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A Novel Assay for Neutrophil Extracellular Traps (NETs) Formation Independently Predicts Disseminated Intravascular Coagulation and Mortality in Critically Ill Patients

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Abrams, Simon T, Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Alhamdi, Yasir, Alsabani, Mohmad, Lane, Steven, Welters, Ingeborg D, Wang, Guozheng and Toh, Cheng-Hock (2019) 'A Novel Assay for Neutrophil Extracellular Traps (NETs) Formation Independently Predicts Disseminated Intravascular Coagulation and Mortality in Critically Ill Patients'. American Journal of Respiratory and Critical Care Medicine, Vol 200, Issue 7, pp. 869-880.

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Abstract

Rational: Neutrophil extracellular traps (NETs) are important in the host defence against infection, but also promote intravascular coagulation and multi-organ failure (MOF) in animal models. Its clinical significance remains unclear and available assays for patient care lack specificity and reliability. Objectives: To establish a novel assay and test its clinical significance Methods: A prospective cohort of 341 consecutive adult ICU patients was recruited. The NETs-forming capacity of ICU admission blood samples was semi-quantified by directly incubating patient plasma with isolated neutrophils ex vivo. The association of NETs–forming capacity with sequential organ failure assessment (SOFA) scores, disseminated intravascular coagulation (DIC) and 28-day mortality were analysed and compared with available NETs assays. Measurements and Main Results: Using the novel assay, we could stratify ICU patients into 4 groups with absent (22.0%), mild (49.9%), moderate (14.4%) and strong (13.8%) NETs formation, respectively. Strong NETs formation was predominantly found in sepsis (P <0.0001). Adjusted by APACHE II, multivariate regression showed that the degree of NETs formation could independently predict DIC and mortality whereas other NETs assays, e.g. cell-free DNA, myeloperoxidase and myeloperoxidase-DNA complexes, could not. IL-8 levels were found to be strongly associated with NETs formation and inhibiting IL-8 significantly attenuated NETosis. MAPK activation by IL-8 has been identified as a major pathway of NETs formation in patients. Conclusions: This assay directly measures the NETs-forming capacity in patient plasma. This could guide clinical management and enable identification of NETs-inducing factors in individual patients for targeted treatment and personalised ICU medicine.

Item Type: Article
Subjects: QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1164/rccm.201811-2111OC
Depositing User: Stacy Murtagh
Date Deposited: 06 Jun 2019 11:04
Last Modified: 03 Oct 2019 14:45
URI: https://archive.lstmed.ac.uk/id/eprint/10972

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