Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured various coagulable factors and molecular markers in plasma and serum in the disease group including DIC, DIC suspect, thrombosis, acute myocardial infarction, angina pectoris, sepsis, malignant tumor and type II diabetes and the healthy subject group, and surmised the intravascular coagulative-fibrinolytic activity in each disease group compared with the healthy group. Additionally we selected parameters useful for early detection of the pre-thrombotic state and hypercoagulable state. As a result, of the parameters for the coagulative system, those considered useful were the assay of soluble fibrin monomer complexes using the synthetic substrate (FM.Oita), assay of soluble fibrin monomer complexes using HPLC(SFMC.Oita) and thrombin-anti-thrombin III complex (TAT) in this order. Of the parameters for the fibrinolytic system, those considered useful were FDP assay using ELISA (FDP.Oita) and plasmin-alpha 2 plasmin inhibitor complex (PIC). This FDP.Oita had a considerably high detection sensitivity compared with the FDP assay (Diayatron Co.) using the latex photometric immunoassay which has been commercially available. When measurement was made with plasma and serum in the subject disease group as the sample by the high sensitivity assays mentioned above, it was made clear that both the coagulative activity and fibrinolytic activity are increased, albeit with some differences in intensity, in all the disease groups compared with the healthy group. In order for the hypercoagulable state and pre-thrombotic state to be detected, it is important to know the balance between the coagulative activity and fibrinolytic activity. According to the results of the present experiment, a significant directly proportional correlation was recognized between FM.Oita and FDP.Oita and between TAT and FDP.Oita. Therefore, examination of these ratios will be a more detailed indicator of coagulative-fibrinolytic activity than the TAT/PIC ratio, PAI-1/TPA ratio and ATIII/alpha 2 PI ratio hitherto in use. If useful molecular markers such as FM.Oita are measured over time in various cases and these data are compiled and analyzed statistically, it will not be long before the criteria for the hypercoagulable state and pre-thrombotic state are established.
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PMID:[Molecular marker for detecting hypercoagulable state]. 810 79

Three cases of MPM complicated with DIC were reported in a total of 6862 autopsies (0.04%) from 1950 to 1989 year in our university hospital. All the three cases showed hemorrhagic patches, shock, decreased platelets and fibrinogen, and prolonged prothrombin and thrombin time. Hyaline thrombosis was observed in the pulmonary interstitial microvessels. We have also discussed the diagnosis and pathogenesis of DIC.
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PMID:[Pleural malignant mesothelioma complicated with disseminated intravascular coagulation]. 815 Apr 48

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.
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PMID:Influence of C1-inhibitor on inflammation, edema and shock. 817 80

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) are the most important factors involved in the regulation of blood fibrinolysis. t-PA converts zymogen plasminogen to plasmin on the surface of endothelial cells to maintain blood fluidity and on the surface of the thrombus to efficiently lyse the thrombus. In circulating plasma, PAI-1 inactivates t-PA by forming an equimolar complex with t-PA to suppress the hyperfibrinolysis of the blood. Both proteins are synthesized by the vascular endothelial cells and secreted from the cells in resting state and in response to several stimuli such as thrombin, endotoxin, cytokines and growth factors. In various diseases such as DIC, thromboembolism and bacterial infection, the plasma concentrations of those two factors vary as a consequence of several stimuli, representing the altered fibrinolytic balance caused by the disease. Measurements of these factors and evaluation of the fibrinolytic balance will be important for determination of the most appropriate method of treatment. Moreover, the high plasma concentration of PAI-1 will be a prognostic marker of the disease and may be a risk factor of thrombotic events. In clinical treatment, t-PA is now widely used as a valuable fibrinolytic agent especially in myocardial infarction.
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PMID:[Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)]. 817 42

Prothrombin fragment F1.2 (F1.2) is a new molecular marker indicating acceleration of blood coagulation. We evaluated a new assay of F1.2 measurement using a micro-titer plate (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.). The assay obtained satisfactory results in intra-assay reproducibility test, inter-assay reproducibility test, dilution linearity test and in vitro recovery test. Normal values of plasma F1.2 were 0.16 +/- 0.09 nmol/l (mean +/- SD) in 108 healthy individuals. Differences in the levels between the sexes were not significant. In patients with DIC (n = 22), plasma F1.2 levels were significantly higher than in normal healthy individuals and were correlated with the levels of thrombin-antithrombin III complex. These findings suggest that this F1.2 assay using a micro-titer plate is clinically useful for the evaluation of the therapeutic effect and diagnosis of hypercoagulable states like DIC.
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PMID:[Evaluation of an enzyme-linked immunosorbent assay for the determination of prothrombin fragment F1.2 (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.) using micro-titer plate]. 836 Oct 24

