{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:20:28Z","timestamp":1792718428441,"version":"4.5.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016156","name":"U.S. Army Medical Research and Development Command","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Complementopathy, endotheliopathy, and coagulopathy following a traumatic injury are key pathophysiological mechanisms potentially associated with multiple-organ failure (MOF) and mortality. However, the heterogeneity in the responses of complementopathy, endotheliopathy, and coagulopathy to trauma, the nature and extent of their interplay, and their relationship to clinical outcomes remain unclear. Fifty-four poly-trauma patients were enrolled and divided into three subgroups based on their ISS. Biomarkers in blood plasma reflecting complement activation, endothelial damage, and coagulopathy were measured starting from admission to the emergency department and at 3, 6, 12, 24, and 120 hours after admission. Comparative analyses showed that severely injured patients (ISS&amp;gt;24) were associated with longer days on mechanical ventilation, in the intensive care unit and hospital stays, and a higher incidence of hyperglycemia, bacteremia, respiratory failure and pneumonia compared to mildly (ISS&amp;lt;16) or moderately (ISS=16-24) injured patients. In this trauma cohort, complement was activated early, primarily through the alternative complement pathway. As measured in blood plasma, severely injured patients had significantly higher levels of complement activation products (C3a, C5a, C5b-9, and Bb), endothelial damage markers (syndecan-1, sTM, sVEGFr1, and hcDNA), and fibrinolytic markers (D-dimer and LY30) compared to less severely injured patients. Severely injured patients also had significantly lower thrombin generation (ETP and peak) and lower levels of coagulation factors (I, V, VIII, IX, protein C) than less severely injured patients. Complement activation correlated with endothelial damage and hypocoagulopathy. Logistic regression analyses revealed that Bb &amp;gt;1.57 \u03bcg\/ml, syndecan-1 &amp;gt;66.6 ng\/ml or D-dimer &amp;gt;6 mg\/L at admission were associated with a higher risk of MOF\/mortality. After adjusting for ISS, each increase of the triadic score defined above (Bb&amp;gt;1.57 \u00b5g\/ml\/Syndecan-1&amp;gt;66.6 ng\/ml\/D-dimer&amp;gt;6.0mg\/L) was associated with a 6-fold higher in the odds ratio of MOF\/death [OR: 6.83 (1.04-44.96, P=0.046], and a 4-fold greater in the odds of infectious complications [OR: 4.12 (1.04-16.36), P=0.044]. These findings provide preliminary evidence of two human injury response endotypes (traumatized triad and non-traumatized triad) that align with clinical trajectory, suggesting a potential endotype defined by a high triadic score. Patients with this endotype may be considered for timely intervention to create a pro-survival\/organ-protective phenotype and improve clinical outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2022.991048","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T12:17:45Z","timestamp":1666268265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Traumatized triad of complementopathy, endotheliopathy, and coagulopathy \u02d7 Impact on clinical outcomes in severe polytrauma patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhangsheng","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan D.","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milomir O.","family":"Simovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara L.","family":"Fraker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas S.","family":"Cancio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Cap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Wade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurandir J.","family":"DalleLucca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"B1","unstructured":"Key injury and violence data2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0064-8","article-title":"Innate immune responses to trauma","volume":"19","author":"Huber-Lang","year":"2018","journal-title":"Nat Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31825f018d","article-title":"Innate immune dysfunction in trauma patients: from pathophysiology to treatment","volume":"117","author":"Asehnoune","year":"2012","journal-title":"Anesthesiology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60687-5","article-title":"The systemic immune response to trauma: an overview of pathophysiology and treatment","volume":"384","author":"Lord","year":"2014","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001603","article-title":"The role of extracellular adenosine triphosphate in ischemic organ injury","volume":"44","author":"Zhao","year":"2016","journal-title":"Crit Care Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00872-x","article-title":"Complement as driver of systemic inflammation and organ failure in trauma, burn, and sepsis","volume":"43","author":"Mannes","year":"2021","journal-title":"Semin Immunopathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.04.005","article-title":"Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation - closing pandora's box","volume":"28","author":"Huber-Lang","year":"2016","journal-title":"Semin Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15245","article-title":"Complement in trauma-traumatised complement","volume":"178","author":"Huber-Lang","year":"2021","journal-title":"Br J Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.molimm.2006.06.020","article-title":"The role of complement in biomaterial-induced inflammation","volume":"44","author":"Nilsson","year":"2007","journal-title":"Mol Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3182471795","article-title":"Early complementopathy after multiple injuries in humans","volume":"37","author":"Burk","year":"2012","journal-title":"Shock"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-636423","article-title":"Advances in the understanding of trauma-induced coagulopathy","volume":"128","author":"Chang","year":"2016","journal-title":"Blood"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(96)00071-9","article-title":"The kallikrein\/kinin system and kinin antagonists