thromboplastin and Bacterial-Infections

The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

Topics: Alzheimer Disease; Animals; Arthritis, Rheumatoid; Bacterial Infections; Blood Coagulation; Brain Injuries; Colitis; Fibrinogen; Humans; Inflammation; Kidney Diseases; Multiple Sclerosis; Muscular Dystrophy, Duchenne; Neoplasms; Pulmonary Fibrosis; Spinal Cord Injuries; Stroke; Thrombin; Thromboplastin; Vascular Diseases

TFPI-tissue factor pathway inhibitor appears to play a primary role in regulating TF-induced coagulation. During CAPD procoagulant and anticoagulant activities of the mesothelium are balanced under normal conditions. The aim of the work was to assess TF and TFPI concentrations during peritonitis in CAPD patients. The study was performed in 9 CAPD subjects with peritonitis and 14 clinically stable CAPD patients. TF, total, free and truncated TFPI, thrombomodulin concentrations were measured in plasma and dialysate; C-reactive protein and tumor necrosis factor-TNF alpha were assayed in serum. In 8 patients with S. aureus peritonitis TF and TFPI were not found in dialysate, but were detectable in a case with E. coli peritonitis. C-reactive protein and TNF alpha significantly elevated at the beginning of peritonitis, fell sharply after the therapy. Further studies are needed to establish whether the kind of bacterial peritonitis (Gram-positive or negative) may affect TF and TFPI in plasma and dialysate in CAPD patients.

Topics: Adult; Aged; Anticoagulants; Bacterial Infections; C-Reactive Protein; Dialysis Solutions; Humans; Lipoproteins; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Staphylococcal Infections; Thrombomodulin; Thromboplastin; Tumor Necrosis Factor-alpha

Topics: Animals; Bacterial Infections; Disease Models, Animal; Mice; Mice, Inbred C57BL; Rats; Spleen; Thromboplastin

Inflammasome activation and subsequent pyroptosis are critical defense mechanisms against microbes. However, overactivation of inflammasome leads to death of the host. Although recent studies have uncovered the mechanism of pyroptosis following inflammasome activation, how pyroptotic cell death drives pathogenesis, eventually leading to death of the host, is unknown. Here, we identified inflammasome activation as a trigger for blood clotting through pyroptosis. We have shown that canonical inflammasome activation by the conserved type III secretion system (T3SS) rod proteins from Gram-negative bacteria or noncanonical inflammasome activation by lipopolysaccharide (LPS) induced systemic blood clotting and massive thrombosis in tissues. Following inflammasome activation, pyroptotic macrophages released tissue factor (TF), an essential initiator of coagulation cascades. Genetic or pharmacological inhibition of TF abolishes inflammasome-mediated blood clotting and protects against death. Our data reveal that blood clotting is the major cause of host death following inflammasome activation and demonstrate that inflammasome bridges inflammation with thrombosis.

Topics: Animals; Bacterial Infections; Biomarkers; Blood Coagulation; Caspases; Cell-Derived Microparticles; Disease Models, Animal; Humans; Inflammasomes; Lipopolysaccharides; Macrophages; Mice; Monocytes; Pyroptosis; Signal Transduction; Thromboplastin; Thrombosis

Tissue factor (TF) is an important factor in extrinsic coagulation. Tissue factor pathway inhibitor (TFPI) is a negative regulator of coagulation mediated by TF. Studies on TF and TFPI focus mainly on adult objects, seldom have been done on newborns, especially on sick newborns. The aim of this study was to observe the changes of TF and TFPI in plasma of newborns with infection jaundice and to research the effect of jaundice and infection on the balance of TF and TFPI in newborns.. The content of TF and TFPI in plasma of 21 jaundiced newborns with infection and 8 jaundiced newborns without infection as control was determined quantitatively with the enzyme-linked immunosorbent assay (ELISA).. The content of TFPI and TF in plasma of jaundiced newborn with infection was significantly higher than that of controls [TFPI (21.0 +/- 4.3) vs. (16.2 +/- 1.9) microg/L, P < 0.01; TF (177 +/- 79) vs. (51 +/- 24) ng/L, P < 0.01]. The ratio of TFPI/TF was significantly lower in newborn with infection jaundice than the controls (137 +/- 61 vs. 319 +/- 67, P < 0.01). The 21 jaundiced newborns with infection were divided into the severe hyperbilirubinemia group (serum bilirubin > or = 205.2 micromol/L, n = 10) and the mild hyperbilirubinemia group (serum bilirubin < 205.2 micromol/L, n = 11). There was no significant difference of TFPI level between the severe hyperbilirubinemia group and mild hyperbilirubinemia group (P > 0.05). The TF content in the severe hyperbilirubinemia group was higher than that in the mild hyperbilirubinemia group (216 +/- 79 vs.141 +/- 63, P < 0.01), while the ration of TFPI/TF was lower in the severe hyperbilirubinemia group than in the mild hyperbilirubinemia group (100 +/- 30 vs. 171 +/- 74, P < 0.01).. Infection might induce imbalance between the coagulation inhibition and activation in newborns. Hyperbilirubinemia can aggravate the imbalance induced by the infection through increasing plasma TF level.

Topics: Bacterial Infections; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Jaundice, Neonatal; Lipoproteins; Male; Thromboplastin

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.

Topics: Apoproteins; Bacteremia; Bacterial Infections; Endotoxins; Erythroblastosis, Fetal; Humans; Infant; Infant, Newborn; Monocytes; Thromboplastin; Toxemia

Endotoxin levels and mononuclear phagocyte thromboplastin activities in samples from peripheral blood and peritoneal fluid were determined in nine patients with secondary bacterial peritonitis (appendicitis with perforation, or diverticulitis) and in five control patients (uncomplicated duodenal ulcer or gallbladder stones). None or only negligible amounts of endotoxin, always less than 0.01 ng/dl (contamination), and no growth of bacteria were detected in controls. In the patients with peritonitis, peritoneal fluid samples always contained gram-negative bacteria, and large amounts (mean, 31.6 ng/dl) of endotoxin were seen. Plasma from these patients also contained endotoxin (mean, 0.56 ng/dl) despite negative blood cultures. Mononuclear phagocytes from controls had low thromboplastin values, whereas both circulating monocytes and peritoneal macrophages from peritonitis patients showed a substantial increase (multifold) of thromboplastin.

Topics: Adolescent; Adult; Aged; Ascitic Fluid; Bacterial Infections; Endotoxins; Female; Humans; Macrophages; Male; Middle Aged; Monocytes; Peritonitis; Phagocytes; Thromboplastin