Prevention of Endotoxin-Induced Mortality by Antitissue Factor Immunization

Dackiw, Alan P.B.; McGilvray, Ian; Woodside, Michael; Nathens, Avery B.; Marshall, John C.; Rotstein, Ori D.

doi:10.1001/archsurg.1996.01430240027003

Cited by 45 publications

(23 citation statements)

References 21 publications

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“…A critical early event is widespread intravascular activation of coagulation by tissue factor (TF). Accordingly, inhibition of the initiation phase of clotting [3][4][5][6][7][8][9] or preventing thrombin generation 10 using suitable agents has a significant impact on disease morbidity and mortality in experimental models.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium

Chen

Γιαννόπουλος

Shiels

et al. 2004

Blood

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Section: Introductionmentioning

confidence: 99%

Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium

Chen

Γιαννόπουλος

Shiels

et al. 2004

Blood

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“…8 Administration of anti-TF antibodies reduced mortality in baboon and mouse models of septic shock. 9,10 In addition, administration of other coagulation inhibitors, such as antithrombin III, protein C, and tissue factor pathway inhibitor in various animal models of sepsis, reduced mortality. [11][12][13] Plasminogen activator inhibitor type 1 (PAI-1) inhibits both types of plasminogen activators and reduces fibrinolysis.…”

Section: Introductionmentioning

confidence: 99%

Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model

Pawliński

Pedersen

Kehrle

et al. 2003

Blood

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In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1 ؉/؉ and Egr-1 ؊/؊ mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1 ؉/؉ mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1 ؊/؊ mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1 ؉/؉ mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1 ؊/؊ mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor ␣ in endotoxemic mice. Moreover, Egr-1 ؉/؉ and Egr-1 ؊/؊ mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs. IntroductionSeptic shock is induced in humans by the presence of pathogenic bacteria or fungi in the blood and is associated with a high mortality. 1 In Gram-negative sepsis, lipopolysaccharide (LPS [endotoxin]) is released from Gram-negative bacteria and activates monocytes, endothelial cells, and epithelial cells. In sepsis, the procoagulant molecule tissue factor (TF) is expressed by circulating monocytes, vascular endothelial cells in the spleen, and epithelial cells in the lungs and kidneys. 2-7 TFdependent activation of coagulation and the resulting intravascular fibrin deposition contributes to multiorgan failure. 8 Administration of anti-TF antibodies reduced mortality in baboon and mouse models of septic shock. 9,10 In addition, administration of other coagulation inhibitors, such as antithrombin III, protein C, and tissue factor pathway inhibitor in various animal models of sepsis, reduced mortality. [11][12][13] Plasminogen activator inhibitor type 1 (PAI-1) inhibits both types of plasminogen activators and reduces fibrinolysis. 14 PAI-1 activity is increased in the plasma of patients with Gram-negative sepsis 15 and is likely to contribute to intravascular fibrin deposition. Indeed, inhibition of PAI-1 prevents renal fibrin deposition in endotoxemic rabbits. 16 In a mouse model of endotoxemia, maximal levels of TF mRNA are observed at 8 hours, and induction is observed in bronchial and tubular epithelial cells in the lungs and kidneys, respectively. 2,[5][6][7] In contrast, LPS treatment of mice induces maximal PAI-1 mRNA expression at 3 hours, and PAI-1 is expressed by endot...

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“…In addition, the end result of these processes, DIC and microvascular coagulation, is occasionally one of the pathophysiological developments of endotoxin-induced sepsis [3,4]. Such serious effects are probably intermediated by a manifestation of the cellular procoagulant tissue factor by endothelial cells and cells of monocytes or macrophatic lineage, resulting in an acceleration of the coagulation cascade and fibrin deposition [5].…”

Section: Discussionmentioning

confidence: 99%

Acute Onset of Coagulopathy in a Patient with Kasabach-Merritt Syndrome following Transurethral Resection of Bladder Tumor

Shoji

Nakada²,

Sugano³

et al. 1998

Urol Int

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We report an unusual case of Kasabach-Merritt syndrome in a 62 year-old woman with bladder tumor who suffered from acute consumption coagulopathy that increased the fibrinolytic activity due to the presence of a huge hemangioma in the upper and lower extremities. Two days after the transurethral resection of the solitary bladder tumor, serious hematuria and life-threatening disseminated intravascular coagulation developed. Following treatments with heparin and subsequent steroid treatment, hemorrhage and abnormal hemostatic values improved. It is suggested that extensive investigation of the coagulation system should be done in patients with giant hemangioma, particularly before a surgical procedure.

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Prevention of Endotoxin-Induced Mortality by Antitissue Factor Immunization

Cited by 45 publications

References 21 publications

Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium

Inhibition of intravascular thrombosis in murine endotoxemia by targeted expression of hirudin and tissue factor pathway inhibitor analogs to activated endothelium

Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model

Acute Onset of Coagulopathy in a Patient with Kasabach-Merritt Syndrome following Transurethral Resection of Bladder Tumor

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