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)

Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin clotting activity and accelerates thrombin-catalyzed activation of plasma protein C. Its role is considered to be very important to prevent thrombosis. Recently, TM has been found in circulating blood and the roles and the functions have been investigated. In this study, we evaluated the reliance and the clinical usefulness of a TM-measuring-kit by enzyme immunoassay (MGC-01-001: Mitsubishi Gas chemical company). Intraassay reproducibility test, dilution linearity test and in vitro recovery test was obtained satisfactory results. A correlation between plasma and serum on TM levels of healthy individuals was very good and the difference between them was not significant. Normal value of plasma TM levels was instituted 15.73 +/- 6.98 ng/ml by measuring 52 healthy adults. The difference between male and female was not significant. Plasma TM levels did not change significantly after venous occlusion test and on circadian fluctuation. Plasma TM levels in patients with occlusion test and on circadian fluctuation. Plasma TM levels in patients with disseminated intravascular coagulation (DIC) was 40.15 +/- 22.68 ng/ml (mean +/- SD, n = 14). It is significantly higher than the levels in healthy adults. However, the levels in patients with angina pectoris, acute myocardial infarction and aortic aneurysm were not significantly different from those of healthy adults. These findings suggest that the precision of this TM-measuring-kit is satisfactory and the measurement of plasma TM can be useful to diagnose of DIC.
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PMID:[Evaluation of an enzyme immunoassay for plasma thrombomodulin]. 165 17

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C antigen in APC:inhibitor complexes, indicating that protein C activation and inhibition had occurred. In 24 normal plasmas, no detectable APC:PCI complexes were observed (less than 5%). Patients with higher levels of complexes had more abnormal coagulation test data for DIC. The major band of APC complexes detected by anti-protein C antibodies did not react with antibodies to the heparin-dependent protein C inhibitor (PCI-1) previously described. Rather, APC was complexed with another recently described plasma protein C inhibitor, PCI-2. Immunoblotting studies for protein S, the cofactor for APC, revealed that the majority of the DIC patient plasmas contained a higher than normal proportion of protein S in cleaved form, suggesting that protein S may have been proteolytically inactivated. Protein S total antigen levels were also found to be low in DIC patients, excluding those with malignancy. These studies support the hypothesis that the protein C pathway is activated during DIC.
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PMID:Activation and complexation of protein C and cleavage and decrease of protein S in plasma of patients with intravascular coagulation. 252

The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, without the severe side effects associated with bacterial sepsis. Quantitative determination of canine plasma protein C levels were performed using a multiple step amidolytic assay, that included a specific precipitation of the vitamin K-dependent proteins from citrated plasma, followed by thrombin activation (and neutralization) and subsequent measurement of the activated protein C (APC) by chromogen hydrolysis. This investigation demonstrated, that over a twenty-four hour interval, intradermal administration of endotoxin produces a gradual decrease in the PC activity levels, concomitant with a significant reduction in the Factor V, Factor VIII and fibrinogen levels and platelet count, and a prolongation of the Prothrombin Time and Partial Thromboplastin Time. During the first 6 hours, protein C levels fell below the pre-levels and remained significantly lower in the surviving dogs. Thus, this endotoxin-induced DIC animal model permits evaluation of various hemostatic parameters, yet diminishes the severe clinical findings associated with DIC.
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PMID:Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model. 278 30

Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals.
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PMID:Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. 351 Oct 97

Protein C is a vitamin-K-dependent plasma glycoprotein that when activated inhibits coagulation by selectively inactivating the active forms of factor V and factor VIII. A specific antiserum to protein C has been raised, and plasma protein C levels have been measured by means of an electroimmunoassay in several physiological and pathological conditions. In 60 healthy adults there were no differences in protein C related to age or sex; protein C levels ranged from 72 to 139% of values in a normal plasma pool. Low levels were found in 12 healthy full-term newborn infants; the levels in 20 women in the last trimester of normal pregnancy were no different from those in healthy non-pregnant women. In 58 patients with chronic liver diseases protein C levels were lower than those in healthy subjects, in degrees roughly proportional to the severity of the disease. Protein C levels were very low in 21 patients with the disseminated intravascular coagulation syndrome, particularly in those who had evidence of consumption coagulopathy. Very low levels were also found, however, in 20 patients with adult respiratory distress syndrome without consumption coagulopathy. Acquired defects of protein C developed after surgery in the patients operated on for malignancies, after major abdominal operations for benign conditions, and also after relatively minor procedures such as appendicectomy and hernia repair. These findings indicate that protein C deficiencies occur in several conditions associated with increased tendency to thrombosis.
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PMID:Deficiencies of protein C, an inhibitor of blood coagulation. 612 39

