Abstract
This proof-of-concept study aimed to evaluate a novel method of flow cytometry-based quantification of neutrophil extracellular traps (NETs) in septic shock patients and to identify possible interactions between the number of free-circulating NETs and alterations of the coagulatory system. Patients suffering from septic shock, a matched control group (CTRL), and patients suffering from systemic inflammation after cardiac (CABG) or major abdominal surgery (MAS) were enrolled in this prospective proof-of-concept study. Compared to the matched controls, free-circulating NETs were significantly elevated in septic shock and postsurgical patients (data are presented in median (IQR)); septic shock: (2.7 (1.9–3.9); CABG: 2.7 (2.1–3.7); MAS: 2.7 (2.1–3.9); CTRL: 1.6 (1–2); CTRL vs. septic shock: p = 0.001; CTRL vs. CABG: p < 0.001; CTRL vs. MAS: p < 0.001). NETs correlated positively with FIBTEM mean clot firmness (MCF) in septic shock patients (r = 0.37, p < 0.01) while they correlated negatively in surgical patients (CABG: r = −0.28, p < 0.01; MAS: r = −0.25, p = 0.03). Flow-cytometric quantification of NETs showed a significant increase in free-circulating NETs under inflammatory conditions. Furthermore, this study hints to an association of the number of NETs with hypercoagulation in septic shock patients and hypocoagulation in surgery-induced inflammation.
Highlights
Despite tremendous efforts to develop new diagnostic and therapeutic approaches, septic shock still remains associated with high mortality
Since neutrophil extracellular traps (NETs) are associated with sepsis-associated coagulopathy, our study aimed to investigate whether the amount of free-circulating NETs is associated with clinically relevant coagulopathies in septic shock and postsurgical systemic inflammation [15,18,20,21,52,53]
Therapeutic heparinization occurred only in a small number of cases, a bias effect cannot be ruled out. This proof-of-concept study investigated the value of flow-cytometric NET quantification in septic shock patients as well as in patients suffering from postsurgical systemic inflammation
Summary
Despite tremendous efforts to develop new diagnostic and therapeutic approaches, septic shock still remains associated with high mortality. Patients suffering from septic coagulopathy are considered to be at high risk for limited outcome [1,2]. This is recognized by the Sepsis-3 definition, which highlights that the hosts pathophysiological reactions to a pathogen are determined by the severity of organ failure [3]. Despite ambitious approaches, no specific treatment of SAC could be successfully established [6,7,8] For this reason, early detection of sepsis and SAC are crucial for the survival of patients. By investigating the underlying interactions between the innate immune and coagulatory systems, immunothrombosis has been identified as an important trigger of systemic inflammation and offers new diagnostic and therapeutic approaches for the management of septic coagulopathy [14,15,16,17]
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