Sepsis-induced coagulopathy: recent insights on the role and clinical application of neutrophil extracellular trap formation

Sep 30, 2026

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Sepsis is a life-threatening syndrome driven by an uncontrolled immune response to infection, producing immunothrombosis and disseminated intravascular coagulation (DIC) through neutrophil extracellular trap (NET) formation. This case-control study evaluated whether NET-related biomarkers can serve as diagnostic, prognostic, and therapeutic indicators in critical care. A 7-day follow-up included 138 sepsis patients for mortality assessment and 80 age- and sex-matched healthy controls. Findings link sepsis histones to inflammatory response and coagulopathy/DIC. Myeloperoxidase predicts short-term mortality regardless of DIC status, with concurrent MPO and histone elevations suggesting urgent need for NET inhibitors to reduce thrombotic events and improve outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Sepsis, coagulopathy, and DIC

Immunothrombosis and NETosis mechanisms

Roles of MPO and histones

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Sepsis-induced coagulopathy: recent insights on the role and clinical application of neutrophil extracellular trap formation Shams ElDoha Galal ElDin Zaiema1􀀍, Nahela Ahmed Shalaby1, Toka Hassaan Mohamed1, Aya Ali Mahmoud Bayoumy2 & Raghda El Sayed Abdel Monem Galal1 Sepsis is characterized by life-threatening organ dysfunction caused by an uncontrolled immune response to infection. Neutrophils play a vital role in this process, which can lead to immunothrombosis and disseminated intravascular coagulation (DIC) via the formation of neutrophil extracellular traps (NETs). This study aimed to validate the impact of NETs biomarkers in evaluating their potential as diagnostic, prognostic, and therapeutic indicators in critical care for patients with sepsis. We conducted a case-control study with a 7-day follow-up to assess mortality in 138 sepsis patients, focusing specifically on the occurrence of DIC. Additionally, 80 healthy volunteers, matched by age and sex, served as controls. Our findings reveal a strong connection between histones in sepsis and both the initial inflammatory response and sepsis-related coagulopathy/DIC. Furthermore, we found that myeloperoxidase can effectively predict short-term mortality among sepsis patients, regardless of their DIC status. This study highlights a concerning simultaneous increase inmyeloperoxidase and histones (thresholds of > 84.9 ng/ml and > 126.4 ng/ml, respectively), which may serve as vital indicators indicating the urgent need for NETs inhibitors in sepsis treatment. Applying this approach, we anticipate a significant reduction in thrombotic events and mortality, thereby enhancing patient care and outcomes in the management of critical sepsis. Keywords Sepsis-induced NETosis, Myeloperoxidase (MPO), Histones (HIST), Immunothrombosis, Response, Short-term mortality, Sepsis management in critical care units Abbreviations NETs MPO HIST Cit-HIST-H3 ROS ELANEATSICDICSIRS SOFA JAAM-2 NLRFDPINRPAI-1 TTPHUS PCT Neutrophil extracellular traps Myeloperoxidase Histones Human citrullinated histone H3 Reactive oxygen species Neutrophil elastase Antithrombin Sepsis-induced coagulopathy Disseminated intravascular coagulation Systemic inflammatory response syndrome Sequential organ failure assessment Japanese association for acute medicine modified score Neutrophil-to-lymphocyte ratio Fibrin degradation products International normalized ratio Plasminogen activator inhibitor-1 Thrombotic thrombocytopenic purpura Hemolytic uremic syndrome Pro-calcitonin 1Department of Clinical Pathology, Ain Shams University, Cairo, Egypt. 2Department of Anaesthesia and ICU, Ain Shams University, Cairo, Egypt. 􀀍 [email: ShamsZaeima@med.asu.edu.eg](email: ShamsZaeima@med.asu.edu.eg) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) CRP C-reactive protein ELISA Enzyme-linked immunosorbent assay PLT Platelets Hb Hemoglobin APLS Antiphospholipid syndrome Sepsis is a complex syndrome triggered by infections that can result in organ dysfunction, as indicated by an elevated Sequential Organ Failure Assessment (SOFA) score1. A key component of sepsis is sepsis-induced coagulopathy (SIC), which arises from an uncontrolled acquired immunoinflammatory response and the stimulation of coagulation mechanisms. Overt disseminated intravascular coagulation (DIC) represents an advanced stage of this condition, characterized by extensive coagulation and organ failure2,3. Recent studies have highlighted the crucial roles of immune cells, including neutrophils and monocytes, in promoting blood clot formation within blood vessels, a phenomenon known as immunothrombosis4. When endothelial cells encounter pathogens, they increase their adhesion capacity, enabling the attachment of leukocytes. Activated monocytes release tissue factor, which initiates coagulation and fibrin fiber fo

FAQs

What role do neutrophil extracellular traps (NETs) play in sepsis-induced coagulopathy?

NETs contribute to coagulopathy by interacting with biological systems, obstructing fibrinolysis, and disrupting natural anticoagulant mechanisms, which can lead to thrombocytopenia.

How did the study assess the clinical relevance of NET biomarkers?

The study used a case-control design with a 7-day follow-up, measuring outcomes including mortality in 138 sepsis patients and comparing them with 80 matched healthy controls.

Which biomarker was reported to predict short-term mortality in sepsis patients?

Myeloperoxidase (MPO) effectively predicted short-term mortality among sepsis patients regardless of their DIC status.

Sep 30, 2026

Upload by Levi