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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of 4-amidinophenylpyruvic acid (APPA)--a synthetic thrombin inhibitor--on the incidence of disseminated intravascular coagulation was tested with the aid of a model of the generalized Sanarelli-Schwarzman phenomenon. After application of APPA the thrombogenesis in different organs subsided quite significantly.
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PMID:[Effect of 4-amidinophenylpyruvic acid on the generalized Sanarelli-Shwartzman phenomenon]. 102 90

Various reactions of disseminated intravascular coagulation (DIC) were experimentally induced by infusion of thrombokinase in rats, by administration of endotoxin in rabbits and pigs and by infusion of adrenaline and thrombin in dogs. Low plasma concentrations of recombinant hirudin (r-hirudin; 20-200 ng/ml) were sufficient for the inhibition of the different triggering mechanisms. The studies on the pharmacological profile of r-hirudin in DIC therapy confirm the efficacy of this specific tight-binding thrombin inhibitor.
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PMID:Hirudin in disseminated intravascular coagulation. 189 89

Increase of TAT is reflected by the generation of thrombin in hypercoagulable state. TAT might increase in DIC characterized by the formation of disseminated micro-thrombosis. DIC was classified into three groups according to the results of screening tests (FDP, platelet count, fibrinogen, prothrombin time). TAT values significantly increased in the stage of pre-DIC compared with the control group consisting of DIC prone underlying disease. Pre-DIC was easily detected by an increase of TAT during the clinical course. Management of high TAT began with the use of an anticoagulant such as heparin under the condition of sufficient ATIII level. The lowering effect of TAT was easily obtained by the anticoagulant. In ATIII-deficient DIC, the high TAT reduced with the substitution of ATIII concentrate, though a transient increase of TAT was found during the administration of ATIII. To reduce the high TAT under the deficient state of ATIII, MD805, a synthetic thrombin inhibitor, was introduced to avoid further consumption of ATIII. The TAT was decreased by the use of MD805 without administration of ATIII. MD805 could be used as an effective anticoagulant in high TAT due to DIC under an ATIII-deficient state. Although the TAT improved with an adequate anticoagulation in DIC, spontaneous bleeding sometimes appeared as a complication associated with the high level of alpha 2 plasmin inhibitor plasmin complex. In this case, the combined use of tranexamic acid relieved the bleeding.
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PMID:[Thrombin.antithrombin III complex]. 192 Aug 62

A 63-year-old woman was diagnosed as having blue rubber bleb nevus syndrome (BRBNS) with disseminated intravascular coagulation (DIC). Hematological data showed typical DIC: PT 13.2 sec, activated PTT 55.3 sec, fibrinogen 20 mg/100 ml, FDP-E 928 ng/ml, D-dimer 3,477 ng/ml, platelet count 25 x 10(3)/microliters. Although hypofibrinogenemia was successfully controlled by the continuous infusion of heparin, 10,000 units/day, thrombocytopenia has continued. Based on shortened platelet life span, high level of platelet associated IgG, and increased number of megakaryocyte in the bone marrow, the thrombocytopenia was thought to be due to antiplatelet antibody. Her platelet count returned to normal after intravenous infusion of high-dose gamma globulin (IVIg, Sandoz) at the dose of 400 mg/kg for 2-5 days, while corticosteroid, Gabexate mesilate, synthetic thrombin inhibitor MD-805, urinastatin and warfarin had no effect. Thus, DIC or thrombocytopenia may become a serious complication in some patients with BRBNS and IVIg may be useful for correcting thrombocytopenia in the patient.
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PMID:Blue rubber bleb nevus syndrome with disseminated intravascular coagulation and thrombocytopenia: successful treatment with high-dose intravenous gammaglobulin. 204 21

In order to elucidate a possible role of hypercoagulability leading to disseminated intravascular coagulation (DIC) in the pathogenesis of multiple organ failure (MOF), unfractionated heparin and the related agents were administered to septic rabbits which manifest DIC and MOF. Administration of heparin resulted in prevention of thrombocytopenia, leukopenia and elevation of plasma bilirubin and creatinine. The morphological hepatic damage was also ameliorated by heparin. Similar favorable effects were obtained by the administration of low molecular weight heparin. Dextran sulfate prevented the hepatic damage to some extent without improvement on other parameters. No significant effect was observed by the administration of a synthetic thrombin inhibitor (MD805). These results indicate that the favorable effect of heparin is due to its anticoagulant property, especially anti-Xa activity. Thereby, it is concluded that the hypercoagulable state leading to DIC is a prerequisite for the occurrence of MOF in sepsis.
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PMID:The effect of heparin on multiple organ failure and disseminated intravascular coagulation in a sepsis model. 208 91

Anticoagulant as well as anti-platelet drugs are important medicines for the prophylaxis in various kinds of thrombotic diseases. However, the conventional anticoagulant drugs, heparin and coumarin congeners, have some disadvantages and limitations in clinical usage. Recently newly anticoagulants, both synthetic and recombinant, have been developing. They include synthetic thrombin inhibitor, recombinant hirudin, protein C and thrombomodulin. Here we reviewed synthetic thrombin inhibitor, Argipidine (MD805) in clinical trial and investigated its effect on thrombin catalyzed protein C activation on endothelial cells. Argipidine inhibited the protein C activating activity of thrombin on endothelium in a dose response manner. Next we examined the effect of Argipidine on thrombin-induced endothelin release from cultured endothelial cells. The augmentation of endothelin release from endothelial cells by thrombin was also inhibited by Argipidin. The effect was considered one of the advantage of this drug in the treatment of thrombosis. Recombinant thrombomodulin had potent antithrombotic effect on thrombin-induced acute thromboembolism in mice, suggesting that this may be expectant anticoagulant for DIC or thromboses in human.
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PMID:[Synthetic anticoagulant]. 217 Jul 4

