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 (F)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 (EVs). Objective: This study determined whether EV-TF activity is associated with DIC in patients with sepsis. Methods: We studied 2 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 taken, and the second cohort had samples taken 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 (ISTH) DIC score. Results: EV-TF activity was significantly higher in patients with sepsis than in 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. Conclusion: Our study suggests that increased levels of circulating EV-TF activity contribute to the activation of coagulation in patients with sepsis.