in trauma","volume":"33","author":"Rodell","year":"1996","journal-title":"Immunopharmacology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00543","article-title":"Targeting complement pathways in polytrauma- and sepsis-induced multiple-organ dysfunction","volume":"10","author":"Karasu","year":"2019","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02050","article-title":"Complement after trauma: Suturing innate and adaptive immunity","volume":"9","author":"Chakraborty","year":"2018","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/ams2.426","article-title":"Complement and coagulation cascades in trauma","volume":"6","author":"Satyam","year":"2019","journal-title":"Acute Med Surg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/tsaco-2018-000217","article-title":"Early complementopathy predicts the outcomes of patients with trauma","volume":"4","author":"Li","year":"2019","journal-title":"Trauma Surg Acute Care Open"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318256e000","article-title":"Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care","volume":"72","author":"Gentile","year":"2012","journal-title":"J Trauma Acute Care Surg"},{"key":"B18","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.ccm.2008.06.010","article-title":"The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients","volume":"29","author":"Ward","year":"2008","journal-title":"Clin Chest Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2015.52835","article-title":"Current views on the mechanisms of immune responses to trauma and infection","volume":"40","author":"Binkowska","year":"2015","journal-title":"Cent Eur J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2007.10.003","article-title":"Systemic inflammation after trauma","volume":"38","author":"Lenz","year":"2007","journal-title":"Injury"},{"key":"B21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13054-017-1605-5","article-title":"Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism","volume":"21","author":"Johansson","year":"2017","journal-title":"Crit Care"},{"key":"B22","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1097\/SLA.0000000000001751","article-title":"Traumatic endotheliopathy: A prospective observational study of 424 severely injured patients","volume":"265","author":"Johansson","year":"2017","journal-title":"Ann Surg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0212-8","article-title":"The endothelial glycocalyx: composition, functions, and visualization","volume":"454","author":"Reitsma","year":"2007","journal-title":"Pflugers Arch"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3758278","article-title":"The endothelial glycocalyx: New diagnostic and therapeutic approaches in sepsis","volume":"2016","author":"Martin","year":"2016","journal-title":"BioMed Res Int"},{"key":"B25","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1097\/SLA.0b013e318226113d","article-title":"A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein c depletion, fibrinolysis, and increased mortality in trauma patients","volume":"254","author":"Johansson","year":"2011","journal-title":"Ann Surg"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.684852","article-title":"Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia","volume":"116","author":"Rehm","year":"2007","journal-title":"Circulation"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2700.115327","article-title":"Blood levels of histone-complexed DNA fragments are associated with coagulopathy, inflammation and endothelial damage early after trauma","volume":"6","author":"Johansson","year":"2013","journal-title":"J Emerg Trauma Shock"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/1757-7241-20-27","article-title":"High levels of soluble VEGF receptor 1 early after trauma are associated with shock, sympathoadrenal activation, glycocalyx degradation and inflammation in severely injured patients: a prospective study","volume":"20","author":"Ostrowski","year":"2012","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-021-00264-3","article-title":"Trauma-induced coagulopathy","volume":"7","author":"Moore","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000004478","article-title":"Pathophysiological response to trauma-induced coagulopathy: A comprehensive review","volume":"130","author":"Duque","year":"2020","journal-title":"Anesth Analg"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14450","article-title":"Trauma-induced coagulopathy: The past, present, and future","volume":"17","author":"Kornblith","year":"2019","journal-title":"J Thromb Haemost"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000542","article-title":"High d-dimer levels predict a poor outcome in patients with severe trauma, even with high fibrinogen levels on arrival: A multicenter retrospective study","volume":"45","author":"Hayakawa","year":"2016","journal-title":"Shock"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03945.x","article-title":"Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations","volume":"8","author":"Frith","year":"2010","journal-title":"J Thromb Haemost"},{"key":"B34","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.injury.2006.10.003","article-title":"Early coagulopathy in multiple injury: an analysis from the German trauma registry on 8724 patients","volume":"38","author":"Maegele","year":"2007","journal-title":"Injury"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12078","article-title":"The incidence and magnitude of fibrinolytic activation in trauma patients","volume":"11","author":"Raza","year":"2013","journal-title":"J Thromb Haemost"},{"key":"B36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/BF02807969","article-title":"[Current findings in the pathogenesis of the shock process in traumatology]","volume":"14","author":"Schlag","year":"1988","journal-title":"Unfallchirurgie"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903678","article-title":"Molecular intercommunication between the complement and coagulation systems","volume":"185","author":"Amara","year":"2010","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100481","article-title":"Can prehospital \"plasma supplement\" neutralize the systemic storm in severe