Role of circulating mitochondria in venous thrombosis in glioblastoma

Ricardo Gonzalez-Delgado; Nina M Muñoz; Wendolyn Carlos-Alcalde; Min Soon Cho; Hani Lee; Jeff Jin; Victoria Serpas; Olga Gorlova; Rahul A Sheth; Vahid Afshar-Kharghan

doi:10.1016/j.jtha.2023.04.036

Role of circulating mitochondria in venous thrombosis in glioblastoma

J Thromb Haemost. 2023 Aug;21(8):2202-2212. doi: 10.1016/j.jtha.2023.04.036. Epub 2023 May 11.

Authors

Affiliations

¹ Section of Benign Hematology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
² Department of Interventional Radiology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³ Information Services, Enterprise Development & Integration, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁴ Department of GI Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁵ Section of Epidemiology and Population Science, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
⁶ Department of Interventional Radiology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: rasheth@mdanderson.org.
⁷ Section of Benign Hematology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: vakharghan@mdanderson.org.

Abstract

Background: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy.

Objectives: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state.

Methods: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis.

Results: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: 2.8 × 10⁷ mitochondria/mL; GBM without VTE, 1.9 × 10⁷ mitochondria/mL) than that in healthy control subjects (n = 17) (0.3 × 10⁷ mitochondria/mL). Interestingly, patients with GBM and VTE (n = 41) had a higher mitochondria concentration than patients with GBM without VTE (n = 41). In a murine model of inferior vena cava stenosis, intravenous delivery of mitochondria resulted in an increased rate of venous thrombosis compared with that in controls (70% and 28%, respectively). Mitochondria-induced venous thrombi were neutrophil-rich and contained more platelets than those in control thrombi. Furthermore, as mitochondria are the only source of cardiolipin in circulation, we compared the concentration of anticardiolipin immunoglobulin G in plasma samples of patients with GBM and found a higher concentration in patients with VTE (optical density, 0.69 ± 0.04) than in those without VTE (optical density, 0.51 ± 0.04).

Conclusion: We concluded that mitochondria might play a role in the GBM-induced hypercoagulable state. We propose that quantifying circulating mitochondria or anticardiolipin antibody concentrations in patients with GBM might identify patients at increased risk of VTE.

Keywords: anticardiolipin antibody; glioblastoma; mitochondria; neutrophils; venous thrombosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Constriction, Pathologic / complications
Glioblastoma* / complications
Mice
Risk Factors
Venous Thromboembolism*
Venous Thrombosis* / complications

Abstract

Publication types

MeSH terms

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