Abstract Number: OC 14.1
Meeting: ISTH 2020 Congress
Background: Neutrophils are the first line of defence against bacterial infection and neutrophil extracellular traps (NETs) formation is an important protective mechanism. NETs can also cause harm by promoting intravascular coagulation and multi-organ failure (MOF) in animal models. Although increasingly considered as important therapeutic targets, there is no robust and specific measure of NETs formation to inform clinical care and enable precision medicine in intensive care unit (ICU) patients.
Aims: The aim of this study is to establish a novel assay for measuring NETs and assess its clinical significance.
Methods: Consecutive adult ICU patients (n=341) were prospectively enrolled following written informed consent. Complementary, mice models of sepsis (caecal ligation and puncture (CLP) or intraperitoneal injection of Escherichia coli), were performed without or with anti-NETs therapy.
Results: NETs were directly induced by heterologous healthy neutrophils incubated with plasma from ICU patients, but not healthy donors. We stratified ICU patients into 4 groups, those with absent (22.0%), mild (49.9%), moderate (14.4%) and strong (13.8%) NETs formation, respectively. Strong NETs were predominantly in sepsis patients (P< 0.0001) and associated with SOFA scores. Adjusted by APACHE II, multivariate regression showed that NETs formation on ICU admission independently predicted DIC and mortality. Interleukin (IL)-8 levels were associated with NETs formation, inhibiting IL-8 significantly attenuated NETosis. In septic mice, NETs positive staining was predominantly in the lungs, and could be monitored by our non-invasive NETs assay. NETs were associated with fibrin deposition within the lungs and increases in lung injury scores, along with circulating markers of liver, kidney and cardiac injury, which was inhibited by targeting IL-8.
Conclusions: This NETs assay could guide clinical management and enable targeted treatment and personalised ICU medicine. IL-8 is a major driving factor of NETs in sepsis, with anti-IL-8 therapy significantly reducing NETs-induced organ damage and mortality in septic mice.
To cite this abstract in AMA style:Abrams S, Morton B, Alhamdi Y, Alsabani M, Cheng Z, Lane S, Welters I, Wang G, Toh C-. A Novel Neutrophil Extracellular Traps (NETs) Assay Predicts DIC and Stratifies Patients with Sepsis for Anti-IL-8 Therapy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/a-novel-neutrophil-extracellular-traps-nets-assay-predicts-dic-and-stratifies-patients-with-sepsis-for-anti-il-8-therapy/. Accessed November 26, 2020.
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