Disseminated intravascular coagulation (DIC) was produced by an infusion of a prothrombin activator (Echis carinatus venom; 30 minutes; 0.5 NIH thrombin equivalent U/kg) in mongrel dogs (Echis group, n = 7). Fibrinogen declined to below measurable levels (less than 25 mg/dl), and fibrin-fibrinogen degradation products appeared (53 +/- 8 micrograms/ml) at end venom infusion in the Echis group. These alterations were not seen when an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine-L-chloromethyl ketone (PPACK) (57 nmol/kg/min for 120 minutes), was given alone (PPACK group, n = 5) or in association with venom (Echis + PPACK group, n = 5). Factor II activity (1% +/- 1%) in the Echis and Echis + PPACK groups was significantly below the PPACK (55% +/- 9%) and the control (79% +/- 2%) levels at 120 minutes. In contrast, factor VIII coagulant (factor VIII:C) activity in the Echis group (1% +/- 1%) remained significantly below that in the Echis + PPACK (68% +/- 8%), PPACK (78% +/- 10%), and control (91% +/- 9%) groups at this interval. No change in factors X (91% +/- 7% to 81% +/- 7%, P not significant) and VII (64% +/- 10% to 48% +/- 11%, P not significant) activities were observed. Hemolysis was observed only in the Echis group, whereas thrombocytopenia and leukopenia were noted in both the Echis and the Echis + PPACK groups. These data show that large amounts of E. carinatus venom produce rapid DIC in vivo, because of the activation of prothrombin. In contrast, the decline in factor VIII:C activity appeared to be the result of the liberated thrombin. PPACK antagonized all of the venom-released thrombin without any major deleterious clotting abnormalities. This inhibitor appears to prevent thrombin-mediated DIC in vivo. In contrast, heparin was found to be an unreliable antagonist of the venom-released thrombin in vitro. PPACK also inhibited the marked hemolysis usually observed after venom. In addition, we found that the esterolytic (N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide HCL) activity of E. carinatus venom degrades fibrinogen in vitro.
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PMID:Disseminated intravascular coagulation following Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor. 308 70

A simple method for biological assay of dermatan sulfate (DS) in plasma is described. DS accelerates thrombin inhibition by heparin cofactor II (HC II). The principle of the assay is to measure the residual amidolytic thrombin activity after a short period of incubation with HC II in defibrinated plasma at low ionic strength. For this method we take advantage of two observations. Firstly, at fixed concentrations of DS and of HC II, the rate of thrombin inhibition increases when the ionic strength of the medium decreases. Secondly, defibrination by bentonite absorption also removes antithrombin III, HC II and for a large part alpha-2 macroglobulin from the plasma, so that no other thrombin inhibitor competes with HC II added as a reagent in a second step. In the conditions described, there is a linear relationship between DS concentrations in plasma from 0 to 2 micrograms/ml and the log of residual thrombin activity. The limit of sensitivity is 0.1 micrograms/ml. The assay displays an acceptable reproducibility in intra-assay, inter-assay and inter-individual experiments. It can be used to measure DS in human, rabbit and rat plasmas. The assay is also sensitive to other HC II activators such as heparin and pentosan polysulfate. DS is effective in experimental thrombosis without any detectable anticoagulant effect ex vivo. Pharmacological concentrations of DS in plasma fall into the range of sensitivity of this assay, which would be helpful in experimental or clinical studies of DS and related glycosaminoglycans.
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PMID:A simple method to measure dermatan sulfate at sub-microgram concentrations in plasma. 321 19

The effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III, fibrinogen and platelets was studied in a rat model of disseminated intravascular coagulation (DIC) induced by thrombin infusion. Antithrombin III is consumed during thrombin infusion to a limited degree. Simultaneous administration of exogenous thrombin inhibitors ameliorates the consumption of fibrinogen and platelets. At high thrombin doses, tolerated only during additional administration of thrombin inhibitors, heparin leads to increased consumption of antithrombin III, whereas hirudin and the synthetic inhibitor do not. In every case, the thrombin effect on fibrinogen and platelets is inhibited.
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PMID:Effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III in thrombin-induced disseminated intravascular coagulation in rats. 342 17

We examined the effect of a synthetic thrombin inhibitor, MCI-9038, on two experimental animal models of disseminated intravascular coagulation (DIC). In a model that DIC induced by the intravenous infusion of thrombin, MCI-9038 suppressed the decrease of platelet count by about 50% at a dose of 0.2 micrograms/kg/min and almost completely at 2 micrograms/kg/min. When MCI-9038 was administered orally, the suppressive effect was also observed. Heparin suppressed the platelet count decrease by about 50% at 1 unit/kg/min. In another model of DIC induced by lactic acid and tissue thromboplastin infusion, MCI-9038 prevented the decrease of platelet count and the consumption of coagulation factors. The suppression effect by about 50% on these changes was observed at a dose of 3.16 micrograms/kg/min. Thromboelastogram pattern indicating the consumption coagulopathy in control experiments was normalized by the MCI-9038 administration. Heparin suppressed the decrease of fibrinogen content as effectively as MCI-9038, but it was less effective on the platelet count decrease. From these results, it was concluded that MCI-9038 might be useful for the treatment of DIC.
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PMID:Effect of a synthetic thrombin inhibitor MCI-9038 on experimental models of disseminated intravascular coagulation in rabbits. 360 10


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