Circulating extracellular vesicle tissue factor activity is associated with disseminated intravascular coagulation in 2 cohorts of patients with sepsis

Background Disseminated intravascular coagulation (DIC) occurs in a variety of diseases and syndromes. Platelet count, prothrombin time, and levels of fibrinogen and D-dimer are used to determine if a patient has DIC. The tissue factor (TF)/factor VIIa complex plays a central role in the activation of coagulation in sepsis. In Gram-negative sepsis, lipopolysaccharide induces TF expression in monocytes and release TF-positive extracellular vesicles (EV). Objective To determine if EV-TF activity is associated with DIC in patients with sepsis. Patient/Methods We studied two cohorts of patients with sepsis: a cohort of sequential patients that included 143 patients without DIC and 45 patients with DIC, and a cohort of selected patients that included 39 patients without DIC and 36 patients with DIC. The first cohort had longitudinal samples, and the second cohort had samples from pre-DIC patients (who developed DIC during the study). Healthy subjects were used as controls. Plasma EV-TF activity was measured using an in-house assay. We used the updated 2025 International Society on Thrombosis and Haemostasis DIC score. Results and Conclusions EV-TF activity was significantly higher in patients with sepsis compared to healthy controls. There was no significant difference in the level of EV-TF activity between pre-DIC patients and patients without DIC. Importantly, EV-TF activity was associated with DIC in both cohorts of patients with sepsis. We observed a time-dependent decrease in EV-TF activity in patients with DIC. Our study suggests that increased levels of circulating EV-TF activity contribute to the activation of coagulation in patients with sepsis.