nmpЖурнал им. Н.В. Склифосовского «Неотложная медицинская помощь»Russian Sklifosovsky Journal "Emergency Medical Care"2223-90222541-8017“N.V. Sklifosovsky Research Institute for Emergency Medicine”10.23934/2223-9022-2024-13-4-617-630nmp-2003Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSЭндотелиальная дисфункция при травме: патогенез, клиническое значение, диагностика и лечениеEndothelial Dysfunction in Trauma: Pathogenesis, Clinical Significance, Diagnosis and Treatmenthttps://orcid.org/0000-0002-8195-6172МатюхинВ. В.MatyukhinV. V.

Матюхин Виктор Викторович - кандидат медицинских наук, доцент, доцент кафедры госпитальной хирургии.

400131, Волгоград, пл. Павших Борцов, д. 1; 400138, Волгоград, ул. им. Землячки, д. 74

Viktor V. Matyukhin - Candidate of Medical Sciences, Associate Professor, Department of Hospital Surgery.

Pavshikh Bortsov Sq. 1, Volgograd, 400131; Zemlyachki Str. 74, Volgograd, 400138

victor.matyukhin@gmail.comhttps://orcid.org/0000-0002-5275-4213МаскинС. С.MaskinS. S.

Маскин Сергей Сергеевич - доктор медицинских наук, профессор, заведующий кафедрой госпитальной хирургии ФГБОУ ВО ВолгГМУ МЗ РФ.

400131, Волгоград, пл. Павших Борцов, д. 1

Sergey S. Maskin - Doctor of Medical Sciences, Full Professor, Head, Department of Hospital Surgery.

Pavshikh Bortsov Sq. 1, Volgograd, 400131

maskins@bk.ruhttps://orcid.org/0000-0001-8364-8934АлександровВ. В.AleksandrovV. V.

Александров Василий Владимирович - кандидат медицинских наук, доцент кафедры госпитальной хирургии.

400131, Волгоград, пл. Павших Борцов, д. 1

Vasily V. Aleksandrov - Candidate of Medical Sciences, Associate Professor, Department of Hospital Surgery.

Pavshikh Bortsov Sq. 1, Volgograd, 400131

79178304989@yandex.ruhttps://orcid.org/0000-0002-3027-3355ДудченкоГ. П.DudchenkoG. P.

Дудченко Галина Петровна - доктор биологических наук, доцент, профессор кафедры теоретической биохимии с курсом клинической биохимии.

400131, Волгоград, пл. Павших Борцов, д. 1

Galina P. Dudchenko - Doctor of Biological Sciences, Associate Professor, Professor, Department of Theoretical Biochemistry with a Course of Clinical Biochemistry.

Pavshikh Bortsov Sq. 1, Volgograd, 400131

dgalina@mail.ruhttps://orcid.org/0000-0001-9827-9545ОстровскийО. В.OstrovskyO. V.

Островский Олег Владимирович - доктор медицинских наук, профессор, заведующий кафедрой теоретической биохимии с курсом клинической биохимии.

400131, Волгоград, пл. Павших Борцов, д. 1

Oleg V. Ostrovsky - Doctor of Medical Sciences, Full Professor, Head, Department of Theoretical Biochemistry with a Course of Clinical Biochemistry.

Pavshikh Bortsov Sq. 1, Volgograd, 400131

ol.ostr@gmail.comhttps://orcid.org/0000-0002-6313-0908АлимовМ. Н.AlimovM. N.

Алимов Максим Николаевич - врач-хирург хирургического отделения.

400138, Волгоград, ул. им. Землячки, д. 74

Maxim N. Alimov - Surgeon, Surgical Department.

Zemlyachki Str. 74, Volgograd, 400138

qwmajlo@gmail.comhttps://orcid.org/0000-0003-0853-0148ВерлеО. В.WerleO. V.

Верле Ольга Владимировна - ассистент кафедры теоретической биохимии с курсом клинической биохимии.

400131, Волгоград, пл. Павших Борцов, д. 1

Olga V. Werle - Assistant, Department of Theoretical Biochemistry with a Course of Clinical Biochemistry.

Pavshikh Bortsov Sq. 1, Volgograd, 400131

verle_olga@mail.ruФГБОУ ВО «Волгоградский государственный медицинский университет» МЗ РФ; ГУЗ «Городская клиническая больница скорой медицинской помощи № 25»РоссияVolgograd State Medical University; Municipal Clinical Emergency Hospital No. 25Russian FederationФГБОУ ВО «Волгоградский государственный медицинский университет» МЗ РФРоссияVolgograd State Medical UniversityRussian FederationГУЗ «Городская клиническая больница скорой медицинской помощи № 25»РоссияMunicipal Clinical Emergency Hospital No. 25Russian Federation202428012025134617630Copyright © Матюхин В.В., Маскин С.С., Александров В.В., Дудченко Г.П., Островский О.В., Алимов М.Н., Верле О.В., 20252025Матюхин В.В., Маскин С.С., Александров В.В., Дудченко Г.П., Островский О.В., Алимов М.Н., Верле О.В.Matyukhin V.V., Maskin S.S., Aleksandrov V.V., Dudchenko G.P., Ostrovsky O.V., Alimov M.N., Werle O.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jnmp.ru/jour/article/view/2003

Тяжелая травма представляет собой важнейшую медицинскую и социальную проблему. Тяжелые повреждения являются главной причиной гибели людей в возрасте до 44 лет. Многие выжившие после травмы становятся инвалидами. Если не учитывать немедленную смерть пострадавших на догоспитальном этапе, внутрибольничная летальность, как правило, обусловлена геморрагическим шоком, коагулопатией, системным воспалением, как инфекционной, так и неинфекционной природы, и полиорганной недостаточностью.

В последнее десятилетие признается значительная роль эндотелиальной дисфункции в развитии данных патологических процессов. Под эндотелиальной дисфункцией понимают чрезмерную активацию эндотелия, сопровождающуюся мультисистемными проявлениями. В данном обзоре литературы представлены современные данные о физиологии нормального эндотелия, патогенезе развития эндотелиальной дисфункции при травме, о ее роли в развитии системного воспаления, повышения сосудистой проницаемости и коагулопатии, о методах ее диагностики и коррекции.

Severe trauma is a major medical and social problem. Severe injures is the leading cause of death in people under the age of 44. Many trauma survivors become disabled. Apart from immediate death of victims at the prehospital stage, in-hospital mortality is usually due to hemorrhagic shock, coagulopathy, systemic inflammation, both infectious and non-infectious nature, and multiple organ failure. In the last decade, a significant role of endothelial dysfunction in the development of these pathological processes has been recognized. Endothelial dysfunction refers to excessive activation of the endothelium, accompanied by multisystem manifestations. This literature review presents current data on the physiology of normal endothelium, the pathogenesis of endothelial dysfunction in trauma, its role in the development of systemic inflammation, increased vascular permeability and coagulopathy, and methods for its diagnosis and correction.

