Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a quantitative blood endotoxin assay using a chromogenic substrate with a perchloric acid pretreatment (PCA-LCT), endotoxemia in various liver diseases was studied. With PCA-LCT, recovery of added endotoxin in human plasma was nearly 90%, as evidenced by an intra- and inter-assay coefficients of variation of 5.7% and 11%, respectively. Because the recovery of endotoxin was not affected in severely icteric plasmas, PCA-LCT proved to be applicable to patients with liver diseases where various degree of jaundice exist. In none of the plasmas from patients with chronic hepatitis, acute hepatitis without hepatic failure or liver cirrhosis without ascites did the endotoxin level exceed the normal range of less than 5 pg/ml. With the presence of ascites, however, endotoxemia became detectable, but at low levels and not in all cases. At the stage of hepatic failure complicated with renal failure or disseminated intravascular coagulation, endotoxemia was more frequent and endotoxin concentration greater. It is uncertain, at present, whether endotoxemia itself is deteriorating factor in hepatic failure or is merely concomitant phenomenon resulting from Kupffer cell failure.
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PMID:Endotoxemia in liver diseases: detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment. 300 75

Disseminated intravascular coagulation (DIC) is a common occurrence during clinical sepsis and can be induced in the experimental host by LPS. Fibrin deposition in the hepatic microcirculation has been observed within 30 min of i.v. injection of LPS. Because mononuclear phagocytes have been shown to produce a PCA after exposure to LPS, we have examined the ability of a homogeneous population of explanted hepatic macrophages to express PCA. Addition of as little as 10 ng/ml of LPS stimulated a 15- to 20-fold increase in PCA over control culture levels within 7 1/2 hr post-treatment. The PCA was found to be membrane-associated, with approximately 90 to 95% of the total PCA present in the cellular lysates, and more than 85% was inhibited by pretreatment of the cells with the diazonium salt of sulfanilic acid, an inhibitor of ecto-enzymes. In contrast to tissue thromboplastin produced by other M phi populations, the H-M phi PCA was found to be markedly sensitive both to heat inactivation at 56 degrees C and to inhibition by 1 mM DFP. Additionally, assays involving both a 1-stage coagulation test as well as an enzyme assay with a Factor Xa-specific substrate (using normal and deficient human plasmas) demonstrated that the H-M phi PCA appears to activate Factor X directly. Unlike tissue thromboplastin, the H-M phi PCA is non-dependent of Factor VII activation. These studies: 1) demonstrate the LPS induces a unique PCA in the H-M phi, and 2) support a role for the H-M phi in the initiation of DIC in endotoxemic shock.
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PMID:The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. 702 10

We have investigated the ability of rat and rabbit leucocytes to generate coagulant activity (PCA) in response to endotoxin in vitro and in vivo. On prolonged incubation with endotoxin (10 microgram/ml f.c.) isolated rabbit leukocytes developed strong PCA as measured by clotting and amidolytic assay. In contrast, rat leucocyte failed to produce any PCA even in the presence of huge amounts of endotoxin (200 microgram/ml f.c.) When rabbits were given two spaced endotoxin injections (25 microgram/kg b.w., 24 h apart) blood leucocytes harvested 30--60 min after the second injection consistently showed marked PCA. Again, unlike injections (up 2 mg/kg b.w.) were completely devoid of PCA. These findings support the view that leucocytes are involved in endotoxin-induced disseminated intravascular coagulation in rabbits. On the other hand the poor response of rat leucocytes to endotoxin might help explain the resistance of rats to DIC and Sanarelli-Shwartzman reaction.
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PMID:Role of leucocyte procoagulant activity in endotoxin-induced DIC: evidence from comparative studies in rats and rabbits. 734 Apr 57

