Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma levels of antithrombin III, alpha 2-macroglobulin and inter-alpha-trypsin inhibitor, as well as those of various clotting, complement and other plasma factors, were significantly decreased in 18 patients suffering from hyperdynamic septic shock. A similar statistically significant reduction of the concentrations of several plasma factors (prothrombin and antithrombin III, plasminogen and alpha 2-plasmin inhibitor, complement factor C3 and clotting factor XIII) was observed in experimental endotoxaemia. In this model the reduction in the plasma levels of these factors was considerably diminished by the intravenous injection of a granulocytic elastase--cathepsin G inhibitor of lower molecular weight from soybeans. The results of both studies indicate that consumption of plasma factors in the course of Gram-negative sepsis proceeds not only via the classical routes (by activation of the clotting, fibrinolytic and complement cascades by system-specific proteinases such as thrombokinase or the plasminogen activator) but also to an appreciable degree of unspecific degradation of plasma factors by neutral proteinases such as elastase and cathepsin G. The endotoxin-induced release of both sorts of proteinases, the system-specific ones and the unspecific lysosomal proteinases from leucocytes and other cells, is likely to be mainly responsible for the consumption of antithrombin III and alpha-2-macroglobulin via complex formation (followed by elimination of the complexes) and the increased turnover of the inter-alpha-trypsin inhibitor as observed in the clinical study. The therapeutic use of an exogenous elastase--cathepsin G inhibitor in the experimental model was stimulated by the observation that human mucous secretions contain and acid-stable inhibitor of the neutral granulocytic proteinases, called HUSI-I or antileucoproteinase. This inhibitor protects mucous membranes and soluble proteins against proteolytic attack by leucocytic proteinases released in the course of a local inflammatory response. Preliminary results indicate that HUSI-I, which is produced by the epithelial cells of mucous membranes, does not belong to any known structural type of acid-stable proteinase inhibitor. The search for other candidates suitable for medication in humans led to the discovery of a potent elastase--cathepsin G inhibitor, called eglin, in the leech Hirudo medicinalis. This acid-stable inhibitor with a molecular weight close to 8100 has an unusual structural property in that the structure of the molecule is not stabilized by any disulphide bridge.
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PMID:Proteinase inhibitors in severe inflammatory processes (septic shock and experimental endotoxaemia): biochemical, pathophysiological and therapeutic aspects. 39 95

In 12 vascular and 17 trauma cases the changes in the coagulation system due to intraoperative autotransfusion (IAT) were examined immediately after the IAT as well as 24, 48, 72 h and one week later. The following parameters were monitored: 1. Platelet count. --2. Prothrombin-time, partial-thromboplastin-time, factors II, V, VII, X and thrombin-clotting-time. --3. Fibrinogen, alpha-1-antitrypsin, alpha-2-macroglobulin, antithrombin III and plasminogen in 5 trauma cases. --4. Euglobulin-Lysis-Time. --After the IAT a loss of platelets, factors I, II, V, X, plasminogen and antithrombin III was found. Alpha-1-antitrypsin and alpha-2-macroglobulin remained unchanged or showed a slight increase. 24 h after treatment with Ugurol and heparin, fresh frozen plasma, fibrinogen and Cohn I-fraction in selected cases, an increasing normalisation of most parameters was seen, except for the plasma proteins active in coagulation. They showed a combination of "consumption coagulophathy" and "hyperfibrinolysis" up to the 7th day. Under treatment outlines above even marked laboratory changes remained without any clinical significance. Thus our results confirm that IAT does not cause any additional irreversible damage to the coagulation system. Therefore IAT can be considered as method of choice for the emergency treatment of massive bleeding.
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PMID:[Intraoperative autotransfusion and its influence on the blood-clotting-system (author's transl)]. 59 9

We have found that rat plasma corrected the non-activated PT of human normal or factor-X deficient plasma, and the factor Xa-like activity being constantly detected in every 1 ml of blood collected via the cannulated carotid artery of rats. The present study was undertaken to characterize the factor Xa-like activity in rat plasma by preparing rat factor X and a monoclonal antibody against it. Factor X was purified from a BaCl2 eluate of rat plasma by chromatographies on columns of DEAE-Sepharose CL-6B and Sulfate Cellulofine or on a column of Affi-Gel 10 conjugated with a monoclonal antibody against rat factor X. Factor Xa-like activity in rat plasma was eliminated by the treatment of rat plasma with a monoclonal antibody which recognized the heavy chain portions of rat factors X and Xa. A kinetical study demonstrated that rat factor Xa was strongly inhibited by rat antithrombin III, with a Ki of 2.2 x 10(-11) M, in the presence of heparin. However, in the absence of heparin, the second order rate constant for the inhibition of rat factor Xa by rat antithrombin III was 2.6 x 10(4) M-1.min-1, which was one forty-third that for the inhibition of human factor Xa by human antithrombin III. Furthermore, rat factor Xa was resistant to the inhibition by rat alpha-1-antitrypsin and alpha-2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of rat factors X and Xa: demonstration of factor Xa in rat plasma. 171 49