эндотелийэндотелиальная дисфункцияэндотелиальный гликокаликскоагулопатиясиндекан-1тромбомодулинфактор Виллебрандаплазматранексамовая кислотаendotheliumendothelial dysfunctionendothelial glycocalyxcoagulopathysyndecan-1thrombomodullinvon Willebrand factorplasmatranexamic acidИсследование выполнено за счет финансирования НИР «Роль системного воспаления, эндотелиальной дисфункции и коагулопатии в патогенезе травматической болезни при тяжелой сочетанной травме» из средств ФГБОУ ВО «Волгоградский государственный медицинский университет» МЗ РФ (приказ от №2127-КО 26.12.2022 г.)The study was funded by the research work ˝The role of systemic inflammation, endothelial dysfunction and coagulopathy in the pathogenesis of traumatic disease in severe concomitant trauma˝ from the funds of Volgograd State Medical University (Order No. 2127-KO 26.12.2022)Referencesvan Breugel JMM, Niemeyer MJS, Houwert RM, Groenwold RHH, Leenen LPH, van Wessem KJP. Global changes in mortality rates in polytrauma patients admitted to the ICU-a systematic review. World J Emerg Surg. 2020;15(1):55. PMID: 32998744 https://doi.org/10.1186/s13017-020-00330-3van Breugel JMM, Niemeyer MJS, Houwert RM, Groenwold RHH, Leenen LPH, van Wessem KJP. Global changes in mortality rates in polytrauma patients admitted to the ICU-a systematic review. World J Emerg Surg. 2020;15(1):55. PMID: 32998744 https://doi.org/10.1186/s13017-020-00330-3Sasser SM, Hunt RC, Faul M, Sugerman D, Pearson WS, Dulski T, et al. Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage, 2011. MMWR Recomm Rep. 2012;61(RR–1):1–20. PMID: 22237112Sasser SM, Hunt RC, Faul M, Sugerman D, Pearson WS, Dulski T, et al. Guidelines for field triage of injured patients: recommendations of the National Expert Panel on Field Triage, 2011. MMWR Recomm Rep. 2012;61(RR–1):1–20. PMID: 22237112Cothren CC, Moore EE, Hedegaard HB, Meng K. Epidemiology of urban trauma deaths: a comprehensive reassessment 10 years later. World J Surg. 2007;31(7):1507–1511. PMID: 17505854 https://doi.org/10.1007/s00268-007-9087-2Cothren CC, Moore EE, Hedegaard HB, Meng K. Epidemiology of urban trauma deaths: a comprehensive reassessment 10 years later. World J Surg. 2007;31(7):1507–1511. PMID: 17505854 https://doi.org/10.1007/s00268-007-9087-2Global status report on road safety 2018. Geneva: World Health Organization; 2018.Global status report on road safety 2018. Geneva: World Health Organization; 2018.Weihs V, Frenzel S, Dedeyan M, Hruska F, Staats K, Hajdu S, et al. 25Year experience with adult polytraumatized patients in a European level 1 trauma center: polytrauma between 1995 and 2019. What has changed? A retrospective cohort study. Arch Orthop Trauma Surg. 2023;143(5):2409–2415. PMID: 3541207 https://doi.org/10.1007/s00402-022-04433-1Weihs V, Frenzel S, Dedeyan M, Hruska F, Staats K, Hajdu S, et al. 25Year experience with adult polytraumatized patients in a European level 1 trauma center: polytrauma between 1995 and 2019. What has changed? A retrospective cohort study. Arch Orthop Trauma Surg. 2023;143(5):2409–2415. PMID: 3541207 https://doi.org/10.1007/s00402-022-04433-1WHO Mortality Database. World Health Organization. Available at: https://platform.who.int/mortality/themes/theme-details/MDB/injuries [Accessed Nov 26, 2024]WHO Mortality Database. World Health Organization. Available at: https://platform.who.int/mortality/themes/theme-details/MDB/injuries [Accessed Nov 26, 2024]Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006;60(6 Suppl):S3–11. PMID: 16763478 https://doi.org/10.1097/01.ta.0000199961.02677.19Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006;60(6 Suppl):S3–11. PMID: 16763478 https://doi.org/10.1097/01.ta.0000199961.02677.19Sobrino J, Shafi S. Timing and causes of death after injuries. Proc (Bayl Univ Med Cent). 2013;26(2):120–123. PMID: 23543966 https://doi.org/10.1080/08998280.2013.11928934Sobrino J, Shafi S. Timing and causes of death after injuries. Proc (Bayl Univ Med Cent). 2013;26(2):120–123. PMID: 23543966 https://doi.org/10.1080/08998280.2013.11928934Brohi K, Gruen RL, Holcomb JB. Why are bleeding trauma patients still dying? Intensive Care Med. 2019;45(5):709–711. PMID: 30741331 https://doi.org/10.1007/s00134-019-05560-xBrohi K, Gruen RL, Holcomb JB. Why are bleeding trauma patients still dying? Intensive Care Med. 2019;45(5):709–711. PMID: 30741331 https://doi.org/10.1007/s00134-019-05560-xSchmitt J, Gurney J, Aries P, Danguy Des Deserts M. Advances in trauma care to save lives from traumatic injury: a narrative review. J Trauma Acute Care Surg. 2023;95(2):285–292. PMID: 36941236 https://doi.org/10.1097/TA.0000000000003960Schmitt J, Gurney J, Aries P, Danguy Des Deserts M. Advances in trauma care to save lives from traumatic injury: a narrative review. J Trauma Acute Care Surg. 2023;95(2):285–292. PMID: 36941236 https://doi.org/10.1097/TA.0000000000003960Dobson GP, Morris JL, Letson HL. Why are bleeding trauma patients still dying? Towards a systems hypothesis of trauma. Front Physiol. 2022;13:990903. PMID: 36148305 https://doi.org/10.3389/fphys.2022.990903Dobson GP, Morris JL, Letson HL. Why are bleeding trauma patients still dying? Towards a systems hypothesis of trauma. Front Physiol. 2022;13:990903. PMID: 36148305 https://doi.org/10.3389/fphys.2022.990903Richards JE, Samet RE, Grissom TE. Scratching the Surface: Endothelial Damage in Traumatic Hemorrhagic Shock. Adv Anesth. 2021;39:35–51. PMID: 34715980 https://doi.org/10.1016/j.aan.2021.07.003Richards JE, Samet RE, Grissom TE. Scratching the Surface: Endothelial Damage in Traumatic Hemorrhagic Shock. Adv Anesth. 2021;39:35–51. PMID: 34715980 https://doi.org/10.1016/j.aan.2021.07.003Aird WC. Endothelium as an organ system. Crit Care Med. 2004;32(5 Suppl):S271–279. PMID: 15118530 https://doi.org/10.1097/01.ccm.0000129669.21649.40Aird WC. Endothelium as an organ system. Crit Care Med. 2004;32(5 Suppl):S271–279. PMID: 15118530 https://doi.org/10.1097/01.ccm.0000129669.21649.40Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869–901. PMID: 15269339 https://doi.org/10.1152/physrev.00035.2003Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869–901. PMID: 15269339 https://doi.org/10.1152/physrev.00035.2003Mescher AL. Junqueira’s Basic Histology: Text and Atlas. 