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

In a trial involving 61 patients suffering from shock and DIC, the relations between the concentration of heparin, the effect of heparin on coagulation and the activity of AT III were studied. The effect of heparin decreased to one-half when the activity of AT III was 75 per cent of the average normal level. At 50 per cent AT III, the effect of heparin was negligible. When AT III was substituted the disappearance rate of the AT III activity from circulation was considerably increased in the case of acute DIC, while the concentration of AT III when measured immunologically, did not show an increased disappearance. This difference suggests increased consumption of AT III by active serine proteases of coagulation. In patients substituted with AT III, the duration of acute DIC was between 16 h and 19 h, while it was 3.3 days in patients who received heparin. The survival rate of most severe cases of DIC showed a distinct trend towards improvement, but significance was lacking, probably due to the small number of comparable cases. When AT III and heparin were given simultaneously, there was no further shortening of the duration of DIC; however, severe bleeding complications occurred in some cases. The substitution of AT III was calculated on the following basis: In acute DIC an increase in AT III activity of 1 per cent can be expected when 1 unit/kg body weight is given. The same dose of AT III increases the plasma level by 1.8 per cent when the clotting system is unaffected.
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PMID:[Antithrombin III substitution in patients in shock]. 608 57

Pathological and inconspicuous AT III measuring values were compared with the clinical findings (arterial occlusive diseases, postthrombotic syndromes, acute profound thrombosis of the pelvic veins and the leg veins, acute heparin tolerance in several basic diseases). After calculatory elaboration of all rightly positive and falsely positive, rightly negative and falsely negative laboratory results becomes evident that the positive power of prognosis of the AT III determination is unsatisfactory for a certain basic disease and the negative evidence in these questionings rather well satisfy for the functional measuring method. - The sensitivity of the functional AT III test for the recognition of increased heparin tolerances is quite satisfactory, and the test for the answer of this questioning also suitable and more sensitive than the immunological proof method. - The high percentage of rightly positive and rightly negative findings of all tested results of apparently healthy persons and the groups of patients represented makes clear, which role plays the AT III as a physiologic inhibitor against coagulation-active serine proteases particularly in DIC and in profound thrombosis of the pelvic and leg veins. - For the observation of the course in profound thrombosis of the pelvic and led veins, features of postthrombotic condition and the DIC at least the functional determination of AT III is decisively important.
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PMID:[Relevance of antithrombin III in thrombogenesis: the diagnosis and therapy of antithrombin III defects]. 646 16

A computer analysis of the coagulation laboratory records at the first department of Hokkaido University Hospital over a three-year period (1979-1981) was performed on 553 patients with presumptive intravascular coagulation. It is indicated that the most important diagnostic tests for DIC were Fbg, FDP, and AT III. DIC may have developed not only in patients with reduced Fbg but also in patients with normal or elevated Fbg. It is necessary to estimate the actual situations in the patients with DIC by utilizing sequential laboratory tests. In DIC, SDS-PAGE patterns of Fbg indicated the marked reduction of LMW Fbg, and the activated fibrin formation must be caused by the high affinity of thrombin for HMW Fbg. Changes in the immunoprecipitative second peak of AT III may indicate the binding of different serine proteases to AT III in DIC. Rapid and simple diagnostic tests for DIC are clinically required. An analysis of the TEG pattern using normal plasma mixed with the patient's plasma can indicate the presence of procoagulant activity in patient plasma. Such a laboratory test using TEG is the most useful and rapid diagnostic test in DIC. An anticoagulant effect of heparin therapy is determined by APTT and heparin levels. The antithrombotic effect of heparin therapy is determined by FPA as an immediate index and by Fbg, FDP, and AT III as a slow index.
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PMID:Estimation of coagulation-fibrinolytic factors in DIC. 666 45

Antithrombin III-heparin cofactor has now been recognized as a major inhibitor of thrombin and other serine proteases in the blood coagulation system. Since the reaction between antithrombin III and serine proteases is irreversible, one would expect antithrombin III consumption in the face of pathologic intravascular coagulation and attendant generation of thrombin, IXa, Xa, XIa, XIIa, and plasmin. Using a new assay system for antithrombin III that is unaffected by heparin or fibrino (geno) lytic degradation products, antithrombin III was monitored before and during therapy in 38 patients who had acute or chronic disseminated intravascular coagulation. It was found that early and significant decreases in anththrombin III occur in disseminated intravascular coagulation and thus may serve as a useful diagnostic tool. It was further found that monitoring antithrombin III during therapy reflected a cessation of antithrombin III consumption and, thus, served as an indicator of the efficacy of therapy in stopping the clotting process. Since the assay system is unaffected by fibrino(geno)lytic degradation products and heparin, it proved useful in monitoring the efficacy of heparin therapy for disseminated intravascular coagulation. In addition for this group of patients, it appeared that mini-heparin therapy and large doses of heparin were equally efficacious in correcting other laboratory abnormalities of disseminated intravascular coagulation, and in controlling clinical hemorrhage in disseminated intravascular coagulation.
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PMID:Antithrombin III patterns in disseminated intravascular coagulation. 736 82

