Circulating, Extracellular Vesicle-Associated Tissue Factor in Cancer Patients with and without Venous Thromboembolism.

Abstract

Cancer is characterized by chronic inflammation and hypercoagulability, with an excess of venous thromboembolism (VTE). Tissue factor, the initiator of blood coagulation, circulates associated with extracellular vesicles (EV-TF). Studies investigating EV-TF between cancer-associated and non-cancer-associated VTE are lacking. We therefore compared EV-TF in unprovoked VTE (U-VTE), cancer-associated VTE (C-VTE), and cancer without VTE (C-w/o VTE). We also investigated interleukin-6 (IL-6) levels between the same groups. The final population included 68 patients (U-VTE: n = 15; C-VTE: n = 24; C-w/o VTE: n = 29). All patients with VTE were enrolled within 48 h of diagnosis; non-VTE patients were recruited in the oncologic outpatient services. EV were isolated by differential centrifugation from 4 mL of peripheral blood; the final EV pellet (16,000× g for 45 min) was resuspended in 100 μL saline and tested for TF using a one-step clotting assay. There was a statistically significant difference for higher EV-TF in C-VTE and C-w/o VTE compared to U-VTE (p = 0.024; Kruskal-Wallis test). There was no significant difference between C-VTE and C-w/o VTE. Moreover, we did not find any difference in IL-6 levels. These preliminary data suggest that cancer represents, per se, a strong driver of EV-TF generation.