14th ed. New York: McGraw-Hill Education; 2016.Mescher AL. Junqueira’s Basic Histology: Text and Atlas. 14th ed. New York: McGraw-Hill Education; 2016.Houston MC. Vascular Biology in Clinical Practice. London: Hanley&Belfus; 2002.Houston MC. Vascular Biology in Clinical Practice. London: Hanley&Belfus; 2002.Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury. Shock. 2016;46(3 Suppl 1):96–103. PMID: 27206278 https://doi.org/10.1097/sHK.0000000000000642Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal Activation is Associated with Acute Traumatic Coagulopathy and Endotheliopathy in Isolated Brain Injury. Shock. 2016;46(3 Suppl 1):96–103. PMID: 27206278 https://doi.org/10.1097/sHK.0000000000000642Johansson PI, Stensballe J, Ostrowski SR. Shock induced endotheliopathy (SHINE) in acute critical illness – a unifying pathophysiologic mechanism. Crit Care. 2017;21(1):25. PMID: 28179016 https://doi.org/10.1186/s13054-017-1605-5Johansson PI, Stensballe J, Ostrowski SR. Shock induced endotheliopathy (SHINE) in acute critical illness – a unifying pathophysiologic mechanism. Crit Care. 2017;21(1):25. PMID: 28179016 https://doi.org/10.1186/s13054-017-1605-5Johansson PI, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Traumatic Endotheliopathy: A Prospective Observational Study of 424 Severely Injured Patients. Ann Surg. 2017;265(3):597–603. PMID: 27144442 https://doi.org/10.1097/SLA.0000000000001751Johansson PI, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Traumatic Endotheliopathy: A Prospective Observational Study of 424 Severely Injured Patients. Ann Surg. 2017;265(3):597–603. PMID: 27144442 https://doi.org/10.1097/SLA.0000000000001751Henriksen HH, Marín de Mas I, Herand H, Krocker J, Wade CE, Johansson PI. Metabolic systems analysis identifies a novel mechanism contributing to shock in patients with endotheliopathy of trauma (EoT) involving thromboxane A2 and LTC4. Matrix Biol Plus. 2022;15:100115. PMID: 35813244 https://doi.org/10.1016/j.mbplus.2022.100115Henriksen HH, Marín de Mas I, Herand H, Krocker J, Wade CE, Johansson PI. Metabolic systems analysis identifies a novel mechanism contributing to shock in patients with endotheliopathy of trauma (EoT) involving thromboxane A2 and LTC4. Matrix Biol Plus. 2022;15:100115. PMID: 35813244 https://doi.org/10.1016/j.mbplus.2022.100115Krocker JD, Lee KH, Henriksen HH, Wang YW, Schoof EM, Karvelsson ST, et al. Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma. Int J Mol Sci. 2022;23(11):6213. PMID: 35682894 https://doi.org/10.3390/ijms23116213Krocker JD, Lee KH, Henriksen HH, Wang YW, Schoof EM, Karvelsson ST, et al. Exploratory Investigation of the Plasma Proteome Associated with the Endotheliopathy of Trauma. Int J Mol Sci. 2022;23(11):6213. PMID: 35682894 https://doi.org/10.3390/ijms23116213Hofmann N, Zipperle J, Jafarmadar M, Ashmwe M, Keibl C, Penzenstadler C, et al. Experimental Models of Endotheliopathy: Impact of Shock Severity. Shock. 2018;49(5):564–571. PMID: 28697004 https://doi.org/10.1097/SHK.0000000000000944Hofmann N, Zipperle J, Jafarmadar M, Ashmwe M, Keibl C, Penzenstadler C, et al. Experimental Models of Endotheliopathy: Impact of Shock Severity. Shock. 2018;49(5):564–571. PMID: 28697004 https://doi.org/10.1097/SHK.0000000000000944Bunch CM, Chang E, Moore EE, Moore HB, Kwaan HC, Miller JB, et al. SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and nontraumatic shock. Front Physiol. 2023;14:1094845 PMID: 36923287 https://doi.org/10.3389/fphys.2023.1094845Bunch CM, Chang E, Moore EE, Moore HB, Kwaan HC, Miller JB, et al. SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and nontraumatic shock. Front Physiol. 2023;14:1094845 PMID: 36923287 https://doi.org/10.3389/fphys.2023.1094845van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228. PMID: 29339798 https://doi.org/10.1038/nrm.2017.125van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–228. PMID: 29339798 https://doi.org/10.1038/nrm.2017.125Zeineddin A, Wu F, Dong JF, Huang H, Zou L, Chao W, et al. TraumaDerived Extracellular Vesicles are Sufficient to Induce Endothelial Dysfunction and Coagulopathy. Shock. 2022;58(1):38–44. PMID: 35984759 https://doi.org/10.1097/SHK.0000000000001950Zeineddin A, Wu F, Dong JF, Huang H, Zou L, Chao W, et al. TraumaDerived Extracellular Vesicles are Sufficient to Induce Endothelial Dysfunction and Coagulopathy. Shock. 2022;58(1):38–44. PMID: 35984759 https://doi.org/10.1097/SHK.0000000000001950Dujardin RWG, Kisters JEC, Wirtz MR, Hajji N, Tuip-de Boer AM, Stensballe J, et al. Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles. Int J Mol Sci. 2022;23(24):15990. PMID: 36555630 https://doi.org/10.3390/ijms232415990Dujardin RWG, Kisters JEC, Wirtz MR, Hajji N, Tuip-de Boer AM, Stensballe J, et al. Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles. Int J Mol Sci. 2022;23(24):15990. PMID: 36555630 https://doi.org/10.3390/ijms232415990Valade G, Libert N, Martinaud C, Vicaut E, Banzet S, Peltzer J. Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock. Front Immunol. 2021;12:749659. PMID: 34659252 https://doi.org/10.3389/fimmu.2021.749659Valade G, Libert N, Martinaud C, Vicaut E, Banzet S, Peltzer J. Therapeutic Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Prevention of Organ Injuries Induced by Traumatic Hemorrhagic Shock. Front Immunol. 2021;12:749659. PMID: 34659252 https://doi.org/10.3389/fimmu.2021.749659Miyazawa B, Trivedi A, Togarrati PP, Potter D, Baimukanova G, Vivona L, et al. Regulation of endothelial cell permeability by platelet-derived extracellular vesicles. J Trauma Acute Care Surg. 2019;86(6):931–942. PMID: 31124890 https://doi.org/10.1097/TA.0000000000002230Miyazawa B, Trivedi A, Togarrati PP, Potter D, Baimukanova G, Vivona L, et al. Regulation of endothelial cell permeability by platelet-derived extracellular vesicles. J Trauma Acute Care Surg. 2019;86(6):931–942. PMID: 31124890 https://doi.org/10.1097/TA.0000000000002230Wade CE, Matijevic N, Wang YW, Rodriguez EG, Lopez E, Ostrowski SR, et al. Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma. Shock. 2019;51(2):180–184. PMID: 29621120 https://doi.org/10.1097/SHK.0000000000001149Wade CE, Matijevic N, Wang YW, Rodriguez EG, Lopez E, Ostrowski SR, et al. Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma. Shock. 2019;51(2):180–184. PMID: 29621120 https://doi.org/10.1097/SHK.0000000000001149Hellenthal KEM, Brabenec L, Wagner N-M. Regulation and Dysregulation of Endothelial Permeability during Systemic Inflammation. Cells. 2022;11(12):1935. PMID: 35741064 https://doi.org/10.3390/cells11121935Hellenthal KEM, Brabenec L, Wagner N-M. Regulation and Dysregulation of Endothelial Permeability during Systemic Inflammation. Cells. 2022;11(12):1935. PMID: 35741064 https://doi.org/10.3390/cells11121935DeBot M, Mitra S, Lutz P, Schaid TR Jr, Stafford P, Hadley JB, et al. Shock Induces Endothelial Permeability After Trauma Through Increased Activation of RhoA GTPase. Shock. 2022;58(6):542–548. PMID: 36548645 https://doi.org/10.1097/SHK.0000000000002008DeBot M, Mitra S, Lutz P, Schaid TR Jr, Stafford P, Hadley JB, et al. Shock Induces Endothelial Permeability After Trauma Through Increased Activation of RhoA GTPase. Shock. 2022;58(6):542–548. PMID: 36548645 https://doi.org/10.1097/SHK.0000000000002008Richter RP, Russell RT, Hu PJ, Uhlich RM, Swain TA, Kerby JD, et al. Plasma Angiopoietin-2/-1 Ratio is Elevated and Angiopoietin-2 Levels Correlate with Plasma Syndecan-1 Following Pediatric Trauma. Shock. 2019;52(3):340–346. PMID: 30289849 https://doi.org/10.1097/sHK.0000000000001267Richter RP, Russell RT, Hu PJ, Uhlich RM, Swain TA, Kerby JD, et al. Plasma Angiopoietin-2/-1 Ratio is Elevated and Angiopoietin-2 Levels Correlate with Plasma Syndecan-1 Following Pediatric Trauma. Shock. 2019;52(3):340–346. PMID: 30289849 https://doi.org/10.1097/sHK.0000000000001267Wei S, Kao LS, Wang HE, Chang R, Podbielski J, Holcomb JB, et al. Protocol for a pilot randomized controlled trial comparing plasma with balanced crystalloid resuscitation in surgical and trauma patients with septic shock. Trauma Surg Acute Care Open. 2018;3(1):e000220. PMID: 30271882 https://doi.org/10.1136/tsaco-2018-000220Wei S, Kao LS, Wang HE, Chang R, Podbielski J, Holcomb JB, et al. Protocol for a pilot randomized controlled trial comparing plasma with balanced crystalloid resuscitation in surgical and trauma patients with septic shock. Trauma Surg Acute Care Open. 2018;3(1):e000220. PMID: 30271882 https://doi.org/10.1136/tsaco-2018-000220Schlömmer C, Meier J. Inflammatory response in trauma patients: are there ways to decrease the inflammatory reaction? Curr Opin Anaesthesiol. 2020;33(2):253–258. PMID: 32049884 https://doi.org/10.1097/ACO.0000000000000842Schlömmer C, Meier J. Inflammatory response in trauma patients: are there ways to decrease the inflammatory reaction? Curr Opin Anaesthesiol. 2020;33(2):253–258. PMID: 32049884 https://doi.org/10.1097/ACO.0000000000000842Dobson GP, Morris JL, Letson HL. Immune dysfunction following severe trauma: A systems failure from the central nervous system to mitochondria. Front Med (Lausanne). 2022;9:968453. PMID: 36111108 https://doi.org/10.3389/fmed.2022.968453Dobson GP, Morris JL, Letson HL. Immune dysfunction following severe trauma: A systems failure from the central nervous system to mitochondria. Front Med (Lausanne). 2022;9:968453. PMID: 36111108 https://doi.org/10.3389/fmed.2022.968453Hunt BJ,Jurd KM.Endothelialcellactivation.Acentral pathophysiological process. BMJ. 1998;316(7141):1328–1329. PMID: 9563977 https://doi.org/10.1136/bmj.316.7141.1328Hunt BJ,Jurd KM.Endothelialcellactivation.Acentral pathophysiological process. BMJ. 1998;316(7141):1328–1329. PMID: 9563977 https://doi.org/10.1136/bmj.316.7141.1328Fernández-Sarmiento J, Schlapbach LJ, Acevedo L, Santana CR, Acosta Y, Diana A, et al. Endothelial Damage in Sepsis: The Importance of Systems Biology. Front Pediatr. 2022;10:828968. PMID: 35356443 https://doi.org/10.3389/fped.2022.828968Fernández-Sarmiento J, Schlapbach LJ, Acevedo L, Santana CR, Acosta Y, Diana A, et al. Endothelial Damage in Sepsis: The Importance of Systems Biology. Front Pediatr. 2022;10:828968. PMID: 35356443 https://doi.org/10.3389/fped.2022.828968Yang Z, Le TD, Simovic MO, Liu B, Fraker TL, Cancio TS, et al. Traumatized triad of complementopathy, endotheliopathy, and coagulopathy – Impact on clinical outcomes in severe polytrauma patients. Front Immunol. 2022;13:991048. PMID: 36341368 https://doi.org/10.3389/fimmu.2022.991048Yang Z, Le TD, Simovic MO, Liu B, Fraker TL, Cancio TS, et al. Traumatized triad of complementopathy, endotheliopathy, and coagulopathy – Impact on clinical outcomes in severe polytrauma patients. Front Immunol. 2022;13:991048. PMID: 36341368 https://doi.org/10.3389/fimmu.2022.991048Maegele M, Aversa J, Marsee MK, McCauley R, Chitta SH, Vyakaranam S, et al. Changes in Coagulation following Brain Injury. Semin Thromb Hemost. 2020;46(2):155–166. PMID: 32160642 https://doi.org/10.1055/s-0040-1702178Maegele M, Aversa J, Marsee MK, McCauley R, Chitta SH, Vyakaranam S, et al. Changes in Coagulation following Brain Injury. Semin Thromb Hemost. 2020;46(2):155–166. PMID: 32160642 https://doi.org/10.1055/s-0040-1702178White NJ, Ward KR, Pati S, Strandenes G, Cap AP. Hemorrhagic blood failure: Oxygen debt, coagulopathy, and endothelial damage. J Trauma Acute Care Surg. 2017;82(6S Suppl 1):S41–S49. PMID: 28328671 https://doi.org/10.1097/TA.0000000000001436White NJ, Ward KR, Pati S, Strandenes G, Cap AP. Hemorrhagic blood failure: Oxygen debt, coagulopathy, and endothelial damage. J Trauma Acute Care Surg. 2017;82(6S Suppl 1):S41–S49. PMID: 28328671 https://doi.org/10.1097/TA.0000000000001436Petros S. Trauma-Induced Coagulopathy. Hamostaseologie. 2019;39(1):20–27. PMID: 30703820 https://doi.org/10.1055/s-0039-1677853Petros S. Trauma-Induced Coagulopathy. Hamostaseologie. 2019;39(1):20–27. PMID: 30703820 https://doi.org/10.1055/s-0039-1677853Giordano S, Spiezia L, Campello E, Simioni P. The current understanding of trauma-induced coagulopathy (TIC): a focused review on pathophysiology. Intern Emerg Med. 2017;12(7):981–991. PMID: 28477287 https://doi.org/10.1007/s11739-017-1674-0Giordano S, Spiezia L, Campello E, Simioni P. The current understanding of trauma-induced coagulopathy (TIC): a focused review on pathophysiology. Intern Emerg Med. 2017;12(7):981–991. PMID: 28477287 https://doi.org/10.1007/s11739-017-1674-0Ostrowski SR, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients. J Trauma Acute Care Surg. 2017;82(2):293–301. PMID: 27779595 https://doi.org/10.1097/TA.0000000000001304Ostrowski SR, Henriksen HH, Stensballe J, Gybel-Brask M, Cardenas JC, Baer LA, et al. Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients. J Trauma Acute Care Surg. 2017;82(2):293–301. PMID: 27779595 https://doi.org/10.1097/TA.0000000000001304Chang JC. Disseminated intravascular coagulation: is it fact or fancy? Blood Coagul Fibrinolysis. 2018;29(3):330–337. PMID: 29621007 https://doi.org/10.1097/MBC.0000000000000727Chang JC. Disseminated intravascular coagulation: is it fact or fancy? Blood Coagul Fibrinolysis. 2018;29(3):330–337. PMID: 29621007 https://doi.org/10.1097/MBC.0000000000000727Harrington J, Zarzaur BL, Fox EE, Wade CE, Holcomb JB, Savage SA. Variations in clot phenotype following injury: The MA-R ratio and fragile clots. J Trauma Acute Care Surg. 2022;92(3):504–510. PMID: 35196304 https://doi.org/10.1097/TA.0000000000003442Harrington J, Zarzaur BL, Fox EE, Wade CE, Holcomb JB, Savage SA. Variations in clot phenotype following injury: The MA-R ratio and fragile clots. J Trauma Acute Care Surg. 2022;92(3):504–510. PMID: 35196304 https://doi.org/10.1097/TA.0000000000003442Richter RP, Joiner DM, Griffin RL, Jansen JO, Kerby JD, Wade CE, et al. Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study. Ann Surg Open. 2022;3(1): e116. PMID: 35693425 https://doi.org/10.1097/as9.0000000000000116Richter RP, Joiner DM, Griffin RL, Jansen JO, Kerby JD, Wade CE, et al. Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study. Ann Surg Open. 2022;3(1): e116. PMID: 35693425 https://doi.org/10.1097/as9.0000000000000116Johansson PI, Ostrowski SR. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation. Med Hypotheses. 2010;75(6):564–567. PMID: 20708846 https://doi.org/10.1016/j.mehy.2010.07.031Johansson PI, Ostrowski SR. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation. Med Hypotheses. 2010;75(6):564–567. PMID: 20708846 https://doi.org/10.1016/j.mehy.2010.07.031Hahn RG, Patel V, Dull RO. Human glycocalyx shedding: Systematic review and critical appraisal. Acta Anaesthesiol Scand. 2021;65(5):590– 606. PMID: 33595101 https://doi.org/10.1111/aas.13797Hahn RG, Patel V, Dull RO. Human glycocalyx shedding: Systematic review and critical appraisal. Acta Anaesthesiol Scand. 2021;65(5):590– 606. PMID: 33595101 https://doi.org/10.1111/aas.13797Gaudette S, Hughes D, Boller M. The endothelial glycocalyx: Structure and function in health and critical illness. J Vet Emerg Crit Care (San Antonio). 2020;30(2):117–134. PMID: 32067360 https://doi.org/10.1111/ vec.12925Gaudette S, Hughes D, Boller M. The endothelial glycocalyx: Structure and function in health and critical illness. J Vet Emerg Crit Care (San Antonio). 2020;30(2):117–134. PMID: 32067360 https://doi.org/10.1111/vec.12925Patterson EK,Cepinskas G,Fraser DD.Endothelial Glycocalyx Degradation in Critical Illness and Injury. Front Med (Lausanne). 2022;9:898592. PMID: 35872762 https://doi.org/10.3389/fmed.2022.898592Patterson EK,Cepinskas G,Fraser DD.Endothelial Glycocalyx Degradation in Critical Illness and Injury. Front Med (Lausanne). 2022;9:898592. PMID: 35872762 https://doi.org/10.3389/fmed.2022.898592Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, et al. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015;13:117. PMID: 25889764 https://doi.org/10.1186/s12967-015-0481-5Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, et al. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015;13:117. PMID: 25889764 https://doi.org/10.1186/s12967-015-0481-5Wallen TE, Singer KE, Elson NC, Baucom MR, England LG, Schuster RM, et al. Defining Endotheliopathy in Murine Polytrauma Models. Shock. 2022;57(6):291–298. PMID: 35759308 https://doi.org/10.1097/sHK.0000000000001940Wallen TE, Singer KE, Elson NC, Baucom MR, England LG, Schuster RM, et al. Defining Endotheliopathy in Murine Polytrauma Models. Shock. 2022;57(6):291–298. PMID: 35759308 https://doi.org/10.1097/sHK.0000000000001940Suzuki K, Okada H, Sumi K, Tomita H, Kobayashi R, Ishihara T, et al. Syndecan-1 as a severity biomarker for patients with trauma. Front Med (Lausanne). 2022;9:985955. PMID: 36237551 https://doi.org/10.3389/fmed.2022.985955Suzuki K, Okada H, Sumi K, Tomita H, Kobayashi R, Ishihara T, et al. Syndecan-1 as a severity biomarker for patients with trauma. Front Med (Lausanne). 2022;9:985955. PMID: 36237551 https://doi.org/10.3389/fmed.2022.985955Wade CE, Matijevic N, Wang YW, Rodriguez EG, Lopez E, Ostrowski SR, et al. Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma. Shock. 2019;51(2):180–184. PMID: 29621120 https://doi.org/10.1097/SHK.0000000000001149Wade CE, Matijevic N, Wang YW, Rodriguez EG, Lopez E, Ostrowski SR, et al. Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma. Shock. 2019;51(2):180–184. PMID: 29621120 https://doi.org/10.1097/SHK.0000000000001149Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. 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. Ann Surg. 2011;254(2):194–200. PMID: 21772125 https://doi.org/10.1097/SLA.0b013e318226113dJohansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. 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. Ann Surg. 2011;254(2):194–200. PMID: 21772125 https://doi.org/10.1097/SLA.0b013e318226113dAlbert V, Subramanian A, Agrawal D, Pati HP, Gupta SD, Mukhopadhyay AK, et al. Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome. Med Sci (Basel). 2018;6(1):5. PMID: 29337920 https://doi.org/10.3390/medsci6010005Albert V, Subramanian A, Agrawal D, Pati HP, Gupta SD, Mukhopadhyay AK, et al. Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome. Med Sci (Basel). 2018;6(1):5. PMID: 29337920 https://doi.org/10.3390/medsci6010005Gonzalez Rodriguez E, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, et al. Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. J Am Coll Surg. 2017;225(3):419–427. PMID: 28579548 https://doi.org/10.1016/j.jamcollsurg.2017.05.012Gonzalez Rodriguez E, Ostrowski SR, Cardenas JC, Baer LA, Tomasek JS, Henriksen HH, et al. Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma. J Am Coll Surg. 2017;225(3):419–427. PMID: 28579548 https://doi.org/10.1016/j.jamcollsurg.2017.05.012Wei S, Gonzalez Rodriguez E, Chang R, Holcomb JB, Kao LS, Wade CE, et al. Elevated Syndecan-1 after Trauma and Risk of Sepsis: A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial. J Am Coll Surg. 2018;227(6):587–595. PMID: 30243993 https://doi.org/10.1016/j.jamcollsurg.2018.09.003Wei S, Gonzalez Rodriguez E, Chang R, Holcomb JB, Kao LS, Wade CE, et al. Elevated Syndecan-1 after Trauma and Risk of Sepsis: A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial. J Am Coll Surg. 2018;227(6):587–595. PMID: 30243993 https://doi.org/10.1016/j.jamcollsurg.2018.09.003Henriksen HH,McGarrity S,SigurÐardóttir RS,Nemkov T,D’Alessandro A, Palsson BO, et al. Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm. Ann Surg. 2020;272(6):1140–1148. PMID: 31274658 https://doi.org/10.1097/sLA.0000000000003307Henriksen HH,McGarrity S,SigurÐardóttir RS,Nemkov T,D’Alessandro A, Palsson BO, et al. Metabolic Systems Analysis of Shock-Induced Endotheliopathy (SHINE) in Trauma: A New Research Paradigm. Ann Surg. 2020;272(6):1140–1148. PMID: 31274658 https://doi.org/10.1097/sLA.0000000000003307Henriksen HH, Marín de Mas I, Nielsen LK, Krocker J, Stensballe J, Karvelsson ST, et al. Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients. Int J Mol Sci. 2023;24(3):2257. PMID: 36768579 https://doi.org/10.3390/ijms24032257Henriksen HH, Marín de Mas I, Nielsen LK, Krocker J, Stensballe J, Karvelsson ST, et al. Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients. Int J Mol Sci. 2023;24(3):2257. PMID: 36768579 https://doi.org/10.3390/ijms24032257Watanabe-Kusunoki K, Nakazawa D, Ishizu A, Atsumi T. Thrombomodulin as a Physiological Modulator of Intravascular Injury. Front Immunol. 2020;11:575890. PMID: 33042158 https://doi.org/10.3389/fimmu.2020.575890Watanabe-Kusunoki K, Nakazawa D, Ishizu A, Atsumi T. Thrombomodulin as a Physiological Modulator of Intravascular Injury. Front Immunol. 2020;11:575890. PMID: 33042158 https://doi.org/10.3389/fimmu.2020.575890Britten MW, Lümers L, Tominaga K, Peters J, Dirkmann D. Glycocalyx components affect platelet function, whole blood coagulation, and fibrinolysis: an in vitro study suggesting a link to trauma-induced coagulopathy. BMC Anesthesiol. 2021;21(1):83. PMID: 33740916 https://doi.org/10.1186/s12871-021-01300-1Britten MW, Lümers L, Tominaga K, Peters J, Dirkmann D. Glycocalyx components affect platelet function, whole blood coagulation, and fibrinolysis: an in vitro study suggesting a link to trauma-induced coagulopathy. BMC Anesthesiol. 2021;21(1):83. PMID: 33740916 https://doi.org/10.1186/s12871-021-01300-1Kudo D, Goto T, Uchimido R, Hayakawa M, Yamakawa K, Abe T, et al. Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies. Crit Care. 2021;25(1):114. PMID: 33741010 https://doi.org/10.1186/s13054-021-03541-5Kudo D, Goto T, Uchimido R, Hayakawa M, Yamakawa K, Abe T, et al. Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies. Crit Care. 2021;25(1):114. PMID: 33741010 https://doi.org/10.1186/s13054-021-03541-5Kregel HR, Hatton GE, Isbell KD, Henriksen HH, Stensballe J, Johansson PI, et al. Shock-Induced Endothelial Dysfunction is Present in Patients with Occult Hypoperfusion After Trauma. Shock. 2022;57(1):106–112. PMID: 34905531 https://doi.org/10.1097/SHK.0000000000001866Kregel HR, Hatton GE, Isbell KD, Henriksen HH, Stensballe J, Johansson PI, et al. Shock-Induced Endothelial Dysfunction is Present in Patients with Occult Hypoperfusion After Trauma. Shock. 2022;57(1):106–112. PMID: 34905531 https://doi.org/10.1097/SHK.0000000000001866Hatton GE, Isbell KD, Henriksen HH, Stensballe J, Brummerstedt M, Johansson PI, et al. Endothelial Dysfunction is Associated with Increased Incidence, Worsened Severity, and Prolonged Duration of Acute Kidney Injury After Severe Trauma. Shock. 2021;55(3):311–315. PMID: 32826819 https://doi.org/10.1097/SHK.0000000000001638Hatton GE, Isbell KD, Henriksen HH, Stensballe J, Brummerstedt M, Johansson PI, et al. Endothelial Dysfunction is Associated with Increased Incidence, Worsened Severity, and Prolonged Duration of Acute Kidney Injury After Severe Trauma. Shock. 2021;55(3):311–315. PMID: 32826819 https://doi.org/10.1097/SHK.0000000000001638Xu X, Kozar R, Zhang J, Dong J-F. Diverse activities of von Willebrand factor in traumatic brain injury and associated coagulopathy. J Thromb Haemost. 2020;18(12):3154–3162. PMID: 32931638 https://doi.org/10.1111/jth.15096Xu X, Kozar R, Zhang J, Dong J-F. Diverse activities of von Willebrand factor in traumatic brain injury and associated coagulopathy. J Thromb Haemost. 2020;18(12):3154–3162. PMID: 32931638 https://doi.org/10.1111/jth.15096Goncharov NV, Nadeev AD, Jenkins RO, Avdonin PV. Markers and Biomarkers of Endothelium: When Something Is Rotten in the State. Oxid Med Cell Longev. 2017;2017:9759735. PMID: 29333215 https://doi.org/10.1155/2017/9759735Goncharov NV, Nadeev AD, Jenkins RO, Avdonin PV. Markers and Biomarkers of Endothelium: When Something Is Rotten in the State. Oxid Med Cell Longev. 2017;2017:9759735. PMID: 29333215 https://doi.org/10.1155/2017/9759735Zeineddin A, Dong JF, Wu F, Terse P, Kozar RA. Role of Von Willebrand Factor after Injury: It May Do More Than We Think. Shock. 2021;55(6):717–722. PMID: 33156241 https://doi.org/10.1097/sHK.0000000000001690Zeineddin A, Dong JF, Wu F, Terse P, Kozar RA. Role of Von Willebrand Factor after Injury: It May Do More Than We Think. Shock. 2021;55(6):717–722. PMID: 33156241 https://doi.org/10.1097/sHK.0000000000001690Naumann DN, Hazeldine J, Midwinter MJ, Hutchings SD, Harrison P. Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock. J Trauma Acute Care Surg. 2018;84(1):81–88. PMID: 28885470 https://doi.org/10.1097/TA.0000000000001695Naumann DN, Hazeldine J, Midwinter MJ, Hutchings SD, Harrison P. Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock. J Trauma Acute Care Surg. 2018;84(1):81–88. PMID: 28885470 https://doi.org/10.1097/TA.0000000000001695Cusack R, Leone M, Rodriguez AH, Martin-Loeches I. Endothelial Damage and the Microcirculation in Critical Illness. Biomedicines. 2022;10(12):3150. PMID: 36551905 https://doi.org/10.3390/biomedicines10123150Cusack R, Leone M, Rodriguez AH, Martin-Loeches I. Endothelial Damage and the Microcirculation in Critical Illness. Biomedicines. 