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)

The extent and time course of changes in selected procoagulant and anticoagulant factors were investigated in 19 patients undergoing elective abdominal aortic surgery. The coagulation factors were measured preoperatively, and on days two, four, and six postoperatively. It was found that there were no significant changes outside the normal range in prothrombin time, partial thromboplastin time, or thrombin clotting time. However, there were large increases in the procoagulants, fibrinogen, factor VIII coagulant, factor VIIIRag/von Willebrand factor, and in alpha 1-antitrypsin. Over the same time there were marked decreases in the naturally occurring anticoagulants, protein C and antithrombin III, and in alpha 2-macroglobulin. These changes implied that the patients were "hypercoagulable" in the postoperative period. The maximum changes in the procoagulants occurred on either postoperative day two or day four. The maximum changes in the natural anticoagulants occurred on postoperative day two. There were no significant changes in factor V, factor X, alpha 2-antiplasmin, or platelet aggregability. The timing of the changes coincided with a period of high risk of perioperative myocardial infarction in this group of patients. Thus, it is possible that postoperative hypercoagulability contributes to the development of coronary artery thrombosis and myocardial infarction following abdominal aortic surgery.
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PMID:Postoperative changes in coagulant and anticoagulant factors following abdominal aortic surgery. 128 42

Coumarin congeners are frequently being prescribed in vascular surgery. The complication most often seen in haemorrhage. A less known complication is necrosis of skin and soft tissues. This rare complication is potentially lethal. The etiology is unclear, a relation with protein C deficiency seems likely. Early treatment with vitamin K and heparin may prevent the skin necrosis. After necrosis has occurred, surgical intervention is usually necessary.
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PMID:Skin necrosis, a rare complication of coumarin therapy. 128 39

Antiphospholipid antibodies (APA) are a family of immunoglobulins that react with anionic phospholipids, or anionic phospholipids-protein complexes. Recent evidence would support the latter definition. Lupus anticoagulants (LA) inhibit in vitro phospholipid dependent coagulation tests [e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), and dilute Russell viper venom time (dRVVT)]. This inhibition appears to be specific for reagent phospholipids. The addition of freeze-thawed platelets or activated platelets will result in correction of the LA-induced abnormality. Anticardiolipin antibodies (ACA) are related to LA but appear to be distinct. ACA are detected by solid phase assays (ELISA, RIA) and require a plasma cofactor: beta 2 Glycoprotein-I (beta 2 GPI). ACA and LA activities can be separated in individual patient plasmas by affinity chromatography. In some instances they are of differing isotypes. Preliminary evaluation of beta 2 GPI in coagulation assays suggests it may function as a cofactor for LA activity. Recent work also suggests human prothrombin may represent a necessary cofactor for in vitro LA activity. Paradoxically, patients with LA/ACA may sustain thromboembolic events involving both venous and arterial sites. The prothrombotic properties of LA/ACA have not been satisfactorily characterized. A number of proposals have been reported, including inhibition of prostacyclin (PGI2) generation by endothelial cells, decreased activity of the protein C system, impaired fibrinolysis, and inhibition of beta 2GPI. Among these various hypotheses, down regulation of the protein C system appears most plausible. Also, LA/ACA may interfere with the phospholipase A2-phospholipid substrate complex involved in the generation of arachidonic acid from membrane phospholipids.
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PMID:Antiphospholipid antibodies: proposed mechanisms of action. 128 81

We describe a rare occurrence of a family affected with venous thrombosis, exhibiting a protein C (PC) deficiency and dysfunctional protein S (PS). The propositus and his father developed recurrent venous-thrombosis. Their PC deficiency was characterized by low levels of both antigen and activity, and their dysfunctional PS was suggested by low PS activities despite the presence of normal free PS antigen. Over three generations, six family members had a PC deficiency, and three had both a PC deficiency and a dysfunctional PS. The mode of inheritance of PC deficiency appears to be autosomal dominant.
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PMID:Inherited heterozygous protein C deficiency and dysfunctional protein S with recurrent venous thrombotic diseases: a study of three generations of a Japanese family. 128 25

Venous occlusion (VO) during which thrombin (Th) is postulated to be generated is routinely used for evaluation of fibrinolytic potential of endothelium (E). This study was performed to find out whether VO can also be used for assessment of anticoagulant function of E. VO was performed in 98 male patients (pts) with ischemic heart disease. Levels of protein C (PrC) which is related to Th binding by thrombomodulin and fibrinopeptide A (FpA)--a marker of presence of free Th--were determined together with some other factors of coagulation and fibrinolysis. Differences between pre- and postVO PrC levels fluctuated from -54.8% to +57.3%. According to reaction of PrC to VO pts were divided into 2 groups: 13 pts with increase or no change and 17 pts with decrease (consumption) of PrC. In pts without PrC consumption there was a significant increase in FpA. In pts with PrC consumption FpA was unchanged. In pts with PrC consumption exceeding its median value for this group (14%) PAI-1 antigen level fell significantly (-8.4 + 4%) during VO. Thus PrC consumption after VO indicates that TH is effectively removed from blood stream by endothelial factors. Absence of consumption of PrC is a sign of ineffective anticoagulant function of E. Increase in PrC level during VO in some pts may be due to its escape from tissue depot.
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PMID:[The anticoagulant properties of the endothelium studied by the standard venous occlusion test]. 129 87

