Extracellular vesicle tissue factor and tissue factor pathway inhibitor are independent discriminators of sepsis-induced coagulopathy

Abstract

Background

Sepsis-induced disseminated intravascular coagulopathy (DIC) remains a challenging clinical entity associated with significant morbidity and mortality. Endothelial injury or activation and extracellular vesicles (EV) are postulated as important determinants of DIC.

Objectives

The aim of this study was to test the discriminatory ability of E-selectin, EV, tissue factor (TF) and TF pathway inhibitor (TFPI) in sepsis-induced coagulopathy.

Methods

In this prospective, single-center study, we collected plasma samples within 24 hours after sepsis diagnosis and followed these patients for 5 consecutive days. Overt DIC was determined by the International Society on Thrombosis and Haemostasis (ISTH) DIC score. Eighty-seven sepsis patients were recruited (35 with overt DIC) who presented with increased levels of EV, EV-associated TF procoagulant activity (TF-PCA), E-selectin, TF, and TFPI at admission compared with healthy subjects.

Results

Only TFPI levels and TF-PCA discriminated between sepsis patients with or without DIC (area under the curve = 0.76; P = .0002). Increased TF-PCA was not sensitive in detecting sepsis-associated DIC; however, levels above 1.38 pg/mL showed high specificity in this cohort (sensitivity 27%, specificity 95%). The hazard ratio to progress to DIC over 5 days was 1.14 (95% CI, 0.64-2.07) for TF-PCA levels of 0.5 pg/mL or higher and 3.18 (95% CI, 1.74-5.79) for TFPI levels of 22.28 ng/mL or higher at admission.

Conclusion

These findings highlight the pivotal roles of TF-PCA and TFPI in an early phase of sepsis-induced DIC. Only EV-associated and functionally active TF and not TF antigen levels showed a predictive potential regarding DIC. These novel results might support the improvement of diagnostic or even therapeutic strategies to mitigate the devastating consequences of DIC in septic patients.