Role of circulating mitochondria in venous thrombosis in glioblastoma.

Using plasma samples of 82 patients with GBM, we found that GBM patients had a higher number of mitochondria in their plasma (GBM with VTE: 2.8 × 10 mitochondria/ml, GBM without VTE: 1.9 × 10 mitochondria/ml) than control healthy subjects (n=17)(0.3 × 10 mitochondria/ml). Interestingly, patients with GBM and VTE (n=41) had a higher mitochondria concentration than GBM patients without VTE (n=41). In a murine model of IVC stenosis, intravenous delivery of mitochondria resulted in an increased rate of venous thrombosis compared to controls (70% and 28%, respectively). Mitochondria-induced venous thrombi were neutrophil-rich and contained more platelets than control thrombi. Furthermore, as mitochondria are the only source of cardiolipin in circulation, we compared the concentration of anticardiolipin IgG in plasma samples of GBM patients and found a higher concentration in patients with VTE (OD = 0.69 ± 0.04) than those without VTE (OD: 0.51 ± 0.04). We concluded that mitochondria might play a role in the GBM-induced hypercoagulable state. We propose quantifying circulating mitochondria or anticardiolipin antibody concentrations in GBM patients might identify patients at increased risk for VTE.