Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of antithrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.
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PMID:Extrinsic pathway inhibitor in elective surgery: a comparison with other coagulation inhibitors. 259 60

The activity of the extrinsic pathway inhibitor (EPI), which is the factor-Xa-dependent inhibitor of the factor VIIa-tissue thromboplastin complex, was serially determined in 13 patients with postoperative/posttraumatic septicemia, and compared to the activity of antithrombin (AT), heparin cofactor II and protein C (PC). In the survivors (n = 8), initial low values for all the inhibitors normalized during recovery. In the demises (n = 5), a progressive increase in EPI activity was observed until death, whereas progressive decreases were observed for the other inhibitors. No correlation was found between the inhibitor values and the endotoxin concentration. We conclude that EPI activities are increased in the late course of fatal septicemia. Apparently, a large EPI-AT gap is a severe prognostic indicator in such patients.
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PMID:Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: increased levels in fatal cases. 280 38

Thrombomodulin is an endothelial cell protein which accelerates thrombin-dependent protein C activation by over 1000 fold. In this study, the effect of thrombomodulin on the inactivation of thrombin by its serum inhibitors was evaluated. 125I-thrombin was incubated at 37 degrees C with serum and the resulting complexes separated by SDS-PAGE. Antithrombin III was the major complex formed with some 125I-thrombin bound to heparin cofactor II and higher molecular weight fractions. Inclusion of thrombomodulin at increasing concentrations inhibited 125I-thrombin binding to antithrombin III and the higher molecular weight fractions but had little effect on thrombin-heparin cofactor II complex formation. Similar results were obtained using a purified antithrombin III/heparin cofactor II system. Kinetic studies, using purified antithrombin III, revealed that thrombomodulin acts as a weak competitive inhibitor towards antithrombin III (Ki = 39 nM). We postulate that in the microcirculation, where the ratio of thrombomodulin to antithrombin III is relatively high, thrombin bound to thrombomodulin may be protected from inactivation by antithrombin III and can thus promote efficient activation of protein C.
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PMID:The effects of human thrombomodulin on the inactivation of thrombin by its serum inhibitors. 282 75

Inopportune coagulation of blood in vessels is prevented by defense mechanisms, in which plasma inhibitors play an important role. The inhibitors are glycoproteins and belong to two different groups, according to their mechanism of action. The first group consists of the inhibitors of serine proteases, which form inactive complexes with various coagulation enzymes; it includes antithrombin III, heparin cofactor II, alpha 2-macroglobulin, alpha 1-antitrypsin and C1S-inhibitor. The second group includes protein C and its cofactor, protein S. Protein C, activated by thrombin complexed with a protein cofactor present on the endothelial cell surface (thrombomodulin), is responsible for the proteolytic degradation of two coagulation cofactors (Va and VIII: Ca). The clinical importance of both antithrombin III, protein C and protein S is attested by the strong association between recurrent venous thromboembolic manifestations and inherited deficiencies of one or the other of these proteins.
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PMID:[General mechanisms of coagulation and their physiological inhibition. II. The regulation of coagulation by physiological inhibitors]. 286 16

In this communication some of the important regulatory mechanisms involving endothelial cell surface associated anticoagulant reactions as well as endothelial cell surface expressed receptors which directly contribute to the inhibition of coagulation are reviewed. In particular, the mechanism of action of protease inhibitors such as antithrombin III, heparin cofactor II, or protease nexin I and their possible interaction with glycosaminoglycan components of the endothelial cells is critically summarized. Thrombin binding to endothelial cells, in particular to thrombomodulin, is believed to be a major event in the induction of anticoagulatory mechanisms such as the protein C/protein S system which warrant a balanced hemostatic system. Additional components such as vascular anticoagulant or extrinsic pathway inhibitor may also contribute to the anticoagulant potential of the vessel wall. Furthermore, the modulation of these membrane-associated anticoagulant reactions by other components such as heparin-binding proteins is discussed.
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PMID:Anticoagulant potential of endothelial cell membrane components. 306 43

