Neutrophil Extracellular Traps Promote Hypercoagulability in Patients With Sepsis

Background: Patients with sepsis commonly exhibit a hypercoagulability with high risk of venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) are found to trigger inflammation and coagulation. We aim to determine whether NETs promoted the hypercoagulability and early anticoagulation reduced NETs releasing during sepsis. Methods: In this prospective study, septic patients between September 2013 and June 2015 were included. Patients of age <18 years, acute organ failure, pregnancy, coagulation disorders, receiving anticoagulation before admission were excluded. Blood was sampled in 52 sepsis and 10 non-sepsis patients and 40 healthy controls, clinical, and hematological parameters were collected. The ability of plasma and platelets to prime neutrophils to release NETs and contribution of NETs to coagulation were assessed. NETs releasing was compared in patients with or without early coagulation, and its correlation with the risk of VTE was also evaluated. Results: NETs formation in septic patients was significantly higher than controls and non-sepsis patients. Neutrophils from septic patients had significantly enhanced NETs releasing compared with those from controls or non-sepsis patients. Plasma or platelets obtained from patients induced control neutrophils to release NETs. Notably, NETs released by neutrophils from septic patients significantly increased the potency of control plasma to generate thrombin and fibrin, and this effect was attenuated by administration of DNase I. Post-treatment NETs releasing in septic patients receiving early anticoagulation within 6 h was significantly lower than patients without early anticoagulation. The NETs formation correlated positively with the VTE risk, rather than the parameters of inflammation or disease severity. Conclusions: The systemic inflammation during sepsis primes neutrophils to release NETs with increased risk of VTE. Early anticoagulation (6 h) reduces NETs releasing and may improve the coagulopathy of septic patients.