Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients

Abstract Background: Nonalcoholic steatohepatitis (NASH) patients are at a high risk of developing venous thromboembolism, with a high rate of morbidity and mortality. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in patients with NASH remains unclear. Our study aimed to investigate the formation of NETs in NASH patients stimulated by specific pro-inflammatory factors. Moreover, we evaluated the pivotal role of NETs in the induction of hypercoagulability in NASH and the interaction between NETs and endothelial injury. Method: The levels of the NETs biomarkers were evaluated in the plasma samples of 27 NASH patients and 18 healthy subjects. The formation of NETs was visualized using immunofluorescence microscopy. The PCA of the NETs was assessed using coagulation time, purified coagulation complex, and fibrin formation assays. Confocal microscopy was further used to evaluate the interactions between the NETs and HUVECs. Results: The levels of NETs markers in the plasma of NASH patients were significantly higher than healthy controls. NETs derived from NASH enhanced thrombin and fibrin formation and significantly reduced CT (p Conclusion: Our results revealed the primary role of NETs in promoting the hypercoagulable state in NASH patients. Methods that prevent the formation of NETs may be a novel approach for the prevention and treatment of NASH.