Levels of protein C functional activity were studied in twenty-nine full-term infants with symptomatic congenital heart disease, who presented in the neonatal period. Protein C levels on admission ranged from < 10% to 61% (mean 37.7% S. D. 14.1%). Eight of the twenty-nine babies had protein C levels between 1.5 and > 3.0 S. D. below the normal neonatal mean with no parental evidence of familial deficiency. Of these infants with low protein C two developed thrombotic complications and four had evidence of coagulation factor consumption. Critically ill infants were over-represented in the group with low protein C. Severely ill newborn infants with protein C at or below the lower limit of the normal neonatal range may be at increased risk of either a consumptive coagulopathy or major thrombosis.
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PMID:Protein C activity in severely ill newborns with congenital heart disease. 129 67

To investigate the status of the protein C-protein S anticoagulant pathway in thalassemic patients, we measured protein C and protein S levels of plasma of 30 adults and 18 children with beta-thalassemia/HbE disease, beta-thalassemia major and HbE disease. Mean +/- 1 SD values of protein C, protein S and other coagulant proteins produced by the liver were as follows: protein C 50.4 +/- 17.2%; protein S 58.8 +/- 25.5%; antithrombin III 78.1 +/- 12.8%; PLG 86.4 +/- 18.4%; prothrombin 71.0 +/- 13.1%; factor VII 72.7 +/- 21.5%; and factor X 79.2 +/- 15.6%. Protein C and protein S levels of thalassemic patients were significantly lower than those of other coagulant proteins produced by the liver. Decrease in protein C level was stronger than that of proteins S. gamma-Carboxylated protein C levels of splenectomized patients were significantly lower than those of nonsplenectomized patients. Severe decrease of protein C and protein S may be responsible for occurrence of thrombosis in thalassemic patients.
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PMID:Protein C and protein S deficiency in thalassemic patients. 129 96

The study was aimed at an evaluation of individualized indications for antithrombotic therapy for secondary prevention in a group of 40 young survivors (aged 30-40 years) of myocardial infarction, presenting a stable phase of coronary disease. The control group consisted of 19 healthy men, of approximately similar age distribution. The determinations concerned the following: in vitro ADP and collagen induced platelet aggregation, plasma fibrinogen concentration, factor VII, VIII and antithrombin III activity, protein C concentration, spontaneous fibrinolytic activity and fibrinolytic activity after venostasis, plasminogen and alpha-2 antiplasmin activity. Moreover, to determine correlations with hemostatic parameters lipids, apolipoproteins, glucose, uric acid plasma concentration as well as percentages of lipoproteins and glycolyzed hemoglobin were also studied. In the study group various hemostasis disturbances were found: an increased platelet aggregation induced by low concentrations of ADP, increased plasma fibrinogen concentration and factor VII activity, decreased protein C concentration and impaired plasma fibrinolytic activity after venostasis. Some correlations between hemostatic and lipids parameters were also observed. Results of the study have suggested necessity for the individualized antithrombotic prevention in young survivors of myocardial infarction with antiplatelet and/or anticoagulant drugs.
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PMID:[Evaluation of thrombotic risk in young men after myocardial infarction during a period of clinical stability]. 130 May 61

We have applied single-strand conformation polymorphism (SSCP) to the analysis of exon 7 of the anticoagulant protein C (PC) gene, in 13 PC-deficient Spanish families. Abnormal patterns were visualized in three samples from type I or quantitative PC deficient proposita. A previously undescribed mutation due to a TT insertion after nucleotide 6139, between codons Gly-142 and Arg-143 was found in one family. The mutation (6139,ins TT) should result in a frameshift with a stop at codon 156, which agrees with the presence of a type I or quantitative PC deficiency in the affected members of the family. The second mutation identified was a C to T transition at nucleotide 6274, 9 base pairs into intron G. This mutation (6274,C-->T), found for the first time in a Spanish family, is identical to the previously characterized PC Sant Louis. The third mutation was a G to A transition that replaces arginine 178 with glutamine (178,R-->Q). This is the third case of 178,R-->Q mutation in 17 apparently unrelated Spanish families with type I PC deficiency. Furthermore, SSCP analysis allowed the detection of another previously described mutation in a PC-deficient Spanish family (178,R-->W).
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PMID:Protein C deficiency: identification of a novel two-base pair insertion and two point mutations in exon 7 of the protein C gene in Spanish families. 130 54

Hereditary protein C (PC) deficiency is usually associated with a high risk of thrombosis. We report the results of a study undertaken to screen for molecular defects in families with hereditary quantitative PC deficiency. Using a strategy combining polymerase chain reaction amplification of selected gene fragments, denaturing gradient gel electrophoresis of the amplification products, and direct sequencing of fragments with altered melting behavior, we studied the PC gene exons and exon/intron junctions of subjects with hereditary type I PC deficiency. Computer simulation of DNA melting was used to design several sets of primers, each containing a GC-clamp, permitting the complete analysis of each amplified exon sequence. Using this procedure, we identified two previously undescribed mutations located in exon VII: a C-to-T substitution generating a nonsense codon in place of Arg 157 in the mature PC and a G-to-A substitution converting Arg 178 to GIn. The two mutations were detected in, respectively, 3 and 2 apparently independent families. This strategy is therefore a valuable tool for screening patients, and the results emphasize its advantages over plasma assays in individuals with a family history of thrombosis.
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PMID:Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis. 130 59


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