Induction of tissue factor (TF) expression on monocytes and endothelial cells is central to the development of septic coagulopathy. Serum concentrations of endotoxin in septic patients who develop disseminated intravascular coagulation (DIC) do not, however, reach the levels that would directly stimulate TF expression on either monocytes or endothelium. We show, using an in vitro coculture system, that the interaction of monocytes with endothelium induces the expression of significant levels of TF. Unstimulated cocultures of monocytes (2 x 10(4)/well) and endothelial cells (2 x 10(4)/well) produced 35.3 +/- 8.5 mU of PCA/well, representing a 5-fold increase over the combined PCA of each cell type cultured alone (7.1 +/- 1.5 mU, n = 6, P < 0.001). Significant enhancement was also found in the presence of low concentrations of LPS. Induction of TF protein was confirmed by Western blotting. Fixation of monocytes with paraformaldehyde completely abolished TF induction in cocultures, whereas fixation of endothelium had no effect, suggesting that TF induction occurred in monocytes rather than endothelial cells. Induction of TF in cocultures could be further augmented by preincubating the endothelial cells with IFN-gamma. When endothelium was prestimulated with 500 U/ml IFN-gamma there was 142 +/- 11% increase over unstimulated cocultures (n = 5, P < 0.01). TF induction was inhibited by 32 +/- 6% in the presence of anti-ICAM-1 mAb (n = 5, P < 0.01). Our results suggest that monocyte interactions with vascular endothelium, regulated by inflammatory cytokines, and mediated by adhesive ligand binding, leads to the induction of functional monocyte TF protein, which may be responsible for the initiation of DIC in sepsis.
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PMID:Induction of tissue factor expression in human monocyte/endothelium cocultures. 854 49

Human granulocytic ehrlichiosis (HGE) is a recently recognized rickettsial tick-borne febrile illness that may occasionally be complicated by coagulopathy. The agent of HGE (aHGE) is an obligate intracellular pathogen, which replicates in endosomes within neutrophils and their precursors. We hypothesized that aHGE might cause DIC via induction of monocyte tissue factor procoagulant activity (TF PCA). Peripheral blood mononuclear cells (PBMNC) and HL-60 cells were used to model the effect of aHGE infection on monocytes/macrophages. Mononuclear cells inoculated with aHGE in vitro demonstrated approximately a 12-15-fold increase in TF PCA, with peak activity occurring at 8-12 h. HL-60 cells inoculated with aHGE also manifested a 4-6 fold induction of TF PCA, with maximal activity occurring at about 8 h. By comparison, E. Coli lipopolysaccharide (LPS) also induced an increase in TF PCA of an equivalent magnitude, and with a similar time course. Induction of TF did not require inoculation of HL-60 cells with live organism, since heat-inactivated aHGE still stimulated TF PCA expression in the target cells. Furthermore, filtered supernatants from heat-inactivated organisms induced TF PCA suggesting that the effect is due to a soluble mediator produced by the organism. Although aHGE is a gram negative organism, the soluble mediator did not appear to be classic endotoxin in that the supernatants tested negative for endotoxin by the Limulus Amoebocyte assay, and polymixin had no inhibitory effect on aHGE supernatants. We conclude that aHGE induces cells of the myelo-monocytic lineage to synthesize TF, which may contribute to the clinical coagulopathy that can be observed in this condition. An atypical soluble mediator or cellular component of the organism appears to be critically important in TF induction by aHGE.
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PMID:Induction of tissue factor procoagulant activity in myelomonocytic cells inoculated by the agent of human granulocytic ehrlichiosis. 1066 64

Hypercoagulability is a common paraneoplastic complication in dogs with various malignant tumors. Importantly, tissue factor procoagulant activity (TF-PCA) induced by TF-bearing microparticles (TF-MPs) is associated with hypercoagulability in human patients with cancer. However, TF-PCA in tumor cells and the association between circulating TF-MPs and hypercoagulability in dogs with malignant tumors remain poorly understood. Therefore, the present study was conducted to evaluate the TF-PCA in various types of canine tumor cell lines and plasma in dogs with malignant tumors. Mammary gland tumor, hemangiosarcoma, and malignant melanoma cell lines, but not lymphoma cell lines, expressed TF on their surfaces and showed cellular surface and MP-associated TF-PCA. The plasma TF-PCA was elevated in some dogs that naturally developed such tumors. No significant difference was observed in plasma TF-PCA between the disseminated intravascular coagulation (DIC) group (median: 43.40; range: 3.47-85.19; n=5) and non-DIC group (median: 7.73; range: 1.70-16.13; n=12). However, plasma TF-PCA was remarkably elevated in three of five dogs with DIC. To the best of our knowledge, this is the first study to evaluate plasma TF-PCA in dogs with malignant tumors. Further studies must be conducted to determine the cellular origin of TF-MPs and the efficacy of plasma TF-PCA as a biomarker of DIC in dogs with malignant tumors.
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PMID:Tissue factor procoagulant activity in the tumor cell lines and plasma of dogs with various malignant tumors. 3161 84