Ten clinically healthy subjects (5 men and 5 women), 31 +/- 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.
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PMID:Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. 212 46

Over a six-month period, 62 endometriosis patients were given 600 mg per day of the ethisterone derivative danazol. Blood count and coagulation status were checked before and during treatment. There was a significant increase (p less than 0.05) in hemoglobin and hematocrit. There were no changes in RBC, leukocyte count, or thrombocyte count; the mean cellular erythrocyte volume, thrombin time, thromboplastin time, and partial thromboplastin time also remained unchanged, as did factors VII, VIII, X, XII, and alpha-1-antitrypsin. Antithrombin III levels increased, while alpha-2-macroglobulin values decreased. Only the drop in fibrinogen, to pathologic values, and the increase in plasminogen reached significant levels (p less than 0.01). These in part contradictory changes suggest that hypocoagulability occurs under danazol medication; however, its clinical relevance is unclear.
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PMID:[Effects of danazol therapy in endometriosis on the blood picture and blood coagulation]. 318 11

The anticoagulant effect of heparin, as reflected by the slope of the relationship between heparin concentration and the logarithm of the activated partial thromboplastin time (APTT), was determined in citrated plasma of seven women in the third trimester of pregnancy and in 10 nonpregnant women of comparable age. Factors II, V, and VII to XII, albumin, individual globulins, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, prothrombin time, and hematocrit were also determined. Baseline APTT (i.e., APTT without heparin) was 30.2 +/- 3.0 sec (mean +/- SD) in the pregnant women and 29.6 +/- 4.7 sec in the controls (NS). The heparin slope value was 1.68 +/- 0.46 ml/U in the pregnant women and 2.33 +/- 0.49 ml/U in the controls, showing that the anticoagulant effect of heparin is decreased in pregnancy. The prothrombin time was also decreased in pregnancy (19.1 +/- 0.8 vs 23.1 +/- 0.5 sec; P less than 0.01). Pregnancy was associated with a significant increase in the activity of factors VII, VIII, IX, and X and in the concentrations of fibrinogen, alpha-1-globulin, and alpha-1-antitrypsin. The plasma albumin concentration was decreased in the pregnant group. In both the pregnant and nonpregnant women (considered separately), the heparin slope value correlated negatively with factor XI activity (r = -0.85 and -0.71; P less than 0.05). Baseline APTT, which was consistently found to correlate with heparin slope value in previous reports on men and nonpregnant women, also showed such correlation in the nonpregnant group of the present study (r = 0.85; P less than 0.05) but not in the group of pregnant women (r = -0.54; NS). The relative heparin resistance in pregnancy in this investigation is consistent with clinical reports of increased heparin requirements during pregnancy.
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PMID:Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin. 686 35

The anticoagulant effect of heparin as reflected by the slope (S) of the relationship between heparin concentration and natural log of activated partial thromboplastin time (APTT) was determined in citrated plasma of 31 hospitalized, 21- to 80-yr-old patients (including many typical candidates for heparin therapy). Also determined were level of factors II, V, VII to XII, albumin, individual globulins, calcium, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, and alpha-2-macroglobulin and prothrombin time and hematocrit. Baseline APTT was 24.1 to 60.3 sec and S was 1.80 to 4.27 ml/u. S correlated with baseline APTT, hematocrit, total protein, functional antithrombin III, prothrombin time, beta-globulin, and factors II, VII, X, XI, and XII. A multiple linear regression equation with baseline APTT, total protein concentration, and factor XI as independent variables was "best" for predicting the S of these patients (r = 0.807, P less than 0.0001). A multiple linear regression equation with baseline APTT and hematocrit as independent variables, obtained in a previous study on healthy subjects, overpredicted the patients' S values. An equation with baseline APTT and gamma-globulins as independent variables yielded the best correlation predicted and actual S values for the combined group of patients and normal subjects (r = 0.715, P less than 0.0001). Our observations indicate that it may be possible to predict the heparin concentration-anticoagulant effect (APTT) relationship for individual patients before institution of heparin therapy.
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PMID:Relationship between concentration and anticoagulant effect of heparin in plasma of hospitalized patients: magnitude and predictability of interindividual differences. 711 66