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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of surface tissue factor procoagulant activity and its shedding by blood monocytes can be induced by several stimuli. Few of these defined situations, other than the presence of bacteria and their toxins, are commonly present in the young human infant. In this study, measurements were made of the percentage of monocytes expressing surface tissue factor apoprotein (TFA) in blood taken from babies in the early weeks of life. Mononuclear cells were separated from blood in an environment free of detectable endotoxin. After exposure to a polyclonal rabbit antibody raised to purified brain TFA and subsequent exposure to a fluorescin-labeled murine anti-rabbit IgG, the cell fluorescent activity was analyzed by flow cytometry. The percentage of monocytes showing strong fluorescence was determined. In every instance when systemic bacterial infection was present, more than 60% of the monocytes examined showed fluorescence indicative of the presence of surface TFA. In a single case of fungal Candida septicemia, none of the monocytes was positive. More than 60% of cells were found to be positive in certain instances where infection was highly probable but not proven. Positive cells were found in three cases of isoimmune hemolytic disease of the newborn, as had been anticipated from previous studies, whereas less than 25% of monocytes derived from babies in the absence of discernible infection or isoimmune hemolytic disease expressed surface TFA (p less than 0.001). These findings provide insight into a possible mechanism of coagulation activation in sepsis and may prove to be a useful predictor of the presence of infection or endotoxemia in young infants.
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PMID:The expression of surface tissue factor apoprotein by blood monocytes in the course of infections in early infancy. 163 18

The plasma level of interleukin-1 beta (IL-1 beta) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma IL-1 beta level. The plasma IL-1 beta level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 +/- 0.19 ng/ml) than in the pre-DIC group (0.05 +/- 0.08 ng/ml) or the non-DIC group (0.09 +/- 0.01 ng/ml). The plasma IL-1 beta level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 +/- 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1 beta, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-1 beta reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.
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PMID:Plasma level of IL-1 beta in disseminated intravascular coagulation. 205 18

Tissue factor is the initiator of the extrinsic coagulation pathway and is an important regulator of haemostasis. Tissue factor is constitutively expressed in numerous cells and tissues, and can be induced in monocytes and endothelial cells by different inflammatory agents. Lymphocytes and serum factors can modulate the expression of tissue factor in monocytes. The regulation of tissue factor expression in monocytes appears to be different from that in endothelial cells. Phorbol myristate acetate can inhibit as well as induce tissue factor activity in monocytes, whereas phorbol myristate acetate only induces the expression of tissue factor in endothelial cells. Tissue factor expression in monocytes from patients with infections is not always associated with DIC. The extrinsic pathway inhibitor may play a role in the development of DIC in patients with sepsis. Deposition of extravascular fibrin may be an important determinant of tissue injury.
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PMID:Cellular regulation of tissue factor. 213 17

Fibrin formation plays an important role in glomerular injury. We therefore examined the procoagulant signal produced by cultured rat mesangial cells. Actively growing mesangial cells produced procoagulant activity (PCA) that was present in intact cells (surface-associated), was inhibitable by cyclohexamide and which, by clotting assay, had the characteristics of tissue factor. This PCA decreased with incubation of cells in serum-deprived medium. Incubation with bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) induced increased detectable tissue factor by mesangial cells within two hours which was maximal by four hours. We conclude that quiescent mesangial cells produce a small amount of tissue factor-like procoagulant activity, and that this PCA can be stimulated by incubation with TNF alpha, LPS or when cells are actively growing in high serum medium. Therefore mesangial cells have the capability of contributing to fibrin formation during inflammatory glomerular injury or sepsis.
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PMID:Tissue factor production by cultured rat mesangial cells. Stimulation by TNF alpha and lipopolysaccharide. 234 26

Plasma or serum extrinsic pathway inhibitor (EPI) activity was measured in 24 patients with disseminated intravascular coagulation (DIC) and in 23 patients with severe hepatocellular disease. EPI was measured as activity in a test sample that inhibited factor VIIa/tissue factor (TF)-catalyzed activation of 3H-factor IX (activation peptide release) in the presence of factor X. Of the 24 patients with DIC, 13 had sepsis and five had metastatic carcinoma, disorders in which tissue factor is believed to initiate DIC. EPI activity ranged from 68% to 300% (mean 134% +/- 50%). Serial measurements in nine patients failed to show depletion of EPI activity coincident with worsening DIC. DIC induced by tissue factor or other activating materials may progress despite normal EPI levels. In the patients with liver disease, of whom 15 had decompensated chronic hepatocellular disease (two fatal cases) and eight had acute fulminant liver failure (seven fatal cases), plasma or serum EPI activity varied from less than 20% to 194%. Values were distributed in a bimodal fashion. EPI activity could not be correlated with either the etiology of the liver disease or the degree of prolongation of the prothrombin time. Patients with chronic hepatocellular disease who survived had normal or elevated EPI activity. Patients with fatal hepatic dysfunction had low, normal, or high values for EPI activity. This must mean that secretion of EPI from cells other than hepatocytes can maintain normal plasma EPI levels.
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PMID:Human plasma extrinsic pathway inhibitor activity: II. Plasma levels in disseminated intravascular coagulation and hepatocellular disease. 278 83

