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This review integrates recent mechanistic advances linking damage-associated molecular patterns (DAMPs), endothelial dysfunction, and intravascular coagulation. Endogenous alarmins, such as high-mobility group box 1, histones, and mitochondrial DNA, engage in pattern recognition (Toll-like receptors, receptor for advanced glycation end products) to propagate leukocyte activation, platelet aggregation, and endothelial disruption. The resulting loss of critical endothelial anticoagulant molecules (thrombomodulin, endothelial cell protein C receptor, antithrombin) and glycocalyx degradation convert the vascular endothelium into a procoagulant interface. Complement activation and protease-activated receptor signaling reinforce this loop, producing microvascular thrombosis, capillary leakage, and organ ischemia. Platelet\u2013leukocyte aggregates and neutrophil extracellular traps (NETs) serve as intravascular scaffolds for fibrin deposition, thereby propagating disseminated intravascular coagulation (DIC). Targeted interventions, including recombinant thrombomodulin, antithrombin supplementation, neutralization of NETs and DAMPs, complement blockade, and endothelial-protective strategies, seek to restore vascular homeostasis. A multidomain biomarker approach integrating DAMPs, endothelial markers, and coagulation indices, combined with machine learning\u2013based phenotyping, may enable precision stratification of sepsis endotypes. The convergence of DAMP signaling, immune activation, and coagulation underlies the pathophysiologic continuum from sepsis-induced coagulopathy to DIC. Therapeutically interrupting this axis represents the most promising avenue toward personalized, mechanism-driven treatment in sepsis.<\/jats:p>","DOI":"10.1055\/a-2776-5999","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:31:58Z","timestamp":1766190718000},"source":"Crossref","is-referenced-by-count":10,"title":["Damage-associated Molecular Patterns, Immunothrombosis, and Intravascular Inflammation in Sepsis: A Narrative Integrative Review"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-4088","authenticated-orcid":false,"given":"Toshiaki","family":"Iba","sequence":"additional","affiliation":[{"name":"Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan"},{"name":"Faculty of Medical Science, Juntendo University, Urayasu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Helms","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit \u2013 NHC, INSERM (French National Institute of Health and Medical Research), Strasbourg University (UNISTRA), Strasbourg University Hospital, UMR 1260, Regenerative Nanomedicine (RNM), Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0895-6800","authenticated-orcid":false,"given":"Hideshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Nagakari","sequence":"additional","affiliation":[{"name":"Department of Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4141-9062","authenticated-orcid":false,"given":"Koichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Surgery, Juntendo University Graduate School of Medicine, Juntendo Shizuoka Hospital, Urayasu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-4747","authenticated-orcid":false,"given":"Ricard","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Intensive Care Department, Hospital Universitari Vall d'Hebron Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4962","authenticated-orcid":false,"given":"Jerrold H.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, 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