Thrombomodulin-protein C system plays a very important role for the blood fluidity converting thrombin from a procoagulant protease to an anticoagulant and degrading activated factors Va and V III a. By their properties, both thrombomodulin and protein C may be expected for therapeutic medicines in DIC and some thromboembolic disorders. We reviewed and evaluated the probability of activated protein C and thrombomodulin for DIC treatment. Both appeared to be a very expectant for DIC medicine based on the preliminary clinical or experimental trials. Activated protein C is now under clinical trial in DIC. Recombinant thrombomodulin is also going to start its clinical trial in very near future.
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PMID:[Therapeutic strategy of newly developing medicines for disseminated intravascular coagulation--activated protein C and thrombomodulin]. 838 87

DIC is an acquired disorder in which intravascular coagulation may lead to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is acute and severe, fibrin formation may lead to microvascular thrombosis, and consumption of coagulation factors and platelets may result in a hemorrhagic diathesis. Secondary to or simultaneously with coagulation, the fibrinolytic system may be activated, accentuating the bleeding tendency. All the systems involved in DIC, such as coagulation, fibrinolysis, kallikrein-kinin, complement, and possibly other systems are regulated. Coagulation is the central event of DIC. The different coagulation factor derivatives may be generated that can be determined and used as markers for the degree of DIC and for effective control of therapy. Some of the procoagulant and anticoagulant factors are converted in the course of coagulation to their active forms and activation peptides. The active factor is subsequently neutralized by forming a complex with an inhibitor. Hemostatic molecular markers, D-dimer of cross-linked fibrin degradation products (D-dimer), thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin inhibitor complex (PIC) have all been used for the diagnosis of DIC.
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PMID:[Progress in diagnosis of disseminated intravascular coagulation (DIC)--diagnostic criteria of DIC]. 843 27

The early stage of the state in which coagulation or fibrinolytic pathway is activated has been difficult to be estimated. Recently, it has become possible to detect an early stage of DIC (pre-DIC) due to the development of highly sensitive methods which quantitate so called "molecular markers". Molecular markers can be classified into three groups: 1) activation fragments of coagulation proteins (e.g. F1+2); 2) protease and its inhibitor complex (e.g. TAT, IXa-AT-III, Xa-AT-III and PIC); 3) degradation products (e.g. FPA, FPB beta, SFMC and D-dimer). Among them, F1+2, TAT, FPA and SFMC reflect in vivo thrombin generation, while PIC, FPB beta and D-dimer reflect in vivo plasmin generation. IXa-AT-III and Xa-AT-III may be useful markers to detect hypercoagulable states in an earlier stage of underlying various disorders. Measurement of circulating levels of the zymogens and protease inhibitors is unable to detect small changes caused by low grade DIC or localized thrombotic events. Monitoring plasma levels of molecular markers, however, gives us more specific and accurate information regarding the onset and time course of hypercoagulable states and enable us to diagnose DIC at an early stage and to evaluate the effect of treatment for patients with DIC, specifically.
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PMID:[Diagnosis of predictive state of disseminated intravascular coagulation]. 843 31

Anticoagulant therapy, correction of the hypercoagulable state underlying DIC (disseminated intravascular coagulation), can help the treatment of DIC. Synthetic protease inhibitors, which can block serine proteases, such as thrombin and plasmin, in the coagulative-fibrinolytic system, could prevent activation of coagulation factors and development of DIC, if administered properly. Clinically applicated protease inhibitors at present, such as gabexate mesilate (FOY), nafamostat mesilate (FUTHAN), urinastatin (MIRACLID), do not have the same spectrum of action, but the common characteristics are as follows. These inhibitors may be superior to heparin and do not require antithrombin III for their activities because of the competitive inhibitors to coagulative enzymes. The half time of these agents in human circulating blood is within several minutes and shorter than that of heparin.
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PMID:[Synthetic protease inhibitors in the treatment of disseminated intravascular coagulation]. 843 32

Reproducible disseminated intravascular coagulation in rabbits was provoked by two intravenous injections 24 hours apart of endotoxin from Salmonella enteritidis. There were mild symptoms of DIC before the second injection which considerably increased thereafter. In detail there was a sharp drop of the platelet count and a considerable diminution of Antithrombin III, of Protein C, Plasminogen and Antiplasmin as well as an appearance of fibrin monomer complexes and an increase of the aPTT. When PEG-hirudin in a single dose of 1 mg/kg BW was given simultaneously with the second injection of endotoxin the following alterations were observed: The drop of the platelet count and of the activities of Antithrombin III, Protein C, Plasminogen and Antiplasmin was significantly less pronounced. The fibrin monomer complexes were lower and the aPTT was less prolonged. The thrombin time, however, as a sign of a direct action of hirudin on thrombin was considerably more prolonged than in the controls. The combined effect of these alterations strongly points in the direction of a favourable influence of PEG-hirudin on the course of DIC. It is of special interest that 6 h after the intravenous injection of PEG-hirudin its full effect on the thrombin time was still detectable. This is apparently due to a longer half-life in circulation of PEG-hirudin than of natural hirudin.
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PMID:The effect of a long-acting recombinant hirudin (PEG-hirudin) on experimental disseminated intravascular coagulation (DIC) in rabbits. 847 80


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