Endotoxemia is frequently associated clinically with disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in vivo is unclear. Modulation of tissue factor (TF) and thrombomodulin (TM) expression on the endothelial surface may be relevant pathophysiologic mechanisms. Stimulation of human umbilical vein endothelial cells with endotoxin (1 microgram/ml) increased surface TF activity from 1.52 +/- 0.84 to 11.89 +/- 8.12 mU/ml-10(6) cells at 6 h (n = 11) which returned to baseline by 24 h. Repeated stimulation at 24 h resulted in renewed TF expression. Endotoxin (1 microgram/ml) also caused a decrease in TM expression to 55.0 +/- 6.4% of control levels at 24 h (n = 10) that remained depressed at 48 h. Both effects were dose and serum dependent. A temporary rise in TF expression accompanied by a sustained fall in TM expression comprise a shift in the hemostatic properties of the endothelium that would favor intravascular coagulation and may contribute to the pathogenesis of DIC in gram-negative septicemia.
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PMID:Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. 302 56

Platelet consumption is a prominent feature of disseminated intravascular coagulation. We investigated whether monocyte procoagulant activity (PCA) might play a role in platelet consumption associated with gram-negative septicemia. Human mononuclear cells exposed in vitro to lipopolysaccharide demonstrated parallel dose-dependent increases in PCA and ability to induce platelet aggregation. Induction of platelet aggregation required the generation of thrombin dependent on coagulation Factors VII, X, and II, and calcium. This is consistent with monocyte tissue factor initiating thrombin generation. A specific monoclonal antimonocyte antibody was used to identify monocytes via indirect immunofluorescence, and demonstrated that all monocytes were included in platelet aggregates. Mononuclear cells that did not express PCA did not induce platelet aggregation and monocytes were not surrounded by platelet clumps. These data suggest that monocytes induced to express tissue factor on their surface may be important mediators of endotoxin-induced platelet, as well as fibrinogen, consumption.
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PMID:Human platelet aggregation is initiated by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide in vitro. 353 97

Septicemia is frequently accompanied by changes in the plasmatic as well as cellular coagulation systems and by microclot formation. The occurrence of a hemorrhagic diathesis and microthrombosis is best explained by the syndrome disseminated intravascular coagulation (= consumption coagulopathy). Disseminated intravascular coagulation can be initiated by different agents and by different pathways. The activation of coagulation by endotoxin is well studied; it is mediated by synthesis of tissue factor by monocytes and endothelial cells. The formation of microthrombi is caused by the precipitation of circulating soluble fibrin under the influence of localizing factors, and it is observed under conditions of reduced fibrinolysis activation. Furthermore, thrombocytopenia, thrombocytopathy and endothelial cell damage caused by a direct effect of the toxic agent contribute to the bleeding diathesis.
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PMID:[Sepsis and blood coagulation]. 371 2

Cultured human umbilical vein endothelial cells synthesize the procoagulant, tissue factor, after exposure to bacterial endotoxin. Wild-type lipopolysaccharide from Escherichia coli 0127:B8 stimulates a five- to 20-fold increase in cellular tissue factor. Similarly, rough or incomplete lipopolysaccharide subunits from mutant bacterial strains, or lipid A prepared by mild acid hydrolysis of whole endotoxin, are also stimulatory. In addition, a lipid A biosynthetic precursor, consisting of a phosphorylated glucosamine disaccharide substituted with four beta-hydroxymyristoyl residues, is stimulatory at nanomolar concentrations. Endothelial cell tissue factor is not detectable on the surface of undisrupted cells, but can activate clotting on the cell surface after oxidant-mediated cell injury. The procoagulant, tissue factor, is synthesized by endothelial cells after stimulation mediated by a moiety contained within the lipid A region of lipopolysaccharide. Exposure of clotting factors at the endothelial cell surface after cell injury suggests a mechanism for the microvascular thrombosis associated with disseminated intravascular coagulation with sepsis.
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PMID:Structural features of endotoxin required for stimulation of endothelial cell tissue factor production; exposure of preformed tissue factor after oxidant-mediated endothelial cell injury. 389 92

Leukocytes can generate procoagulant (tissue factor) activity when incubated with endotoxin. These studies were undertaken to determine whether platelets could influence the procoagulant activity generated by leukocytes. Intact or disrupted platelets (rabbit or human) enhanced the clot-promoting properties of rabbit leukocytes. The enhancing effect of human platelets on human leukocytes required the presence of human serum (devoid of factor VII and X activities). When platelets were incubated with endotoxin in the absence of leukocytes, no increase in their clot-promoting properties was discernible. However, a mixture of platelets, leukocytes, and endotoxin generated procoagulant activity which appeared rapidly and was fivefold greater than that produced by leukocytes incubated with endotoxin alone. The enhancement produced by platelets was even more pronounced if homogenates were used. The platelet effect was examined in more detail by the substitution of membranes, granules, and the "soluble" fraction for whole platelets in the test system. The stimulating activity was localized to the particulate fractions, i.e., membranes and granules. Prior treatment of platelet membranes with phospholipase C or gangliosides or by extraction of lipid resulted in loss of enhancing activity, whereas no inhibition was observed after exposure to neuraminidase or trypsin. It is proposed that platelets contribute a membrane lipoprotein surface which enhances the procoagulant activity generated by leukocytes in the presence of endotoxin. This mechanism may be involved in some of the clinical and pathologic manifestations of gram-negative sepsis with disseminated intravascular coagulation.
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PMID:The stimulatory effect of platelets and platelet membranes on the procoagulant activity of leukocytes. 461 59


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