trauma","volume":"2","author":"Zhao","year":"2021","journal-title":"Cell Rep Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1097\/shk.0b013e3180342439","article-title":"Role of the alternative pathway in the early complement activation following major trauma","volume":"28","author":"Ganter","year":"2007","journal-title":"Shock"},{"key":"B40","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40560-016-0200-1","article-title":"Pathophysiology of trauma-induced coagulopathy: disseminated intravascular coagulation with the fibrinolytic phenotype","volume":"5","author":"Hayakawa","year":"2017","journal-title":"J Intensive Care"},{"key":"B41","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1097\/TA.0000000000000885","article-title":"Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients","volume":"80","author":"Chapman","year":"2016","journal-title":"J Trauma Acute Care Surg"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000161","article-title":"Elevated tissue plasminogen activator and reduced plasminogen activator inhibitor promote hyperfibrinolysis in trauma patients","volume":"41","author":"Cardenas","year":"2014","journal-title":"Shock"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000003029","article-title":"Distinct immunologic endotypes are associated with clinical trajectory after severe blunt trauma and hemorrhagic shock","volume":"90","author":"Brakenridge","year":"2021","journal-title":"J Trauma Acute Care Surg"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.01.014","article-title":"Supplementation with antithrombin III ex vivo optimizes enoxaparin responses in critically injured patients","volume":"187","author":"Cardenas","year":"2020","journal-title":"Thromb Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000001032","article-title":"The military injury severity score (mISS): A better predictor of combat mortality than injury severity score (ISS)","volume":"81","author":"Le","year":"2016","journal-title":"J Trauma Acute Care Surg"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216206","article-title":"Comparison of injury severity scores (ISS) obtained by manual coding versus \"Two-step conversion\" from ICD-9-CM","volume":"14","author":"Abajas-Bustillo","year":"2019","journal-title":"PLoS One"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2005.09.027","article-title":"Relationship between American college of surgeons trauma center designation and mortality in patients with severe trauma (injury severity score > 15)","volume":"202","author":"Demetriades","year":"2006","journal-title":"J Am Coll Surg"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-78952-1_6","article-title":"Interaction between the coagulation and complement system","volume":"632","author":"Amara","year":"2008","journal-title":"Adv Exp Med Biol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12959-018-0174-4","article-title":"TTP-like syndrome: novel concept and molecular pathogenesis of endotheliopathy-associated vascular microthrombotic disease","volume":"16","author":"Chang","year":"2018","journal-title":"Thromb J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12959-020-00231-0","article-title":"Disseminated intravascular coagulation: New identity as endotheliopathy-associated vascular microthrombotic disease based on in vivo hemostasis and endothelial molecular pathogenesis","volume":"18","author":"Chang","year":"2020","journal-title":"Thromb J"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2013.1.656","article-title":"Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective","volume":"2013","author":"Holcomb","year":"2013","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e31825b5c10","article-title":"Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy","volume":"73","author":"Ostrowski","year":"2012","journal-title":"J Trauma Acute Care Surg"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023530","article-title":"Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation","volume":"6","author":"Haywood-Watson","year":"2011","journal-title":"PLoS One"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1211","article-title":"Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function","volume":"5","author":"Fu","year":"2013","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"B55","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12967-015-0481-5","article-title":"Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients","volume":"13","author":"Rahbar","year":"2015","journal-title":"J Transl Med"},{"key":"B56","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1055\/s-0034-1398377","article-title":"Profound endothelial damage predicts impending organ failure and death in sepsis","volume":"41","author":"Johansen","year":"2015","journal-title":"Semin Thromb Hemost"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2017.05.012","article-title":"Syndecan-1: A quantitative marker for the endotheliopathy of trauma","volume":"225","author":"Gonzalez Rodriguez","year":"2017","journal-title":"J Am Coll Surg"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000001373","article-title":"Monitoring of vascular endothelial growth factor and its soluble receptor levels in early trauma","volume":"82","author":"Guo","year":"2017","journal-title":"J Trauma Acute Care Surg"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000944","article-title":"Experimental models of endotheliopathy: Impact of shock severity","volume":"49","author":"Hofmann","year":"2018","journal-title":"Shock"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600420","article-title":"Postischemic gene transfer of soluble flt-1 protects against brain ischemia with marked attenuation of blood-brain barrier permeability","volume":"27","author":"Kumai","year":"2007","journal-title":"J Cereb Blood Flow Metab"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2005.22.353","article-title":"VEGF and VEGF receptor expression after experimental brain contusion in rat","volume":"22","author":"Skold","year":"2005","journal-title":"J Neurotrauma"},{"key":"B62","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s13054-015-0943-4","article-title":"Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction","volume":"19","author":"Bomsztyk","year":"2015","journal-title":"Crit