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)

As part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first QA exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre's performance in comparison to that of others was adopted, which preserved the confidentiality of each centre's results. The factor VIII clotting activity assay (VIII:C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest between-duplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWF R:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.
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PMID:The measurement of haemostatic factors in 16 European laboratories: quality assessment for the Multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT). 266 75

Eighty patients undergoing total hip replacement (THR) were randomly allocated to three groups. Group I (n = 29) received general anaesthesia, Group II (n = 29) epidural anaesthesia and Group III (n = 22) the same epidural as Group II and the same general anaesthesia as Group I but with a lower isoflurane concentration. Prothrombin time (PT), activated thromboplastin time (APTT), fibrinogen (FG), plasminogen (PG), antithrombin III (AT III), protein C (Proc C), alpha-2-antiplasmin (alpha 2AP), Factor VIII coagulating activity (F VIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand ristocetin cofactor (vWF:Rcof), tissue plasminogen activator (tPA) as antigen and activity were measured before induction (A), at the end of surgery (B), on the first postoperative morning (C) and 7 days postoperatively (D). The most relevant finding was that AT III was equally depressed immediately after surgery in all groups, but returned to normal significantly faster in the epidural group (mean values at C: 96.2% in Group I, 104.1% in Group II, 92.7% in Group III). The faster return to normal of AT III after epidural anaesthesia could be one of the mechanisms responsible for the beneficial effect of this technique on the prevention of thromboembolic complications.
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PMID:Coagulation and fibrinolytic parameters in patients undergoing total hip replacement: influence of the anaesthesia technique. 268 46

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
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PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

Protein C--vitamin K-dependent protein of the blood coagulation system possessing anticoagulant and fibrinolytic activities was under investigation. Activated partial thromboplastin time was shown to prolong to 214 +/- 8.9% from the first minute after intravenous administration of 0.51 mg per rat bovine protein Ca. After 5 minutes the activity of plasminogen activators increased to 339 +/- 52.8%. Both effects gradually diminished and came back to the starting level within 60-90 minutes. The factor V activity reduced two-fold and didn't return to basal level. We propose that protein Ca reveals its enzymatic activity within first minutes after administration and is blocked then with its inhibitor.
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PMID:[Generation of blood anticoagulant and fibrinolytic activity after intravenous administration of protein C-a in rats]. 291 69

We found a new thrombophilic tendency in a family with protein S deficiency. The propositus, a 38-year-old Japanese man, is an offspring of consanguineous marriage and suffered from recurrent episodes of thromboembolism. Hemostatic studies, including platelet counts, platelet aggregation, assays of coagulation factors, and plasminogen activity were all within normal limits. The levels of antithrombin III, alpha 2-macroglobulin, protein C, and protein C inhibitor were also normal. However, functional protein S activity in plasma was markedly decreased (9%) in the propositus. The family study revealed that the reduced levels of functional protein S, less than 5% to 29% of normal (normal range: mean +/- 2 SD of 15 normal adults were 44 to 180%), were found in 11 members of this family over three generations. Six of 11 members had severe protein S deficiency (less than 5%), whereas five had partial deficiency. Four of eight adults with protein S deficiency had recurrent episodes of thrombosis. Immunologic levels of protein S antigen were variable in this family and did not correlate closely with the functional levels. These results suggest that the recurrent thrombotic disease in this family appears to be associated with an inherited deficiency of functional protein S.
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PMID:Inherited deficiency of protein S in a Japanese family with recurrent venous thrombosis: a study of three generations. 293 9

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration-dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.
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PMID:Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets. 294 43

The frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (less than 45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C deficiencies (9%) emerge as the leading identifiable associated abnormalities.
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PMID:The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. 296 50

The effect of purified human activated protein C (APC) on fibrinolysis was studied using a clot lysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125I-fibrinogen and thrombin. All proteins were of human origin. In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-1) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropyl-fluorophosphate. Addition of the cofactors of APC-protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.
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PMID:Activated protein C increases fibrin clot lysis by neutralization of plasminogen activator inhibitor--no evidence for a cofactor role of protein S. 297 9

Hemostatic analyses were carried out on 43 patients with small and non-small cell lung cancer, malignant lymphomas and plasmacytomas prior to, 4 h and 24 h after application of chemotherapy. The fibrinopeptide A (FPA) level and the FPA in vitro generation rate (delta FPA) increased significantly only in the small cell lung cancer and malignant lymphomas after 4 h. This supports the thesis of the clotting activation after cytostatic-induced exposition of the tumour cell thromboplastins. An increase in the FPA was observed in those tumor patients, where a high therapy-induced cell destruction was expected. An increase in the activity of factor VIII, as was seen in acute phase reactions, also led to hypercoagulability. Fibrinogen and plasminogen decreased significantly after chemotherapy. Evidence of relevant contact activation was not found in the missing deviation of the C1 inhibitor. The increase in protein C may possibly be attributed to the high-dose corticoid therapy.
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PMID:[Effect of therapy with cytostatic drugs on the hemostasis system in patients with small cell and non-small cell bronchial cancers, malignant lymphomas and plasmacytomas]. 302 44

Patients with recurrent thrombosis may have one of the thrombophilias described in recent literature. These clotting disorders may involve abnormalities in platelets, fibrinogen, plasminogen, protein C, protein S, or antithrombin III. There is usually a family history of clotting disorders, since most of these are inherited in an autosomal dominant pattern.
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PMID:Thrombophilia: new ideas about old problems. 305 30


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