When compared to values recorded in the 32 healthy control subjects, plasma protein C activity was found to be significantly decreased in the 29 patients with acute leukemia and especially in those considered to be in a critical condition. On the other hand, plasma antithrombin III activity did not significantly differ from the values noted in control subjects. The concomitantly occurring high plasma fibrinogen levels and low serum cholinesterase activity were highly suggestive for a switch of hepatic protein synthesis towards the production of acute phase proteins. It is therefore considered that in the absence of a consumption coagulopathy, changes affecting plasma protein C and antithrombin III should be related to a modified pattern of hepatic protein synthesis.
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PMID:Plasma protein C and antithrombin III in patients with acute leukemia. 786 37

When compared to 32 healthy normal weight normolipidemic control subjects, plasma protein C antigen and serum cholinesterase activity were significantly decreased in 17 patients with decompensated cirrhosis of the liver and in 29 critically-ill surgical patients displaying the acute phase reaction, most of them without evidence of consumption coagulopathy. The low levels of these variables are considered to be subsequent to impaired and dysregulated hepatic protein synthesis. On the contrary, plasma protein C and serum cholinesterase were increased in 20 nephrotic patients and in 20 overweight hypertriglyceridemic subjects, a finding highly suggestive of enhanced hepatic synthesis probably related to an accelerated turnover of triglycerides. A discrepancy between low serum cholinesterase activity and normal or even high plasma protein C antigen was noted in 15 patients with cholestasis. This was particularly evident in 7 subjects with extrahepatic cholestasis and an abnormal pattern of hepatic protein synthesis or impaired clearance of plasma protein C would appear to develop in such pathological conditions.
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PMID:Clinical studies on plasma protein C. Correlation with serum cholinesterase. 829 22

Various hemostatic and vascular endothelial cell markers were measured in patients with disseminated intravascular coagulation (DIC), non-DIC, or thrombotic thrombocytopenic purpura (TTP) and in healthy volunteers to examine the relationships between the hemostatic abnormalities or vascular endothelial cell injuries and the patients' outcomes. Although the plasma levels of soluble fibrin monomer, thrombin-antithrombin complex, plasmin-plasmin inhibitor complex, and D-dimer were significantly increased in the DIC patients, there were no significant differences in these markers between the DIC patients who survived and those who died, suggesting that these markers might not be directly related to the patient outcome. The plasma thrombomodulin (TM) levels in the DIC and TTP patients were significantly higher than those in the healthy volunteers, and the plasma TM levels in the patients who died were significantly higher than those in the patients who survived. These findings showed that the TM level reflected the outcome, and that the outcome of the diseases underlying DIC and TTP might depend on vascular endothelial cell injuries. The plasma protein C and antithrombin activities were markedly reduced in the DIC, non-DIC, and TTP patients who died compared to those who survived. These findings suggest that reduced plasma antithrombin and protein C activities are useful markers of systemic vascular endothelial injuries. Although the plasma tissue factor (TF) levels were significantly increased in the DIC patients, there was no significant difference in the plasma TF levels between the DIC patients who died and those who survived. In conclusion, we found that the outcome of the diseases underlying DIC and TTP is related to vascular endothelial cells, and that plasma TM, antithrombin, and protein C are useful markers for systemic vascular endothelial cell injury.
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PMID:Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries. 966 69

In order to determine the effect of bacterial proteinases on activation of the protein C system, a negative regulator of blood coagulation, two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, were examined. Each enzyme activated human protein C in a dose- and incubation time-dependent manner. Interestingly, the form of enzyme being composed of a non-covalent complex containing both catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more efficiently than RgpB which contained the catalytic domain alone. The kcat/Km value of RgpA was 18-fold higher than that of RgpB and comparable to that of the thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA catalyzed protein C activation was augmented 1.4-fold by phospholipids, ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could activate protein C in plasma and this resulted in a decrease of the protein C concentration in plasma, which is often observed in patients with sepsis during the development of disseminated intravascular coagulation (DIC). These data indicate that RgpA is a more potent activator of protein C than RgpB and suggest that only the former enzyme can cause protein C activation in vivo. The present study further suggests that bacterial proteinases may possibly contribute to the consumption of plasma protein C which predisposes to DIC and/or promotes a thrombotic tendency towards DIC in sepsis.
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PMID:Activation of protein C by arginine-specific cysteine proteinases (gingipains-R) from Porphyromonas gingivalis. 1006 39


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