2022;10(12):3150. PMID: 36551905 https://doi.org/10.3390/biomedicines10123150Naumann DN, Hazeldine J, Dinsdale RJ, Bishop JR, Midwinter MJ, Harrison P, et al. Endotheliopathy is associated with higher levels of cell-free DNA following major trauma: A prospective observational study. PLoS One. 2017;12(12):e0189870. PMID: 29261771 https://doi.org/10.1371/journal.pone.0189870Naumann DN, Hazeldine J, Dinsdale RJ, Bishop JR, Midwinter MJ, Harrison P, et al. Endotheliopathy is associated with higher levels of cell-free DNA following major trauma: A prospective observational study. PLoS One. 2017;12(12):e0189870. PMID: 29261771 https://doi.org/10.1371/journal.pone.0189870Gonzalez Rodriguez E, Cardenas JC, Lopez E, Cotton BA, Tomasek JS, OstrowskiSR,etal.Early IdentificationofthePatientwith Endotheliopathy of Trauma by Arrival Serum Albumin. Shock. 2018;50(1):31–37. PMID: 29049135 https://doi.org/10.1097/SHK.0000000000001036Gonzalez Rodriguez E, Cardenas JC, Lopez E, Cotton BA, Tomasek JS, OstrowskiSR,etal.Early IdentificationofthePatientwith Endotheliopathy of Trauma by Arrival Serum Albumin. Shock. 2018;50(1):31–37. PMID: 29049135 https://doi.org/10.1097/SHK.0000000000001036Torres LN, Chung KK, Salgado CL, Dubick MA, Torres Filho IP. Lowvolume resuscitation with normal saline is associated with microvascular endothelial dysfunction after hemorrhage in rats, compared to colloids and balanced crystalloids. Crit Care. 2017;21(1):160. PMID: 28659186 https://doi.org/10.1186/s13054-017-1745-7Torres LN, Chung KK, Salgado CL, Dubick MA, Torres Filho IP. Lowvolume resuscitation with normal saline is associated with microvascular endothelial dysfunction after hemorrhage in rats, compared to colloids and balanced crystalloids. Crit Care. 2017;21(1):160. PMID: 28659186 https://doi.org/10.1186/s13054-017-1745-7Chi Y, Jiang X, Chai J, Chang Y, Liu T, Liu X, et al. Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock. Ann Transl Med. 2022;10(4):177. PMID: 35280352 https://doi.org/10.21037/atm-21-7004Chi Y, Jiang X, Chai J, Chang Y, Liu T, Liu X, et al. Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock. Ann Transl Med. 2022;10(4):177. PMID: 35280352 https://doi.org/10.21037/atm-21-7004Barry M, Trivedi A, Vivona LR, Chui J, Pathipati P, Miyazawa B, Pati S. Recovery of Endotheliopathy at 24 Hours in an Established Mouse Model of Hemorrhagic Shock and Trauma. Shock. 2022;58(4):313–320. PMID: 36256627 https://doi.org/10.1097/SHK.0000000000001984Barry M, Trivedi A, Vivona LR, Chui J, Pathipati P, Miyazawa B, Pati S. Recovery of Endotheliopathy at 24 Hours in an Established Mouse Model of Hemorrhagic Shock and Trauma. Shock. 2022;58(4):313–320. PMID: 36256627 https://doi.org/10.1097/SHK.0000000000001984Barry M, Pati S. Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation. Matrix Biol Plus. 2022;14:100107. PMID: 35392184 https://doi.org/10.1016/j.mbplus.2022.100107Barry M, Pati S. Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation. Matrix Biol Plus. 2022;14:100107. PMID: 35392184 https://doi.org/10.1016/j.mbplus.2022.100107Baucom MR, Wallen TE, Ammann AM, England LG, Schuster RM, Pritts TA, et al. Blood component resuscitative strategies to mitigate endotheliopathy in a murine hemorrhagic shock model. J Trauma Acute Care Surg. 2023;95(1):21–29. PMID: 37012625 https://doi.org/10.1097/TA.0000000000003942Baucom MR, Wallen TE, Ammann AM, England LG, Schuster RM, Pritts TA, et al. Blood component resuscitative strategies to mitigate endotheliopathy in a murine hemorrhagic shock model. J Trauma Acute Care Surg. 2023;95(1):21–29. PMID: 37012625 https://doi.org/10.1097/TA.0000000000003942Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: Factor concentrate versus fresh frozen plasma. J Trauma Acute Care Surg. 2016;80(4):576–584. PMID: 26808040 https://doi.org/10.1097/TA.0000000000000961Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: Factor concentrate versus fresh frozen plasma. J Trauma Acute Care Surg. 2016;80(4):576–584. PMID: 26808040 https://doi.org/10.1097/TA.0000000000000961Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011;6(8):e23530. PMID: 21886795 https://doi.org/10.1371/journal.pone.0023530Haywood-Watson RJ, Holcomb JB, Gonzalez EA, Peng Z, Pati S, Park PW, et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011;6(8):e23530. PMID: 21886795 https://doi.org/10.1371/journal.pone.0023530Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon’s perspective. Hematology Am Soc Hematol Educ Program. 2013;2013:656–659. PMID: 24319247 https://doi.org/10.1182/asheducation-2013.1.656Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon’s perspective. Hematology Am Soc Hematol Educ Program. 2013;2013:656–659. PMID: 24319247 https://doi.org/10.1182/asheducation-2013.1.656Wu F, Chipman A, Pati S, Miyasawa B, Corash L, Kozar RA. Resuscitative Strategies to Modulate the Endotheliopathy of Trauma: From Cell to Patient. Shock. 2020;53(5):575–584. PMID: 31090680 https://doi.org/10.1097/SHK.0000000000001378Wu F, Chipman A, Pati S, Miyasawa B, Corash L, Kozar RA. Resuscitative Strategies to Modulate the Endotheliopathy of Trauma: From Cell to Patient. Shock. 2020;53(5):575–584. PMID: 31090680 https://doi.org/10.1097/SHK.0000000000001378Peng HT, Nascimento B, Rhind SG, da Luz L, Beckett A. Evaluation of trauma-induced coagulopathy in the fibrinogen in the initial resuscitation of severe trauma trial. Transfusion. 2021;61 (Suppl 1): S49–S57. PMID: 34269460 https://doi.org/10.1111/trf.16488Peng HT, Nascimento B, Rhind SG, da Luz L, Beckett A. Evaluation of trauma-induced coagulopathy in the fibrinogen in the initial resuscitation of severe trauma trial. Transfusion. 2021;61 (Suppl 1): S49–S57. PMID: 34269460 https://doi.org/10.1111/trf.16488Chipman AM, Wu F, Kozar RA. Fibrinogen inhibits microRNA-19b, a novel mechanism for repair of haemorrhagic shock-induced endothelial cell dysfunction. Blood Transfus. 2021;19(5):420–427. PMID: 33539284 https://doi.org/10.2450/2021.0361-20Chipman AM, Wu F, Kozar RA. Fibrinogen inhibits microRNA-19b, a novel mechanism for repair of haemorrhagic shock-induced endothelial cell dysfunction. Blood Transfus. 2021;19(5):420–427. PMID: 33539284 https://doi.org/10.2450/2021.0361-20Diebel LN, Liberati DM, Hla T, Steven Swendeman S. Plasma components to protect the endothelial barrier after shock: A role for sphingosine 1phosphate. Surgery. 2022;171(3):825–832. PMID: 34865862 https://doi.org/10.1016/j.surg.2021.08.068Diebel LN, Liberati DM, Hla T, Steven Swendeman S. Plasma components to protect the endothelial barrier after shock: A role for sphingosine 1phosphate. Surgery. 2022;171(3):825–832. PMID: 34865862 https://doi.org/10.1016/j.surg.2021.08.068Barry M, Trivedi A, Miyazawa BY, Vivona LR, Khakoo M, Zhang H, et al. Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2021;90(6):1022–1031. PMID: 33797484 https://doi.org/10.1097/TA.0000000000003164Barry M, Trivedi A, Miyazawa BY, Vivona LR, Khakoo M, Zhang H, et al. Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2021;90(6):1022–1031. PMID: 33797484 https://doi.org/10.1097/TA.0000000000003164Schaid TR Jr, Hansen KC, Sauaia A, Moore EE, DeBot M, Cralley AL, et al. Postinjury complement C4 activation is associated with adverse outcomes and is potentially influenced by plasma resuscitation. J Trauma Acute Care Surg. 2022;93(5):588–596. PMID: 35610738 https://doi.org/10.1097/TA.0000000000003713Schaid TR Jr, Hansen KC, Sauaia A, Moore EE, DeBot M, Cralley AL, et al. Postinjury complement C4 activation is associated with adverse outcomes and is potentially influenced by plasma resuscitation. J Trauma Acute Care Surg. 2022;93(5):588–596. PMID: 35610738 https://doi.org/10.1097/TA.0000000000003713Hegde S, Zheng Y, Cancelas JA. Novel blood derived hemostatic agents for bleeding therapy and prophylaxis. Curr Opin Hematol. 2022;29(6):281–289. PMID: 35942861 https://doi.org/10.1097/MOH.0000000000000737Hegde S, Zheng Y, Cancelas JA. Novel blood derived hemostatic agents for bleeding therapy and prophylaxis. Curr Opin Hematol. 2022;29(6):281–289. PMID: 35942861 https://doi.org/10.1097/MOH.0000000000000737Stensballe J, Ulrich AG, Nilsson JC, Henriksen HH, Olsen PS, Ostrowski SR, et al. Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial. Anesth Analg. 2018;127(4):920–927. PMID: 29863610 https://doi.org/10.1213/ANE.0000000000003545Stensballe J, Ulrich AG, Nilsson JC, Henriksen HH, Olsen PS, Ostrowski SR, et al. Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial. Anesth Analg. 2018;127(4):920–927. PMID: 29863610 https://doi.org/10.1213/ANE.0000000000003545Trivedi A, Potter DR, Miyazawa BY, Lin M, Vivona LR, Khakoo MA, et al. Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock. J Trauma Acute Care Surg. 2021;90(2):203–214. PMID: 33060537 https://doi.org/10.1097/TA.0000000000002984Trivedi A, Potter DR, Miyazawa BY, Lin M, Vivona LR, Khakoo MA, et al. Freeze-dried platelets promote clot formation, attenuate endothelial cell permeability, and decrease pulmonary vascular leak in a murine model of hemorrhagic shock. J Trauma Acute Care Surg. 2021;90(2):203–214. PMID: 33060537 https://doi.org/10.1097/TA.0000000000002984Diebel LN, Martin JV, Liberati DM. Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model. J Trauma Acute Care Surg. 2017;82(6):1080–1086. PMID: 28328682 https://doi.org/10.1097/TA.0000000000001445Diebel LN, Martin JV, Liberati DM. Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model. J Trauma Acute Care Surg. 2017;82(6):1080–1086. PMID: 28328682 https://doi.org/10.1097/TA.0000000000001445Prudovsky I, Carter D, Kacer D, Palmeri M, Soul T, Kumpel C, et al. Tranexamic acid suppresses the release of mitochondrial DNA, protects the endothelial monolayer and enhances oxidative phosphorylation. J Cell Physiol. 2019;234(11):19121–19129. PMID: 30941770 https://doi.org/10.1002/jcp.28603Prudovsky I, Carter D, Kacer D, Palmeri M, Soul T, Kumpel C, et al. Tranexamic acid suppresses the release of mitochondrial DNA, protects the endothelial monolayer and enhances oxidative phosphorylation. J Cell Physiol. 2019;234(11):19121–19129. PMID: 30941770 https://doi.org/10.1002/jcp.28603Anderson TN, Hinson HE, Dewey EN, Rick EA, Schreiber MA, Rowell SE. Early Tranexamic Acid Administration After Traumatic Brain Injury Is Associated with Reduced Syndecan-1 and Angiopoietin-2 in Patients with Traumatic Intracranial Hemorrhage. J Head Trauma Rehabil. 2020;35(5):317–323. PMID: 32881765 https://doi.org/10.1097/HTR.0000000000000619Anderson TN, Hinson HE, Dewey EN, Rick EA, Schreiber MA, Rowell SE. Early Tranexamic Acid Administration After Traumatic Brain Injury Is Associated with Reduced Syndecan-1 and Angiopoietin-2 in Patients with Traumatic Intracranial Hemorrhage. J Head Trauma Rehabil. 2020;35(5):317–323. PMID: 32881765 https://doi.org/10.1097/HTR.0000000000000619Naumann DN, Hazeldine J, Davies DJ, Bishop J, Midwinter MJ, Belli A, et al. Endotheliopathy of Trauma is an on-Scene Phenomenon, and is Associated with Multiple Organ Dysfunction Syndrome: A Prospective Observational Study. Shock. 2018;49(4):420–428. PMID: 28945676 https://doi.org/10.1097/SHK.0000000000000999Naumann DN, Hazeldine J, Davies DJ, Bishop J, Midwinter MJ, Belli A, et al. Endotheliopathy of Trauma is an on-Scene Phenomenon, and is Associated with Multiple Organ Dysfunction Syndrome: A Prospective Observational Study. Shock. 2018;49(4):420–428. PMID: 28945676 https://doi.org/10.1097/SHK.0000000000000999Diebel LN, Wheaton M, Liberati DM. The protective role of estrogen on endothelial and glycocalyx barriers after shock conditions: A microfluidic study. Surgery. 2021;169(3):678–685. PMID: 32988619 https://doi.org/10.1016/j.surg.2020.08.006Diebel LN, Wheaton M, Liberati DM. The protective role of estrogen on endothelial and glycocalyx barriers after shock conditions: A microfluidic study. Surgery. 2021;169(3):678–685. PMID: 32988619 https://doi.org/10.1016/j.surg.2020.08.006Johansson PI, Eriksen CF, Schmal H, Gaarder C, Pall M, Henriksen HH, et al. Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shinetrauma trial. Acta Anaesthesiol Scand. 2021;65(4):551–557. PMID: 33393084 https://doi.org/10.1111/aas.13776Johansson PI, Eriksen CF, Schmal H, Gaarder C, Pall M, Henriksen HH, et al. Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shinetrauma trial. Acta Anaesthesiol Scand. 2021;65(4):551–557. PMID: 33393084 https://doi.org/10.1111/aas.13776

The authors declare that there are no conflicts of interest present.