Evidence of Netosis in Septic Shock-Induced Disseminated Intravascular Coagulation

Abstract

Introduction: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity, and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic shock-induced DIC.

Methods: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study. Vascular cell activation was assessed by microparticle (MP) measurement. NETosis was investigated at days 1, 3, and 7 using two different approaches: probing and measurement of neutrophil DNA decompaction by neutrophil-side fluorescence light (NEUT-SFL) as recorded by an automated blood cell cytometer and the assessment of nucleosomes and NETs (DNA-bound myeloperoxidase, DNA-MPO).

Results: Endothelial-derived CD105-MPs, leucocyte-derived CD11a-MPs/leucocyte, and neutrophil-derived CD66b-MPs/neutrophil count ratios significantly increased in DIC compared with non-DIC patients, indicating on-going cell activation (P <0.05). NEUT-SFL, indicating DNA decompaction, was significantly higher in DIC patients. Circulating nucleosomes and DNA-MPO were increased in DIC patients (P <0.05). There were significant correlations between: nucleosomes and NETs (r = 0.397, P = 0.004), NEUT-SFL and nucleosomes (r = 0.243, P = 0.032), NEUT-SFL and DNA-MPO (r = 0.266, P = 0.024).

Conclusion: NEUT-SFL, NETs, and elevated nucleosome concentrations were all correlated to DIC (P <0.05). We have shown that NETosis is significantly correlated to septic shock-induced DIC.