The Clot Thickens: Sepsis-Induced Coagulopathy Revealed

Check out the timestamps below to help you navigate through the many topics we discussed.

On This Episode:

Today we’re diving deep into a critical and often deadly complication in septic patients: Sepsis-Induced Coagulopathy or SIC. We’ll be discussing the pathophysiology, clinical presentation, diagnosis, and management strategies based on a comprehensive narrative review by Drs. Brittney Williams, Lin Zou, Jean-Francois Pittet, and Wei Chao.

Sepsis is already a significant challenge in critical care, but when it leads to complications like SIC, it becomes even more complex and dangerous. Understanding SIC is crucial for improving patient outcomes. This episode aims to provide a detailed and thorough examination of this condition, highlighting the latest research and clinical insights.

 

Here’s some of what we discuss in this episode:

  • The pathophysiology of SIC is a complex interplay between the immune and coagulation systems.
  • We’ll discuss the diagnostic criteria and tools in detail.
  • Early and accurate diagnosis is essential for initiating appropriate management strategies and improving patient outcomes.
  • Management of SIC involves both supportive care and targeted therapies.
  • Ongoing research is essential to develop more effective diagnostic tools and treatment strategies.

 

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References:

Abraham E, Laterre PF, Garg R, et al.; Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med. 2005;353:1332–1341.

 

Abraham E, Reinhart K, Opal S, et al.; OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003;290:238–247.

 

Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383.

 

Agnew A, Nulty C, Creagh EM. Regulation, activation and function of caspase-11 during health and disease. Int J Mol Sci. 2021;22:1506.

 

Aikawa N, Shimazaki S, Yamamoto Y, et al. Thrombomodulin alfa in the treatment of infectious patients complicated by disseminated intravascular coagulation: subanalysis from the phase 3 trial. Shock. 2011;35:349–354.

 

Asakura H, Suga Y, Yoshida T, et al. Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats. Blood Coagul Fibrinolysis. 2003;14:221–228.

 

Aslam R, Speck ER, Kim M, et al. Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-α production in vivo. Blood. 2006;107:637–641.

 

Bakhtiari K, Meijers JC, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004;32:2416–2421.

 

Bannerman DD, Sathyamoorthy M, Goldblum SE. Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins. J Biol Chem. 1998;273:35371–35380.

 

Bernard GR, Margolis BD, Shanies HM, et al.; Extended Evaluation of Recombinant Human Activated Protein C United States Investigators. Extended evaluation of recombinant human activated protein C United States trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest. 2004;125:2206–2216.

 

Bernard GR, Vincent J-L, Laterre P-F, et al.; Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709.

 

Blair P, Rex S, Vitseva O, et al. Stimulation of toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase. Circ Res. 2009;104:346–354.

 

Bockmeyer CL, Claus RA, Budde U, et al. Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor. Haematologica. 2008;93:137–140.

 

Bhagirath VC, Dwivedi DJ, Liaw PC. Comparison of the proinflammatory and procoagulant properties of nuclear, mitochondrial, and bacterial DNA. Shock. 2015;44:265–271.

 

Brown GT, McIntyre TM. Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich microparticles. J Immunol. 2011;186:5489–5496.

 

Bugge TH, Xiao Q, Kombrinck KW, et al. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA. 1996;93:6258–6263.

 

Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD. Pandemic H1N1 influenza infection and vascular thrombosis. Clin Infect Dis. 2011;52:e14–e17.

 

Chen F, Zou L, Williams B, Chao W. Targeting toll-like receptors in sepsis: from bench to clinical trials. Antioxidants Redox Signal. 2021;35:1324–1339.

 

Chung M-C, Jorgensen SC, Popova TG, Bailey CL, Popov SG. Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax. FEMS Immunol Med Microbiol. 2008;54:309–318.

 

Clark SR, Ma AC, Tavener SA, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13:463–469.

 

Claushuis TA, van Vught LA, Scicluna BP, et al.; Molecular Diagnosis and Risk Stratification of Sepsis Consortium. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood. 2016;127:3062–3072.

 

Collins LV, Hajizadeh S, Holme E, Jonsson IM, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J Leukoc Biol. 2004;75:995–1000.

 

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135:2033–2040.

 

Daudel F, Kessler U, Folly H, Lienert JS, Takala J, Jakob SM. Thromboelastometry for the assessment of coagulation abnormalities in early and established adult sepsis: a prospective cohort study. Crit Care. 2009;13:R42–R42.

