothala1,2, Brett L Gourley3, James C Ford1,2, Syed Rakin Ahmed2,4,5,6, Stephen J Guerin1,2, Marc Porter2,7, Heather A Wishart1,2, Marc S Ernstoff8, Camilo E Fadul9, Deborah L Ornstein10,11,12. 1. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA. 2. Geisel School of Medicine at Dartmouth, Hanover, NH, USA. 3. Rockwood Clinic, MultiCare Health System, Spokane, WA, USA. 4. Harvard Graduate Program in Biophysics, Harvard Medical School, Harvard University, Cambridge, MA, USA. 5. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 6. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 7. University of Rochester Medical Center, Rochester, NY, USA. 8. Cancer Treatment and Diagnosis, Developmental Therapy Program, National Cancer Institute, Bethesda, MD, USA. 9. University of Virginia School of Medicine, Charlottesville, VA, USA. 10. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA. dlornstein@hitchcock.org. 11. Geisel School of Medicine at Dartmouth, Hanover, NH, USA. dlornstein@hitchcock.org. 12. Department of Pathology & Laboratory Medicine, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, 1 Medical Center Dr., Lebanon, NH, 03756, USA. dlornstein@hitchcock.org.
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.
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.
Authors: Daphna Hoefnagel; Lesley E Kwee; Erik H P van Putten; Johan M Kros; Clemens M F Dirven; Ruben Dammers Journal: Clin Neurol Neurosurg Date: 2014-06-11 Impact factor: 1.876
Authors: Rose Fluss; Andrew J Kobets; Julio F Inocencio; Mousa Hamad; Chaim Feigen; David J Altschul; Patrick Lasala Journal: Clin Neurol Neurosurg Date: 2021-01-05 Impact factor: 1.876
Authors: Giorgio Carrabba; Marco Riva; Valeria Conte; Andrea Di Cristofori; Manuela Caroli; Marco Locatelli; Massimo Castellani; Paolo Bucciarelli; Andrea Artoni; Nino Stocchetti; Ida Martinelli; Paolo Rampini Journal: J Neurooncol Date: 2018-03-02 Impact factor: 4.130
Authors: Lorenzo Rinaldo; Desmond A Brown; Adip G Bhargav; Aaron E Rusheen; Ryan M Naylor; Hannah E Gilder; Dileep D Monie; Stephanie J Youssef; Ian F Parney Journal: J Neurosurg Date: 2019-01-04 Impact factor: 5.115
Authors: Thomas J Semrad; Robert O'Donnell; Ted Wun; Helen Chew; Danielle Harvey; Hong Zhou; Richard H White Journal: J Neurosurg Date: 2007-04 Impact factor: 5.115
Authors: Tene A Cage; Kathleen R Lamborn; Marcus L Ware; Anna Frankfurt; Lenna Chakalian; Mitchell S Berger; Michael W McDermott Journal: J Neurooncol Date: 2009-05-09 Impact factor: 4.130
Authors: Christian Valentin Eisenring; Marian Christoph Neidert; Daniel Sabanés Bové; Leonhard Held; Johannes Sarnthein; Niklaus Krayenbühl Journal: PLoS One Date: 2013-11-14 Impact factor: 3.240