The prevalence of inherited thrombotic syndromes in the general population (1 in 2,500/5,000) appears to be higher than that of inherited bleeding disorders. The problems of their laboratory diagnosis are reviewed and a screening procedure is proposed. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40-45 years, particularly when thrombotic episodes are recurrent. Screening must start from the exclusion of common acquired causes of thrombophilia. A negative family history does not exclude inherited thrombophilia, because the defects have a low penetrance and fresh mutations may have occurred in the propositi. Laboratory screening is based on a two-step procedure. The first step is aimed at detecting, preferably with specific functional assays, the most frequent and well established causes of inherited thrombophilia, i.e. deficiencies or dysfunctions of antithrombin III, protein C, protein S, plasminogen and fibrinogen. The tests included in the second step of the screening are aimed at detecting the less common or less well established causes of inherited thrombophilia (low heparin cofactor II, defective release of tissue plasminogen activator, and high plasminogen activator inhibitor). The simplest, more reliable and specific assay methods to be used in laboratory practice are recommended.
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PMID:Laboratory screening of inherited thrombotic syndromes. 311 99

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.
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PMID:Development of the human coagulation system in the healthy premature infant. 317 44

Patients with inherited defects or abnormalities that impair the naturally-occurring anticoagulant and fibrinolytic systems are at risk of developing venous and, more rarely, arterial thromboembolism. The prevalence of inherited thrombophilia in the general population is higher than that of inherited bleeding disorders (ca. 1 in 7500 vs 1 in 20,000). Low levels or dysfunctional forms of antithrombin III, protein C and protein S and abnormal fibrinogens are the most frequent and well-established inherited causes for thrombosis. Less frequent and/or less established causes are low heparin cofactor II and plasminogen and high levels of plasminogen activator inhibitor and histidine-rich glycoprotein. The pathophysiology, genetic and clinical aspects and laboratory diagnosis of inherited thrombotic disorders are reviewed and an approach to prophylaxis and therapy is outlined.
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PMID:Inherited factors in thrombosis. 328 51

The coagulation inhibitors heparin cofactor II (HC II), antithrombin (AT) and protein C (PC) were measured in healthy term and preterm infants in order to establish reference standards. The mean value for HC II in term infants was found to be about half of the adult values. Values below 25% in healthy infants may suggest hereditary deficiency states. One girl with congenital HC II deficiency was detected. Mean AT and PC levels were somewhat higher than HC II. Healthy preterm infants have significantly lower HC II and AT values than healthy term infants. Serial AT measurements have been used in monitoring seriously ill infants and used as a prognostic indicator. In a small number of unhealthy neonates HC II was reduced to an even greater extent than AT, and on recovery normalized more rapidly than AT.
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PMID:Heparin cofactor II, antithrombin and protein C in plasma from term and preterm infants. 339 3

Five type I protein C deficient male patients received 5 mg stanozolol b.i.d. during 4 weeks. After four weeks of treatment plasma protein C activity increased from 0.42 to 0.74 U/ml and protein C antigen from 0.49 to 0.75 U/ml. This approximately 1.6 fold increase in plasma protein C was accompanied by an increase in factor II antigen (1.5 fold), factor V activity (1.6 fold), factor X antigen (1.1 fold), antithrombin III antigen (1.3 fold) and heparin cofactor II antigen (1.5 fold), while the concentration of factor VII, factor VIII, and factor IX activity, and of protein S antigen remained unchanged. Prothrombin fragment F1+2, measured in two patients, increased 1.3 fold. In addition to its effect on procoagulant and anticoagulant factors stanozolol had profibrinolytic effects, reflected in an increase in tPA activity and in the concentration of plasminogen. These data indicate that in type I protein C deficient patients stanozolol increases the concentrations of both procoagulant and anticoagulant factors and favours fibrinolysis. The efficacy of stanozolol in preventing thrombotic disease in type I protein C deficient patients, however, remains to be established. During the four weeks of stanozolol treatment no thrombotic manifestations were observed in the protein C deficient patients.
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PMID:Treatment of hereditary protein C deficiency with stanozolol. 359 78


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