 

Delabranche X, Helms J, Meziani F. Immunohaemostasis: a new view on haemostasis during sepsis. Ann Intensive Care. 2017;7:117.

 

Delabranche X, Quenot JP, Lavigne T, et al.; on behalf to the Clinical Research in Intensive Care and Sepsis Network. Early detection of disseminated intravascular coagulation during septic shock: a multicenter prospective study. Crit Care Med. 2016;44:e930–e939.

 

Deng M, Scott MJ, Loughran P, et al. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis. J Immunol. 2013;190:5152–5160.

 

Dhainaut JF, Yan SB, Joyce DE, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. 2004;2:1924–1933.

 

Ding R, Wang Z, Lin Y, Liu B, Zhang Z, Ma X. Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: a retrospective study. Blood Coagul Fibrinolysis. 2018;29:551–558.

 

Di Nisio M, Baudo F, Cosmi B, et al.; Italian Society for Thrombosis and Haemostasis. Diagnosis and treatment of disseminated intravascular coagulation: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res. 2012;129:e177–e184.

 

Dwivedi DJ, Toltl LJ, Swystun LL, et al.; Canadian Critical Care Translational Biology Group. Prognostic utility and characterization of cell-free DNA in patients with severe sepsis. Crit Care. 2012;16:R151.

 

Egorina EM, Sovershaev MA, Olsen JO, Østerud B. Granulocytes do not express but acquire monocyte-derived tissue factor in whole blood: evidence for a direct transfer. Blood. 2008;111:1208–1216.

 

Eisele B, Heinrichs H, Delvos U, et al. Antithrombin III in patients with severe sepsis. Intensive Care Med. 1998;24:663–672.

 

Evavold CL, Ruan J, Tan Y, Xia S, Wu H, Kagan JC. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity. 2018;48:35–44.e6.

 

Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circ Res. 2016;118:1392–1408.

 

Fourrier F, Chopin C, Goudemand J, et al. Septic shock, multiple organ failure, and disseminated intravascular coagulation compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest. 1992;101:816–823.

 

Fuchs TA, Brill A, Duerschmied D, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010;107:15880–15885.

 

Gando S, Iba T, Eguchi Y, et al.; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med. 2006;34:625–631.

 

Gando S, Iba T, Eguchi Y, et al.; Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med. 2006;34:625–631.

 

Goeijenbier M, van Wissen M, van de Weg C, et al. Review: viral infections and mechanisms of thrombosis and bleeding. J Med Virol. 2012;84:1680–1696.

 

Goshua G, Pine AB, Meizlish ML, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020;7:e575–e582.

 

Gould TJ, Vu TT, Swystun LL, et al. Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol. 2014;34:1977–1984.

 

Gralnick HR, Williams SB, Morisato DK. Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets. Blood. 1981;58:387–397.

 

Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol. 2018;38:709–725.

 

Hatada T, Wada H, Nobori T, et al. Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost. 2005;94:975–979.

 

Helms J. Study assessing efficacy of Plasmatherapy in Septic Shock-induced Coagulopathy: Feasibility Study (PlasmaFaisa). Clin Trial. 2020:NCT04580563. Available at: https://clinicaltrials.gov/ct2/show/NCT04580563? term = bleeding+coagulopathy& cond = Sepsis&draw=2 . Accessed March 1, 2022.

 

Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958–965.

 

Hoppensteadt D, Tsuruta K, Cunanan J, et al. Thrombin generation mediators and markers in sepsis-associated coagulopathy and their modulation by recombinant thrombomodulin. Clin Appl Thromb Hemost. 2014;20:129–135.

 

Huang H, Zhu J, Gu L, et al. TLR7 mediates acute respiratory distress syndrome in sepsis by sensing extracellular miR-146a. Am J Respir Cell Mol Biol. 2022;67:375–388.

 

Hyun J, Kim HK, Kim JE, et al. Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation. Thromb Res. 2009;124:75–79.

 

Iba T, Arakawa M, Di Nisio M, et al. Newly proposed sepsis-induced coagulopathy precedes International Society on Thrombosis and Haemostasis overt-disseminated intravascular coagulation and predicts high mortality. J Intensive Care Med. 2018;35.

 

Iba T, Levy JH. Derangement of the endothelial glycocalyx in sepsis. J Thrombosis Haemostasis. 2019;17:283–294.

 

Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017;7:e017046.

 

Iba T, Saito D, Wada H, Asakura H. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012;130:e129–e133.

 

Ince C, Mayeux PR, Nguyen T, et al.; ADQI XIV Workgroup. The endothelium in sepsis. Shock. 2016;45:259–270.

 

Ito T. PAMPs and DAMPs as triggers for DIC. J Intensive Care. 2014;2:67.

 

Ito T, Kawahara K, Nakamura T, et al. High-mobility group box 1 protein promotes development of microvascular thrombosis in rats. J Thromb Haemost. 2007;5:109–116.

 

Ito T, Kakuuchi M, Maruyama I. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation. Crit Care. 2021;25:95.

 

Jesty J, Beltrami E. Positive feedbacks of coagulation. Arterioscler Thromb Vasc Biol. 2005;25:2463–2469.

 

Kannemeier C, Shibamiya A, Nakazawa F, et al. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci U S A. 2007;104:6388–6393.

 

Khakpour S, Wilhelmsen K, Hellman J. Vascular endothelial cell toll-like receptor pathways in sepsis. Innate Immunity. 2015;21:827–846.

 

Kienast J, Juers M, Wiedermann CJ, et al.; KyberSept investigators. Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation. J Thromb Haemost. 2006;4:90–97.

 

Kim JE, Yoo HJ, Gu JY, Kim HK. Histones induce the procoagulant phenotype of endothelial cells through tissue factor up-regulation and thrombomodulin down-regulation. PLoS One. 2016;11:e0156763.

 

Kim S-M, Kim S-I, Yu G, Kim Y-J, Kim WY. Which septic shock patients with non-overt DIC progress to DIC after admission? Point-of-care thromboelastography testing. Shock. 2022;57.

 

Kleinschnitz C, Stoll G, Bendszus M, et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med. 2006;203:513–518.

 

Kobayashi M, Shimada K, Ozawa T. Human recombinant interleukin-1 beta- and tumor necrosis factor alpha-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells. J Cell Physiol. 1990;144:383–390.

 

Kudo D, Goto T, Uchimido R, et al. Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies. Crit Care. 2021;25:114.

 

Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020;395:1517–1520.

 

Li L, Huang L, Huang C, et al. The multiomics landscape of serum exosomes during the development of sepsis. J Adv Res. 2022;39:203–223.

 

Lin S-M, Wang Y-M, Lin H-C, et al. Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis*. Crit Care Med. 2008;36:683–689.

 

López ML, Bruges G, Crespo G, et al. Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing. Thromb Haemost. 2014;112:992–1001.

 

Lund JM, Alexopoulou L, Sato A, et al. Recognition of single-stranded RNA viruses by toll-like receptor 7. Proc

 

Natl Acad Sci USA. 2004;101:5598–5603.

 

Lv B, Wang H, Tang Y, Fan Z, Xiao X, Chen F. High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-kappaB and Egr-1. Thromb Haemost. 2009;102:352–359.

 

Madoiwa S, Nunomiya S, Ono T, et al. Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation. Int J Hematol. 2006;84:398–405.

 

Martinod K, Demers M, Fuchs TA, et al. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A. 2013;110:8674–8679.

 

Matsubara T, Yamakawa K, Umemura Y, et al.; Japanese Association for Acute Medicine (JAAM) Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) Group. Significance of plasma fibrinogen level and antithrombin activity in sepsis: a multicenter cohort study using a cubic spline model. Thromb Res. 2019;181:17–23.

 

Matsumoto H, Yamakawa K, Ogura H, Koh T, Matsumoto N, Shimazu T. Clinical significance of tissue factor and CD13 double-positive microparticles in SIRS patients with trauma and severe sepsis. Shock. 2017;47:409–415.

 

Matsumoto H, Yamakawa K, Ogura H, Koh T, Matsumoto N, Shimazu T. Enhanced expression of cell-specific surface antigens on endothelial microparticles in sepsis-induced disseminated intravascular coagulation. Shock. 2015;43:443–449.

 

McDonald B, Davis RP, Kim S-J, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129:1357–1367.

 

Morrissey J, Drake T. Procoagulant response of the endothelium and monocytes. Pathophysiol Shock Sepsis Organ Fail. 1993:564–574.

 

Müller F, Mutch NJ, Schenk WA, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139:1143–1156.

 

Müller MC, Meijers JCM, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18:R30.

 

Nakahara M, Ito T, Kawahara K, et al. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism. PLoS One. 2013;8:e75961.

 

Nickel KF, Renné T. Crosstalk of the plasma contact system with bacteria. Thromb Res. 2012;130(suppl 1):S78–S83.

 

Nadel S. RESOLVE-ing sepsis in children–not yet! Crit Care. 2007;11:138–138.

 

Panes O, Matus V, Sáez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood. 2007;109:5242–5250.

 

Pawlinski R, Pedersen B, Schabbauer G, et al. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia. Blood. 2004;103:1342–1347.

 

Pawlinski R, Wang JG, Owens AP 3rd, et al. Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice. Blood. 2010;116:806–814.

 

Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45:486–552.

 

Rhodes A, Wort SJ, Thomas H, Collinson P, Bennett ED. Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit Care. 2006;10:R60.

 

Ribeiro LS, Migliari Branco L, Franklin BS. Regulation of innate immune responses by platelets mini review. Front Immunol. 2019;10:1320.

 

Renné T, Pozgajová M, Grüner S, et al. Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med. 2005;202:271–281.

 

Rosen ED, Chan JC, Idusogie E, et al. Mice lacking factor VII develop normally but suffer fatal perinatal bleeding. Nature. 1997;390:290–294.

 

Schmoch T, Möhnle P, Weigand MA, et al.; SepNet–Critical Care Trials Group. The prevalence of sepsis-induced coagulopathy in patients with sepsis––a secondary analysis of two German multicenter randomized controlled trials. Ann Intensive Care. 2023;13:3.

 

Semeraro F, Ammollo CT, Morrissey JH, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118:1952–1961.

 

Shin HS, Xu F, Bagchi A, et al. Bacterial lipoprotein TLR2 agonists broadly modulate endothelial function and coagulation pathways in vitro and in vivo. J Immunol. 2011;186:1119–1130.

 

Simmons J, Pittet J-F. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol. 2015;28:227–236.

 

Stockschlaeder M, Schneppenheim R, Budde U. Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis. 2014;25:206–216.

 

Suen AO, Chen F, Wang S, et al. Extracellular RNA sensing mediates inflammation and organ injury in a murine model of polytrauma. J Immunol. 2023;210:1990–2000.

 

Takemitsu T, Wada H, Hatada T, et al. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemost. 2011;105:40–44.

 

Tanaka C, Tagami T, Kudo S, et al. Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan. Int J Hematol. 2021;114:164–171.

 

Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86:1327–1330.

 

Vanderschueren S, De Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med. 2000;28:1871–1876.

 

Vincent JL, Francois B, Zabolotskikh I, et al.; SCARLET Trial Group. Effect of a recombinant human soluble thrombomodulin on mortality in patients with sepsis-associated coagulopathy: the SCARLET randomized clinical trial. JAMA. 2019;321:1993–2002.

 

Vincent JL, Ramesh MK, Ernest D, et al. A randomized, double-blind, placebo-controlled, phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation. Crit Care Med. 2013;41:2069–2079.

 

Wang JG, Manly D, Kirchhofer D, Pawlinski R, Mackman N. Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic mice. J Thromb Haemost. 2009;7:1092–1098.

 

Wang S, Yang Y, Suen A, et al. Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis. iScience. 2021;24:103441–103441.

 

Wu C, Lu W, Zhang Y, et al. Inflammasome activation triggers blood clotting and host death through pyroptosis. Immunity. 2019;50:1401–1411.e4.

 

Wu Y. Contact pathway of coagulation and inflammation. Thromb J.

 

2015;13:17–17.

 

Xu J, Feng Y, Jeyaram A, Jay SM, Zou L, Chao W. Circulating plasma extracellular vesicles from septic mice induce inflammation via microRNA- and TLR7-dependent mechanisms. J Immunol. 2018;201:3392–3400.

 

Xu J, Zhang X, Pelayo R, et al. Extracellular histones are major mediators of death in sepsis. Nat Med. 2009;15:1318–1321.

 

Xue M, Sun Z, Shao M, et al. Diagnostic and prognostic utility of tissue factor for severe sepsis and sepsis-induced acute lung injury. J Transl Med. 2015;13:172.

 

Yang X, Cheng X, Tang Y, et al. The role of type 1 interferons in coagulation induced by gram-negative bacteria. Blood. 2020;135:1087–1100.

 

Yang X, Cheng X, Tang Y, et al. Bacterial endotoxin activates the coagulation cascade through gasdermin d-dependent phosphatidylserine exposure. Immunity. 2019;51:983–996.e6.

 

Yang X, Li L, Liu J, Lv B, Chen F. Extracellular histones induce tissue factor expression in vascular endothelial cells via TLR and activation of NF-kappaB and AP-1. Thromb Res. 2016;137:211–218.

 

Youn JH, Oh YJ, Kim ES, Choi JE, Shin JS. High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes. J Immunol. 2008;180:5067–5074.

 

Yokoyama Y, Ito T, Yasuda T, et al. Circulating histone H3 levels in septic patients are associated with coagulopathy, multiple organ failure, and death: a single-center observational study. Thromb J. 2019;17:1.

 

Yu M, Wang H, Ding A, et al. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock. 2006;26:174–179.

 

Zhang G, Han J, Welch EJ, et al. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J Immunol. 2009;182:7997–8004.

 

Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020;18:1324–1329.

 

Zhang Y, Meng H, Ma R, et al. Circulating microparticles, blood cells, and endothelium induce procoagulant activity in sepsis through phosphatidylserine exposure. Shock. 2016;45:299–307.

 

Zhang Z, Ohto U, Shibata T, et al. Structural analysis reveals that toll-like receptor 7 is a dual receptor for guanosine and single-stranded RNA. Immunity. 2016;45:737–748.

 

Zhao B, Bowden RA, Stavchansky SA, Bowman PD. Human endothelial cell response to gram-negative lipopolysaccharide assessed with cDNA microarrays. Am J Physiol Cell Physiol. 2001;281:C1587–C1595.

 

Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.

 

Zou L, Feng Y, Xu G, Jian W, Chao W. Splenic RNA and microRNA mimics promote complement factor B production and alternative pathway activation via innate immune signaling. J Immunol. 2016;196:2788–2798.

 

Zou L, He J, Gu L, et al. Brain innate immune response via miRNA-TLR7 sensing in polymicrobial sepsis. Brain Behav Immun. 2022;100:10–24.

 

Williams B, Neder J, Cui P, et al. Toll-like receptors 2 and 7 mediate coagulation activation and coagulopathy in murine sepsis. J Thromb Haemost. 2019;17:1683–1693.

 

Williams B, Zou L, Pittet J-F, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesthesia & Analgesia. 2024;138(4):696-711. doi: 10.1213/ANE.0000000000006888.

 

Yang X, Cheng X, Tang Y, et al. The role of type 1 interferons in coagulation induced by gram-negative bacteria. Blood. 2020;135:1087–1100.

 

Youn JH, Oh YJ, Kim ES, Choi JE, Shin JS. High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes. J Immunol. 2008;180:5067–5074.

 

Yu M, Wang H, Ding A, et al. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock. 2006;26:174–179.

 

Zhang G, Han J, Welch EJ, et al. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J Immunol. 2009;182:7997–8004.

 

Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020;18:1324–1329.

 

Zhang Y, Meng H, Ma R, et al. Circulating microparticles, blood cells, and endothelium induce procoagulant activity in sepsis through phosphatidylserine exposure. Shock. 2016;45:299–307.

 

Zhang Z, Ohto U, Shibata T, et al. Structural analysis reveals that toll-like receptor 7 is a dual receptor for guanosine and single-stranded RNA. Immunity. 2016;45:737–748.

 

Zhao B, Bowden RA, Stavchansky SA, Bowman PD. Human endothelial cell response to gram-negative lipopolysaccharide assessed with cDNA microarrays. Am J Physiol Cell Physiol. 2001;281:C1587–C1595.

 

Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.

 

Zou L, Feng Y, Xu G, Jian W, Chao W. Splenic RNA and microRNA mimics promote complement factor B production and alternative pathway activation via innate immune signaling. J Immunol. 2016;196:2788–2798.

 

Zou L, He J, Gu L, et al. Brain innate immune response via miRNA-TLR7 sensing in polymicrobial sepsis. Brain Behav Immun. 2022;100:10–24.

 

Williams B, Zou L, Pittet J-F, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesthesia & Analgesia. 2024;138(4):696-711. doi: 10.1213/ANE.0000000000006888.

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