Care"},{"key":"B63","article-title":"Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis","volume":"59","author":"Melincovici","year":"2018","journal-title":"Rom J Morphol Embryol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.03.001","article-title":"The anticoagulant protein c pathway","volume":"579","author":"Dahlback","year":"2005","journal-title":"FEBS Lett"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04589.x","article-title":"High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality","volume":"10","author":"Johansson","year":"2012","journal-title":"J Thromb Haemost"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13486","article-title":"Rationale for the selective administration of tranexamic acid to inhibit fibrinolysis in the severely injured patient","author":"Moore","year":"2016","journal-title":"Transfusion"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1701016","article-title":"Temporal changes in fibrinolysis following injury","volume":"46","author":"Moore","year":"2020","journal-title":"Semin Thromb Hemost"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318232e5ab","article-title":"Clotting factor deficiency in early trauma-associated coagulopathy","volume":"71","author":"Rizoli","year":"2011","journal-title":"J Trauma"},{"key":"B69","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.injury.2010.11.003","article-title":"Early coagulopathy in trauma patients: an on-scene and hospital admission study","volume":"43","author":"Floccard","year":"2012","journal-title":"Injury"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: A new complement activation pathway","volume":"12","author":"Huber-Lang","year":"2006","journal-title":"Nat Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03200.x","article-title":"Activation of mannan-binding lectin-associated serine proteases leads to generation of a fibrin clot","volume":"129","author":"Gulla","year":"2010","journal-title":"Immunology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1097\/SHK.0000000000001709","article-title":"Circulating syndecan-1 and tissue factor pathway inhibitor, biomarkers of endothelial dysfunction, predict mortality in burn patients","volume":"56","author":"Keyloun","year":"2020","journal-title":"Shock"},{"key":"B73","doi-asserted-by":"publisher","first-page":"18367","DOI":"10.1038\/s41598-019-54937-x","article-title":"Syndecan-1 predicts outcome in patients with ST-segment elevation infarction independent from infarct-related myocardial injury","volume":"9","author":"Wernly","year":"2019","journal-title":"Sci Rep"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1038\/s41598-021-81300-w","article-title":"The poor prognosis and influencing factors of high d-dimer levels for COVID-19 patients","volume":"11","author":"He","year":"2021","journal-title":"Sci Rep"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.010","article-title":"Neuroimmunology of traumatic brain injury: Time for a paradigm shift","volume":"95","author":"Jassam","year":"2017","journal-title":"Neuron"},{"key":"B76","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1097\/SHK.0000000000000642","article-title":"Sympathoadrenal activation is associated with acute traumatic coagulopathy and endotheliopathy in isolated brain injury","volume":"46","author":"Di Battista","year":"2016","journal-title":"Shock"},{"key":"B77","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s13049-018-0565-3","article-title":"Traumatic brain injury is associated with increased syndecan-1 shedding in severely injured patients","volume":"26","author":"Gonzalez Rodriguez","year":"2018","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-021-01400-3","article-title":"Extended coagulation profiling in isolated traumatic brain injury: A CENTER-TBI analysis","volume":"36","author":"Bohm","year":"2022","journal-title":"Neurocrit Care"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.06.150","article-title":"Complement analysis in the 21st century","volume":"44","author":"Mollnes","year":"2007","journal-title":"Mol Immunol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00134-020-06266-1","article-title":"Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial","volume":"47","author":"Baksaas-Aasen","year":"2021","journal-title":"Intensive Care Med"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14447","article-title":"Thromboelastography-guided therapy improves patient blood management and certain clinical outcomes in elective cardiac and liver surgery and emergency resuscitation: A systematic review and analysis","volume":"17","author":"Dias","year":"2019","journal-title":"J Thromb Haemost"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0000000000001568","article-title":"Rotational thromboelastometry significantly optimizes transfusion practices for damage control resuscitation in combat casualties","volume":"83","author":"Prat","year":"2017","journal-title":"J Trauma Acute Care Surg"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181d3599c","article-title":"Postinjury coagulopathy management: Goal directed resuscitation via POC thrombelastography","volume":"251","author":"Kashuk","year":"2010","journal-title":"Ann Surg"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e31821e1bf0","article-title":"Rapid thrombelastography delivers real-time results that predict transfusion within 1 hour of admission","volume":"71","author":"Cotton","year":"2011","journal-title":"J Trauma"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1097\/TA.0b013e31824d56ad","article-title":"Admission rapid thrombelastography predicts development of pulmonary embolism in trauma patients","volume":"72","author":"Cotton","year":"2012","journal-title":"J Trauma Acute Care Surg"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.991048\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T12:17:52Z","timestamp":1666268272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.991048\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":85,"alternative-id":["10.3389\/fimmu.2022.991048"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.991048","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]},"article-number":"991048"}}