Dataset Information

A Novel Assay for Neutrophil Extracellular Trap Formation Independently Predicts Disseminated Intravascular Coagulation and Mortality in Critically Ill Patients.

ABSTRACT: Rationale: Neutrophil extracellular traps (NETs) are important in the host defense against infection, but they also promote intravascular coagulation and multiorgan failure in animal models. Their 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 NET-forming capacity of ICU admission blood samples was semiquantified by directly incubating patient plasma with isolated neutrophils ex vivo. The association of NET-forming capacity with Sequential Organ Failure Assessment scores, disseminated intravascular coagulation, and 28-day mortality was analyzed and compared with available NET assays.Measurements and Main Results: Using the novel assay, we could stratify ICU patients into four groups with absent (22.0%), mild (49.9%), moderate (14.4%), and strong (13.8%) NET formation, respectively. Strong NET formation was predominantly found in sepsis (P < 0.0001). Adjusted by Acute Physiology and Chronic Health Evaluation II score, multivariate regression showed that the degree of NET formation could independently predict disseminated intravascular coagulation and mortality, whereas other NET assays (e.g., cell-free DNA, myeloperoxidase, and myeloperoxidase-DNA complexes) could not. IL-8 concentrations were found to be strongly associated with NET formation, and inhibiting IL-8 significantly attenuated NETosis. Mitogen-activated protein kinase activation by IL-8 has been identified as a major pathway of NET formation in patients.Conclusions: This assay directly measures the NET-forming capacity in patient plasma. This could guide clinical management and enable identification of NET-inducing factors in individual patients for targeted treatment and personalized ICU medicine.

SUBMITTER: Abrams ST

PROVIDER: S-EPMC6812439 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionSince disseminated intravascular coagulation (DIC) was first described, it has been considered a serious disease of the coagulation system and a major challenge to clinicians. Currently, several important knowledge gaps remain. The DANish Disseminated Intravascular Coagulation (DANDIC) Cohort Study will aim to answer questions regarding the incidence and mortality of patients with DIC including time trends. The study will also identify prognostic factors that may guide personalised prevention and treatment. Furthermore, the study will describe treatment patterns and the safety and effectiveness of various treatment modalities.Methods and analysisWe will establish the DANDIC Cohort using data collected in daily clinical practice from the Central Denmark Region, which covers approximately 1.3 million residents. The study period will encompass 1 January 2011 through 1 July 2021. Potential DIC cases will be identified from the hospital laboratory database, based on coagulation biomarkers, and diagnoses will be adjudicated by medical experts. The dataset will be enriched with detailed clinical data from electronic medical charts on aetiologies, bleeding, microthrombus formation, organ failure, thrombosis, treatments and comorbidities. The dataset will also take advantage of in-hospital data with longitudinal information on laboratory records, transfusions, microbiology and treatments. It will be possible to merge this dataset with other unique Danish health registries with more than 10 years of virtually complete follow-up. The project will use state-of-the-art epidemiological and biostatistical methods.Ethics and disseminationThe project has been approved by the Danish Patient Safety Authority (31-1521-452), the Central Denmark Region (1-45-70-83-21), the Danish Data Protection Agency (1-16-02-258-21) and all the hospital chairs. Register-based studies require no ethical approval in Denmark. The results will be disseminated in international peer-reviewed journals.

Project description:IntroductionDisseminated intravascular coagulation (DIC) is a common and serious condition that can lead to poor outcomes in critically ill patients. To make a correct diagnosis and improve the outcome of patients with DIC, several organisations have put forward DIC scoring systems. However, which criteria is the best to use for diagnosing DIC remains a continuing controversy even though many studies have been conducted to validate the diagnostic accuracy of each DIC scoring system.Methods and analysisWe will conduct a systematic review and meta-analysis of the diagnostic accuracy of DIC criteria for the prediction of mortality in critically ill adult patients. The primary objective is to assess the predictive values of the DIC criteria of Japanese Association for Acute Medicine, International Society on Thrombosis and Haemostasis, Japanese Ministry of Health and Welfare, Korean Society on Thrombosis and Hemostasis and Chinese Diagnostic Scoring System for 28-day mortality. We will search electronic bibliographic databases such as MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data. We will report study characteristics and assess methodological quality using the Quality of Diagnostic Accuracy Studies-II tool. If pooling is appropriate, we will compute parameter estimates using bivariate random-effects and hierarchical summary receiver operating characteristic models to produce summary receiver operating curves, summary operating points (pooled sensitivity and specificity) and 95% confidence regions around the summary operating points. Clinical and methodological subgroup and sensitivity analyses will be performed to explore heterogeneity.Ethics and disseminationThis systematic review will help physicians diagnose DIC accurately and improve their clinical practice in critically ill settings. Approval from an ethics committee is not required. The findings will be disseminated through publication in a peer-reviewed journal.Prospero registration numberCRD42017079350.

Dataset Information

A Novel Assay for Neutrophil Extracellular Trap Formation Independently Predicts Disseminated Intravascular Coagulation and Mortality in Critically Ill Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets