CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(11): 1017-1033
DOI: 10.1055/a-2091-7006
Review Article

Monocyte Tissue Factor Expression: Lipopolysaccharide Induction and Roles in Pathological Activation of Coagulation

Ana T. A. Sachetto
1   Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Nigel Mackman
1   Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
› Author Affiliations
Funding This work was supported by the NIH NHLBI R35HL155657 (N.M) and the John C. Parker professorship (N.M).


The coagulation system is a part of the mammalian host defense system. Pathogens and pathogen components, such as bacterial lipopolysaccharide (LPS), induce tissue factor (TF) expression in circulating monocytes that then activates the coagulation protease cascade. Formation of a clot limits dissemination of pathogens, enhances the recruitment of immune cells, and facilitates killing of pathogens. However, excessive activation of coagulation can lead to thrombosis. Here, we review studies on the mechanism of LPS induction of TF expression in monocytes and its contribution to thrombosis and disseminated intravascular coagulation. Binding of LPS to Toll-like receptor 4 on monocytes induces a transient expression of TF that involves activation of intracellular signaling pathways and binding of various transcription factors, such as c-rel/p65 and c-Fos/c-Jun, to the TF promoter. Inhibition of TF in endotoxemia and sepsis models reduces activation of coagulation and improves survival. Studies with endotoxemic mice showed that hematopoietic cells and myeloid cells play major roles in the activation of coagulation. Monocyte TF expression is also increased after surgery. Activated monocytes release TF-positive extracellular vesicles (EVs) and levels of circulating TF-positive EVs are increased in endotoxemic mice and in patients with sepsis. More recently, it was shown that inflammasomes contribute to the induction of TF expression and activation of coagulation in endotoxemic mice. Taken together, these studies indicate that monocyte TF plays a major role in activation of coagulation. Selective inhibition of monocyte TF expression may reduce pathologic activation of coagulation in sepsis and other diseases without affecting hemostasis.

Authors' Contribution

A.T.A.S. and N.M. wrote and edited the manuscript. All the authors read and approved the final manuscript.

Publication History

Received: 03 September 2021

Accepted: 08 May 2023

Accepted Manuscript online:
11 May 2023

Article published online:
19 June 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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  • References

  • 1 Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent J-L. Sepsis and septic shock. Nat Rev Dis Primers 2016; 2 (01) 16045
  • 2 Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR. Pattern recognition receptors and the host cell death molecular machinery. Front Immunol 2018; 9: 2379
  • 3 Loof TG, Schmidt O, Herwald H, Theopold U. Coagulation systems of invertebrates and vertebrates and their roles in innate immunity: the same side of two coins?. J Innate Immun 2011; 3 (01) 34-40
  • 4 Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine 2008; 42 (02) 145-151
  • 5 Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13 (01) 34-45
  • 6 Kawabata S, Muta T. Sadaaki Iwanaga: discovery of the lipopolysaccharide- and beta-1,3-D-glucan-mediated proteolytic cascade and unique proteins in invertebrate immunity. J Biochem 2010; 147 (05) 611-618
  • 7 Howell W. Observations on the Chemical Composition and Coagulation of the Blood of Limulus polyphemus. John Hopkins Univ Circular V. 1885. 5. 4-5
  • 8 Levin J, Bang FB. Clottable protein in Limulus; its localization and kinetics of its coagulation by endotoxin. Thromb Diath Haemorrh 1968; 19 (01) 186-197
  • 9 Levin J, Bang FB. The role of endotoxin in the extracellular coagulation of Limulus blood. Bull Johns Hopkins Hosp 1964; 115: 265-274
  • 10 Iwanaga S. The limulus clotting reaction. Curr Opin Immunol 1993; 5 (01) 74-82
  • 11 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145 (3638): 1310-1312
  • 12 MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964; 202 (4931): 498-499
  • 13 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134 (05) 1087-1097
  • 14 Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol 2018; 38 (04) 709-725
  • 15 Mathison JC, Tobias PS, Wolfson E, Ulevitch RJ. Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS. J Immunol 1992; 149 (01) 200-206
  • 16 Tobias PS, Ulevitch RJ. Lipopolysaccharide binding protein and CD14 in LPS dependent macrophage activation. Immunobiology 1993; 187 (3–5): 227-232
  • 17 Dunzendorfer S, Lee HK, Soldau K, Tobias PS. TLR4 is the signaling but not the lipopolysaccharide uptake receptor. J Immunol 2004; 173 (02) 1166-1170
  • 18 da Silva Correia J, Soldau K, Christen U, Tobias PS, Ulevitch RJ. Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD14 to TLR4 and MD-2. J Biol Chem 2001; 276 (24) 21129-21135
  • 19 Ulevitch RJ, Tobias PS. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol 1995; 13 (01) 437-457
  • 20 Poltorak A, He X, Smirnova I. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282 (5396): 2085-2088
  • 21 Park BS, Lee J-O. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med 2013; 45 (12) e66-e66
  • 22 World Health Organization. Sepsis. World Health Organization. Accessed November 21, 2018 at:
  • 23 Gando S, Levi M, Toh C-H. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016; 2 (01) 16037
  • 24 Lerner RG, Goldstein R, Cummings G, Lange K. Stimulation of human leukocyte thromboplastic activity by endotoxin. Proc Soc Exp Biol Med 1971; 138 (01) 145-148
  • 25 Rivers RPA, Hathaway WE, Weston WL. The endotoxin-induced coagulant activity of human monocytes. Br J Haematol 1975; 30 (03) 311-316
  • 26 Semeraro N, Biondi A, Lorenzet R, Locati D, Mantovani A, Donati MB. Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites. Immunology 1983; 50 (04) 529-535
  • 27 Mészáros K, Aberle S, Dedrick R. et al. Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein. Blood 1994; 83 (09) 2516-2525
  • 28 Steinemann S, Ulevitch RJ, Mackman N. Role of the lipopolysaccharide (LPS)-binding protein/CD14 pathway in LPS induction of tissue factor expression in monocytic cells. Arterioscler Thromb 1994; 14 (07) 1202-1209
  • 29 Halvorsen H, Olsen JO, Osterud B. Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets. J Leukoc Biol 1993; 54 (04) 275-282
  • 30 Osterud B. Platelet activating factor enhancement of lipopolysaccharide-induced tissue factor activity in monocytes: requirement of platelets and granulocytes. J Leukoc Biol 1992; 51 (05) 462-465
  • 31 Engstad CS, Lia K, Rekdal O, Olsen JO, Osterud B. A novel biological effect of platelet factor 4 (PF4): enhancement of LPS-induced tissue factor activity in monocytes. J Leukoc Biol 1995; 58 (05) 575-581
  • 32 Herbert JM, Corseaux D, Lale A, Bernat A. Hypoxia primes endotoxin-induced tissue factor expression in human monocytes and endothelial cells by a PAF-dependent mechanism. J Cell Physiol 1996; 169 (02) 290-299
  • 33 Landsem A, Fure H, Christiansen D. et al. The key roles of complement and tissue factor in Escherichia coli-induced coagulation in human whole blood. Clin Exp Immunol 2015; 182 (01) 81-89
  • 34 Subramaniam S, Jurk K, Hobohm L. et al. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood 2017; 129 (16) 2291-2302
  • 35 Weinstein JR, Swarts S, Bishop C, Hanisch U-K, Möller T. Lipopolysaccharide is a frequent and significant contaminant in microglia-activating factors. Glia 2008; 56 (01) 16-26
  • 36 Neumann F-J, Ott I, Marx N. et al. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol 1997; 17 (12) 3399-3405
  • 37 Broze Jr GJ, Leykam JE, Schwartz BD, Miletich JP. Purification of human brain tissue factor. J Biol Chem 1985; 260 (20) 10917-10920
  • 38 Carson SD, Ross SE, Bach R, Guha A. An inhibitory monoclonal antibody against human tissue factor. Blood 1987; 70 (02) 490-493
  • 39 Basavaraj MG, Olsen JO, Østerud B, Hansen J-B. Differential ability of tissue factor antibody clones on detection of tissue factor in blood cells and microparticles. Thromb Res 2012; 130 (03) 538-546
  • 40 Hisada Y, Alexander W, Kasthuri R. et al. Measurement of microparticle tissue factor activity in clinical samples: a summary of two tissue factor-dependent FXa generation assays. Thromb Res 2016; 139 (139) 90-97
  • 41 Morrissey JH, Fair DS, Edgington TS. Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res 1988; 52 (03) 247-261
  • 42 Albrecht S, Luther T, Grossmann H, Flössel C, Kotzsch M, Müller M. An ELISA for tissue factor using monoclonal antibodies. Blood Coagul Fibrinolysis 1992; 3 (03) 263-270
  • 43 Kirchhofer D, Moran P, Chiang N. et al. Epitope location on tissue factor determines the anticoagulant potency of monoclonal anti-tissue factor antibodies. Thromb Haemost 2000; 84 (06) 1072-1081
  • 44 Morrissey JH, Fakhrai H, Edgington TS. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell 1987; 50 (01) 129-135
  • 45 Magdolen V, Albrecht S, Kotzsch M. et al. Immunological and functional analyses of the extracellular domain of human tissue factor. Biol Chem 1998; 379 (02) 157-165
  • 46 Morrissey J, Agis H, Albrecht S. et al. CD142 (Tissue Factor) Workshop Panel report. In: Kishimoto et al, eds. Leucocyte Typing VI: White Cell Differentiation Antigens. New Yor, NY: Garland Publishing, Inc.; 1997: 742-746
  • 47 Huang M, Syed R, Stura EA. et al. The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex. J Mol Biol 1998; 275 (05) 873-894
  • 48 Egorina EM, Sovershaev MA, Bjørkøy G. et al. Intracellular and surface distribution of monocyte tissue factor: application to intersubject variability. Arterioscler Thromb Vasc Biol 2005; 25 (07) 1493-1498
  • 49 Spicer EK, Horton R, Bloem L. et al. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proc Natl Acad Sci U S A 1987; 84 (15) 5148-5152
  • 50 Scarpati EM, Wen D, Broze Jr GJ. et al. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry 1987; 26 (17) 5234-5238
  • 51 Mackman N, Morrissey JH, Fowler B, Edgington TS. Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade. Biochemistry 1989; 28 (04) 1755-1762
  • 52 Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989; 9 (06) 2752-2755
  • 53 Ollivier V, Houssaye S, Ternisien C. et al. Endotoxin-induced tissue factor messenger RNA in human monocytes is negatively regulated by a cyclic AMP-dependent mechanism. Blood 1993; 81 (04) 973-979
  • 54 Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A. Identification of a common nucleotide sequence in the 3′-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A 1986; 83 (06) 1670-1674
  • 55 Mackman N, Brand K, Edgington TS. Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites. J Exp Med 1991; 174 (06) 1517-1526
  • 56 Oeth P, Parry GC, Mackman N. Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression. Arterioscler Thromb Vasc Biol 1997; 17 (02) 365-374
  • 57 Oeth PA, Parry GC, Kunsch C, Nantermet P, Rosen CA, Mackman N. Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site. Mol Cell Biol 1994; 14 (06) 3772-3781
  • 58 Hall AJ, Vos HL, Bertina RM. Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation. J Biol Chem 1999; 274 (01) 376-383
  • 59 Guha M, O'Connell MA, Pawlinski R. et al. Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood 2001; 98 (05) 1429-1439
  • 60 Groupp ER, Donovan-Peluso M. Lipopolysaccharide induction of THP-1 cells activates binding of c-Jun, Ets, and Egr-1 to the tissue factor promoter. J Biol Chem 1996; 271 (21) 12423-12430
  • 61 Napoleone E, di Santo A, Peri G. et al. The long pentraxin PTX3 up-regulates tissue factor in activated monocytes: another link between inflammation and clotting activation. J Leukoc Biol 2004; 76 (01) 203-209
  • 62 Ternisien C, Ramani M, Ollivier V. et al. Endotoxin-induced tissue factor in human monocytes is dependent upon protein kinase C activation. Thromb Haemost 1993; 70 (05) 800-806
  • 63 Ternisien C, Ollivier V, Khechai F, Ramani M, Hakim J, de Prost D. Protein tyrosine kinase activation is required for LPS and PMA induction of tissue factor mRNA in human blood monocytes. Thromb Haemost 1995; 73 (03) 413-420
  • 64 Polack B, Pernod G, Barro C, Doussière J. Role of oxygen radicals in tissue factor induction by endotoxin in blood monocytes. Haemostasis 1997; 27 (04) 193-200
  • 65 Luyendyk JP, Piper JD, Tencati M. et al. A novel class of antioxidants inhibit LPS induction of tissue factor by selective inhibition of the activation of ASK1 and MAP kinases. Arterioscler Thromb Vasc Biol 2007; 27 (08) 1857-1863
  • 66 Pendurthi UR, Williams JT, Rao LVM. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : a possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. Arterioscler Thromb Vasc Biol 1999; 19 (02) 419-426
  • 67 Mackman N. Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. J Biol Chem 1994; 269 (42) 26363-26367
  • 68 Hölschermann H, Dürfeld F, Maus U. et al. Cyclosporine a inhibits tissue factor expression in monocytes/macrophages. Blood 1996; 88 (10) 3837-3845
  • 69 Oeth P, Mackman N. Salicylates inhibit lipopolysaccharide-induced transcriptional activation of the tissue factor gene in human monocytic cells. Blood 1995; 86 (11) 4144-4152
  • 70 Osnes LT, Foss KB, Joø GB. et al. Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation, and synthesis of tissue factor (TF) and tumor necrosis factor alfa (TNF-alpha) in human monocytes. Thromb Haemost 1996; 76 (06) 970-976
  • 71 De Prost D, Ollivier V, Hakim J. Pentoxifylline inhibition of procoagulant activity generated by activated mononuclear phagocytes. Mol Pharmacol 1990; 38 (04) 562-566
  • 72 Brozna JP, Horan M, Carson SD. Dipyridamole inhibits O2- release and expression of tissue factor activity by peripheral blood monocytes stimulated with lipopolysaccharide. Thromb Res 1990; 60 (02) 141-156
  • 73 Crutchley DJ, Hirsh MJ. The stable prostacyclin analog, iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro. Blood 1991; 78 (02) 382-386
  • 74 Ollivier V, Ternisien C, Vu T, Hakim J, de Prost D. Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin-activated human monocytes. FEBS Lett 1993; 322 (03) 231-234
  • 75 Ollivier V, Parry GCN, Cobb RR, de Prost D, Mackman N. Elevated cyclic AMP inhibits NF-kappaB-mediated transcription in human monocytic cells and endothelial cells. J Biol Chem 1996; 271 (34) 20828-20835
  • 76 Ferro D, Basili S, Alessandri C, Cara D, Violi F. Inhibition of tissue-factor-mediated thrombin generation by simvastatin. Atherosclerosis 2000; 149 (01) 111-116
  • 77 Markle RA, Han J, Summers BD. et al. Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells. J Cell Biochem 2003; 90 (01) 23-32
  • 78 Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol 1997; 17 (02) 265-272
  • 79 Nagata K, Ishibashi T, Sakamoto T. et al. Rho/Rho-kinase is involved in the synthesis of tissue factor in human monocytes. Atherosclerosis 2002; 163 (01) 39-47
  • 80 Guha M, Mackman N. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 2002; 277 (35) 32124-32132
  • 81 Herbert JM, Savi P, Laplace MC, Lale A. IL-4 inhibits LPS-, IL-1 β- and TNF α-induced expression of tissue factor in endothelial cells and monocytes. FEBS Lett 1992; 310 (01) 31-33
  • 82 Herbert JM, Savi P, Laplace M-C. et al. IL-4 and IL-13 exhibit comparable abilities to reduce pyrogen-induced expression of procoagulant activity in endothelial cells and monocytes. FEBS Lett 1993; 328 (03) 268-270
  • 83 Pradier O, Gérard C, Delvaux A. et al. Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 1993; 23 (10) 2700-2703
  • 84 Ramani M, Ollivier V, Ternisien C. et al. Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation. Br J Haematol 1993; 85 (03) 462-468
  • 85 Ernofsson M, Tenno T, Siegbahn A. Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines. Br J Haematol 1996; 95 (02) 249-257
  • 86 Ansari SA, Pendurthi UR, Rao LVM. Role of cell surface lipids and thiol-disulphide exchange pathways in regulating the encryption and decryption of tissue factor. Thromb Haemost 2019; 119 (06) 860-870
  • 87 Kapopara PR, Safikhan NS, Huang JL. et al. CD248 enhances tissue factor procoagulant function, promoting arterial and venous thrombosis in mouse models. J Thromb Haemost 2021; 19 (08) 1932-1947
  • 88 Beckmann L, Rolling CC, Voigtländer M. et al. Bacitracin and rutin regulate tissue factor production in inflammatory monocytes and acute myeloid leukemia blasts. Cancers (Basel) 2021; 13 (16) 3941
  • 89 Beckmann L, Mäder J, Voigtlaender M. et al. Inhibition of protein disulfide isomerase with PACMA-31 regulates monocyte tissue factor through transcriptional and posttranscriptional mechanisms. Thromb Res 2022; 220: 48-59
  • 90 Wang J, Pendurthi UR, Rao LVM. Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity. Blood 2019; 134 (07) 645-655
  • 91 Taylor Jr FB, Chang A, Ruf W. et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33 (03) 127-134
  • 92 Levi M, ten Cate H, Bauer KA. et al. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93 (01) 114-120
  • 93 Carmeliet P, Mackman N, Moons L. et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383 (6595): 73-75
  • 94 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 1996; 93 (13) 6258-6263
  • 95 Toomey JR, Kratzer KE, Lasky NM, Stanton JJ, Broze Jr GJ. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88 (05) 1583-1587
  • 96 Parry GC, Erlich JH, Carmeliet P, Luther T, Mackman N. Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 1998; 101 (03) 560-569
  • 97 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 (04) 1342-1347
  • 98 Yang X, Cheng X, Tang Y. et al. Bacterial endotoxin activates the coagulation cascade through gasdermin D-dependent phosphatidylserine exposure. Immunity 2019; 51 (06) 983.e6-996.e6
  • 99 Osterud B, Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis. Thromb Haemost 1983; 49 (01) 5-7
  • 100 Franco RF, de Jonge E, Dekkers PE. et al. The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation. Blood 2000; 96 (02) 554-559
  • 101 Pawlinski R, Tencati M, Holscher T. et al. Role of cardiac myocyte tissue factor in heart hemostasis. J Thromb Haemost 2007; 5 (08) 1693-1700
  • 102 Pawlinski R, Wang JG, Owens III AP. et al. Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice. Blood 2010; 116 (05) 806-814
  • 103 Davidson SM, Boulanger CM, Aikawa E. et al. Methods for the identification and characterization of extracellular vesicles in cardiovascular studies - from exosomes to microvesicles. Cardiovasc Res 2023; 119 (01) 45-63
  • 104 Satta N, Toti F, Feugeas O. et al. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol 1994; 153 (07) 3245-3255
  • 105 Aras O, Shet A, Bach RR. et al. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 2004; 103 (12) 4545-4553
  • 106 Lee RD, Barcel DA, Williams JC. et al. Pre-analytical and analytical variables affecting the measurement of plasma-derived microparticle tissue factor activity. Thromb Res 2012; 129 (01) 80-85
  • 107 Vallier L, Bouriche T, Bonifay A. et al. Increasing the sensitivity of the human microvesicle tissue factor activity assay. Thromb Res 2019; 182 (182) 64-74
  • 108 Franco C, Lacroix R, Vallier L. et al. A new hybrid immunocapture bioassay with improved reproducibility to measure tissue factor-dependent procoagulant activity of microvesicles from body fluids. Thromb Res 2020; 196 (196) 414-424
  • 109 Woei-A-Jin FJ, De Kruif MD, Garcia Rodriguez P, Osanto S, Bertina RM. Microparticles expressing tissue factor are concurrently released with markers of inflammation and coagulation during human endotoxemia. J Thromb Haemost 2012; 10 (06) 1185-1188
  • 110 Mooberry MJ, Bradford R, Hobl EL, Lin FC, Jilma B, Key NS. Procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia. J Thromb Haemost 2016; 14 (05) 1031-1042
  • 111 Wang J-G, 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 (07) 1092-1098
  • 112 Campbell RA, Hisada Y, Denorme F. et al. Comparison of the coagulopathies associated with COVID-19 and sepsis. Res Pract Thromb Haemost 2021; 5 (04) e12525
  • 113 Hellum M, Øvstebø R, Brusletto BS, Berg JP, Brandtzaeg P, Henriksson CE. Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock. Thromb Res 2014; 133 (03) 507-514
  • 114 Meng S, Kang K, Fei D. et al. Preliminary study of microparticle coagulation properties in septic patients with disseminated intravascular coagulation. J Int Med Res 2021; 49 (05) 3000605211014094
  • 115 von Brühl M-L, Stark K, Steinhart A. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (04) 819-835
  • 116 Osterud B, Due Jr J. Blood coagulation in patients with benign and malignant tumours before and after surgery. Special reference to thromboplastin generation in monocytes. Scand J Haematol 1984; 32 (03) 258-264
  • 117 Johnson GJ, Leis LA, Bach RR. Tissue factor activity of blood mononuclear cells is increased after total knee arthroplasty. Thromb Haemost 2009; 102 (04) 728-734
  • 118 White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158 (14) 1525-1531
  • 119 Schroder K, Tschopp J. The inflammasomes. Cell 2010; 140 (06) 821-832
  • 120 Swanson KV, Deng M, Ting JP-Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 2019; 19 (08) 477-489
  • 121 Wu R, Wang N, Comish PB, Tang D, Kang R. Inflammasome-dependent coagulation activation in sepsis. Front Immunol 2021; 12: 641750
  • 122 Tang D, Wang H, Billiar TR, Kroemer G, Kang R. Emerging mechanisms of immunocoagulation in sepsis and septic shock. Trends Immunol 2021; 42 (06) 508-522
  • 123 Ryan TAJ, Preston RJS, O'Neill LAJ. Immunothrombosis and the molecular control of tissue factor by pyroptosis: prospects for new anticoagulants. Biochem J 2022; 479 (06) 731-750
  • 124 Yang D, He Y, Muñoz-Planillo R, Liu Q, Núñez G. Caspase-11 requires the pannexin-1 channel and the purinergic P2X7 pore to mediate pyroptosis and endotoxic shock. Immunity 2015; 43 (05) 923-932
  • 125 Peng Y, Gao M, Liu Y. et al. Bacterial outer membrane vesicles induce disseminated intravascular coagulation through the caspase-11-gasdermin D pathway. Thromb Res 2020; 196: 159-166
  • 126 Shi J, Tang Y, Liang F. et al. NLRP3 inflammasome contributes to endotoxin-induced coagulation. Thromb Res 2022; 214 (214) 8-15
  • 127 Wu C, Lu W, Zhang Y. et al. Inflammasome activation triggers blood clotting and host death through pyroptosis. Immunity 2019; 50 (06) 1401.e4-1411.e4
  • 128 Rao LVM, Pendurthi UR. Regulation of tissue factor coagulant activity on cell surfaces. J Thromb Haemost 2012; 10 (11) 2242-2253
  • 129 Zhang H, Zeng L, Xie M. et al. TMEM173 drives lethal coagulation in sepsis. Cell Host Microbe 2020; 27 (04) 556-570.e6
  • 130 Fu P, Birukova AA, Xing J. et al. Amifostine reduces lung vascular permeability via suppression of inflammatory signalling. Eur Respir J 2009; 33 (03) 612-624
  • 131 Kataoka H, Ushiyama A, Akimoto Y, Matsubara S, Kawakami H, Iijima T. Structural behavior of the endothelial glycocalyx is associated with pathophysiologic status in septic mice: an integrated approach to analyzing the behavior and function of the glycocalyx using both electron and fluorescence intravital microscopy. Anesth Analg 2017; 125 (03) 874-883
  • 132 Mackman N, Sachetto ATA, Hisada Y. Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods. Curr Opin Hematol 2022; 29 (05) 266-274
  • 133 Sachetto ATA, Archibald SJ, Bhatia R, Monroe D, Hisada Y, Mackman N. Evaluation of four commercial ELISAs to measure tissue factor in human plasma. Res Pract Thromb Haemost 2023; 7 (03) 100133
  • 134 Rosell A, Moser B, Hisada Y. et al. Evaluation of different commercial antibodies for their ability to detect human and mouse tissue factor by western blotting. Res Pract Thromb Haemost 2020; 4 (06) 1013-1023
  • 135 Zhang Y, Cui J, Zhang G. et al. Inflammasome activation promotes venous thrombosis through pyroptosis. Blood Adv 2021; 5 (12) 2619-2623
  • 136 Campos J, Ponomaryov T, De Prendergast A. et al. Neutrophil extracellular traps and inflammasomes cooperatively promote venous thrombosis in mice. Blood Adv 2021; 5 (09) 2319-2324
  • 137 Antoniak S, Mackman N. Coagulation, protease-activated receptors, and viral myocarditis. J Cardiovasc Transl Res 2014; 7 (02) 203-211
  • 138 Schechter ME, Andrade BB, He T. et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Sci Transl Med 2017; 9 (405) eaam5441
  • 139 Funderburg NT, Mayne E, Sieg SF. et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood 2010; 115 (02) 161-167
  • 140 Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 2003; 188 (11) 1618-1629
  • 141 Hottz ED, Martins-Gonçalves R, Palhinha L. et al. Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19. Blood Adv 2022; 6 (17) 5085-5099
  • 142 Hottz ED, Azevedo-Quintanilha IG, Palhinha L. et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood 2020; 136 (11) 1330-1341
  • 143 Girard TJ, Antunes L, Zhang N. et al. Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease. J Thromb Haemost 2023; 21 (03) 629-638
  • 144 Rosell A, Havervall S, von Meijenfeldt F. et al. Patients with COVID-19 have elevated levels of circulating extracellular vesicle tissue factor activity that is associated with severity and mortality-brief report. Arterioscler Thromb Vasc Biol 2021; 41 (02) 878-882
  • 145 Guervilly C, Bonifay A, Burtey S. et al. Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19. Blood Adv 2021; 5 (03) 628-634
  • 146 Francischetti IMB, Toomer K, Zhang Y. et al. Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection. EClinicalMedicine 2021; 39: 101069
  • 147 Mackman N, Grover SP, Antoniak S. Tissue factor expression, extracellular vesicles, and thrombosis after infection with the respiratory viruses influenza A virus and coronavirus. J Thromb Haemost 2021; 19 (11) 2652-2658
  • 148 Geisbert TW, Hensley LE, Jahrling PB. et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 2003; 362 (9400): 1953-1958
  • 149 Salet DM, Bekkering S, Middeldorp S, Van DenHoogen LL. Targeting thromboinflammation in antiphospholipid syndrome. J Thromb Haemost 2023; 21 (04) 744-757