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

1. Nafamostat mesilate (NM) is a novel serine-protease inhibitor used for the treatment of acute pancreatitis and disseminated intravascular coagulation. Recently, NM has been reported to cause hyperkalemia due to reduced urinary excretion of potassium (K). 2. This review briefly summarizes the roles of the cortical collecting duct (CCD) in the renal K excretion. 3. In vitro microperfusion technique was applied to examine whether NM, and its two metabolites, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol, directly act on the CCD. 4. It was demonstrated that these compounds act mainly on the apical membrane of the collecting duct cell in the CCD and inhibit the amiloride-sensitive sodium (Na) conductance, resulting in an inhibition of K secretion. PGBA had the most potent action. 5. This direct action of these two metabolites, rather than NM, could contribute to the NM-induced hyperkalemia.
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PMID:Mechanisms of hyperkalemia caused by nafamostat mesilate. 874 49

Gabexate mesylate (GM; commercialized under the brand name FOY) is a nonantigenic synthetic inhibitor of plasmatic and pancreatic serine proteinases that is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. The inhibitory effect of GM on nitric oxide synthase as well as serine proteinases and swine kidney copper amine oxidase, all acting on cationic substrates, has been investigated. On the basis of the available X-ray crystal structures of the enzymes considered, the possible binding mode(s) of GM has(have) been analyzed. The enzyme cross-inhibition by GM suggests that the use of this drug should be under careful control. With the aim to improve the scarce plasma stability of GM, the positively charged drug has been complexed to the surface of preformed anionic liposomes. The liposome-complexed GM half-life increases about five-fold, indicating the protective effect of liposomes on GM degradation. Moreover, the GM complexation with liposomes does not alter its inhibitory activity on NOS-I and porcine pancreatic trypsin.
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PMID:Cross-enzyme inhibition by gabexate mesylate: formulation and reactivity study. 981 86

Sepsis and major trauma are the two most common causes of disseminated intravascular coagulation (DIC) and are characterized by a sudden increase in inflammatory mediators. In general, the outcome of the patient is determined by the degree of the inflammatory response. In severe cases of sepsis and trauma, cascade systems, such as the coagulation, fibrinolytic and complement systems, are activated beyond the capacity of the autoregulatory mechanisms. During DIC, plasma levels of antithrombin (AT)--a serine protease inhibitor that acts mainly on the serine proteases of the coagulation system--decrease due to the formation and subsequent elimination of complexes between AT and activated coagulation factors. The consumption of AT may start a vicious circle by facilitating further intravascular fibrin formation, followed by ischaemic tissue injury and accelerated activation of blood coagulation. Infusion of AT has an anti-inflammatory effect through its ability to counteract microvascular thrombosis. Furthermore, AT induces the release of prostacyclin from the vessel wall by binding to glycosaminoglycans on the surface of endothelial cells. Prostacyclin has a marked anti-inflammatory effect as a result of its inhibitory effect on neutrophils, monocytes and platelets.
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PMID:The effect of antithrombin on the systemic inflammatory response in disseminated intravascular coagulation. 1010 94

Solvent/detergent (S/D)-treated plasma is currently marketed by the American Red Cross as a virally inactivated alternative to fresh-frozen plasma (FFP). The serpin-type serine proteinase inhibitors have a flexible reactive site loop (RSL) that can convert from the active conformation to the inactive latent or polymerized conformations when exposed to heat and/or detergents. We have compared the conformational stability and inhibitory activity of 3 plasma serpins-antithrombin, antitrypsin, and antiplasmin-in S/D plasma and FFP. In S/D plasma, virtually 100% of the antiplasmin and approximately 50% of the antitrypsin are in either the latent or polymerized conformation and lack inhibitory activity, while in FFP only the active conformation is present. Interestingly, antithrombin is not affected by S/D treatment and remains fully active. These data demonstrate that S/D plasma is not simply a virally inactivated equivalent of FFP. The lack of antiplasmin activity and decreased antitrypsin activity in S/D plasma suggest that it may not be as effective as FFP for the treatment of bleeding in patients with systemic activation of proteolytic cascades, such as disseminated intravascular coagulation and sepsis, acquired fibrinolytic states, and large-volume transfusion. Although there has been extensive use of S/D plasma in several European countries with no reports of adverse effects, clinical studies directly comparing the efficacy of these 2 plasma products are needed to directly evaluate the relative therapeutic efficacy of FFP and S/D plasma for the treatment of these diseases.
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PMID:Solvent/detergent-treated plasma has decreased antitrypsin activity and absent antiplasmin activity. 1057 9

Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases, the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K(i)) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees ), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae.
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PMID:Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug. 1117 30


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