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)

One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.
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PMID:The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism. 144 Apr 93

The association between congenital deficiencies and recurrent thrombosis strongly suggests that antithrombin III, protein C and protein S play a major role in inhibiting thrombin formation in vivo. Genetic analysis using DNA fragment amplification by polymerase chain reaction and direct gene sequencing has led to the identification of many novel mutations in qualitative and quantitative deficiencies. Elucidation of the molecular basis of these deficiencies is critical to our understanding of natural antithrombotic mechanisms. It not only provides information on the structural features governing protein function, but also permits a better classification, based on genomic abnormalities of hereditary deficiencies responsible for mild to severe phenotypes and may prove of further value to define the most pertinent plasma assays for routine diagnosis.
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PMID:Molecular abnormalities responsible for thrombosis. Genetic aspects. 144 49

Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC-deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening. 145 Mar 21

Serial studies of the plasma protein C-protein S system were performed during the clinical course of a pregnant woman with meningococcaemia who recovered under therapy. The patient had limited purpura fulminans skin lesions and hereditary C4b-binding protein deficiency was suspected. This diagnosis was confirmed in the patient 1 year after delivery and also by family studies. During the meningococcaemia, an initial mild and transient acquired protein C deficiency was seen but no protein S deficiency was observed despite consumption of the latter protein. As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia.
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PMID:Meningococcaemia in an adult with hereditary C4b-binding protein deficiency: study of the variations of the protein S system. 145 Mar 38

This article has summarized known congenital and acquired alterations of hemostasis leading to thrombosis. Decreases in coagulation inhibitors, including antithrombin III, heparin cofactor II, and protein C and protein S, are of major importance in assessing patients with hypercoagulable states or patients with unexplained thrombosis. Newer assays for components of the fibrinolytic system, plasminogen, t-PA and t-PA inhibitor are also now readily available and are important for defining congenital or acquired fibrinolytic defects leading to hypercoagulability and thrombosis. By judicious use of these assays, combined with clinical evaluation, many patients with thrombosis will have an underlying etiologic blood protein defect defined. Delineating reasons for a thrombotic event is of obvious importance for planning long-term prophylactic therapy and for diagnosing and counseling afflicted family members. In this manner, newly found patients can be treated prophylactically before unalterable morbidity or mortality occurs.
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PMID:Hypercoagulability and thrombosis. 145 21

Free protein S, protein C, and C4b-binding protein (C4b-BP) were measured in randomly selected outpatients: 22 with Crohn's disease (CD) and 16 with ulcerative colitis (UC). Active disease was recorded in 10 patients with CD and 4 with UC. Fourteen patients (63.6%) with CD and 4 (25%) with UC had free protein S values below the normal range, with mean values of 62% and 78% of that found in healthy control subjects (p < 0.01). The C4b-BP level was 127% in patients with CD as compared with 89% in both healthy subjects and UC patients (p < 0.01). The protein C levels were similar in the three groups. The present results add to the factors already known favouring thromboembolic complications in inflammatory bowel disease and which might play a major role both for the pathogenesis and for the increased tendency to venous thromboembolism in these diseases.
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PMID:Free protein S deficiency in patients with chronic inflammatory bowel disease. 145 94

Vitamin K-dependent protein S is an anticoagulant plasma protein serving as cofactor to activated protein C in degradation of coagulation factors Va and VIIIa on membrane surfaces. In addition, it forms a noncovalent complex with complement regulatory protein C4b-binding protein (C4BP), a reaction which inhibits its anticoagulant function. Both forms of protein S have affinity for negatively charged phospholipids, and the purpose of the present study was to elucidate whether they bind to the surface of activated platelets or to platelet-derived microparticles. Binding of protein S to human platelets stimulated with various agonists was examined with FITC-labeled monoclonal antibodies and fluorescence-gated flow cytometry. Protein S was found to bind to membrane microparticles which formed during platelet activation but not to the remnant activated platelets. Binding to microparticles was saturable and maximum binding was seen at approximately 0.4 microM protein S. It was calcium-dependent and reversed after the addition of EDTA. Inhibition experiments with monoclonal antibodies suggested the gamma-carboxyglutamic acid containing module of protein S to be involved in the binding reaction. An intact thrombin-sensitive region of protein S was not required for binding. The protein S-C4BP complex did not bind to microparticles or activated platelets even though it bound to negatively charged phospholipid vesicles. Intact protein S supported binding of both protein C and activated protein C to microparticles. Protein S-dependent binding of protein C/activated protein C was blocked by those monoclonal antibodies against protein S that inhibited its cofactor function. In conclusion, we have found that free protein S binds to platelet-derived microparticles and stimulates binding of protein C/activated protein C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Binding of anticoagulant vitamin K-dependent protein S to platelet-derived microparticles. 146 47

The clinical status of 418 consecutive thrombotic patients was assessed and they were investigated for deficiencies of the proteins involved in the modulation of blood coagulation and fibrinolysis. The whole cohort was divided into two groups according to the age at which the first thrombotic event occurred: group 1 younger than 45 years and group 2 older than 45 years. Deficiencies were significantly more frequent in the juvenile thrombotic population; in this subset of patients the prevalences of single deficiencies were: protein S (6.9%), protein C (4.9%), antithrombin III (3%), plasminogen (0.5%) and dysfibrinogenemia (0.3%). It was possible to diagnose 41 additional deficiencies in the relatives of the probands. The clinical picture and the presence, absence and type of predisposing factors were not statistically different in deficient and non-deficient patients. However, deficient patients experienced their first episode significantly earlier than non-deficient patients and had a significantly higher number of recurrences and pulmonary embolism episodes. From the analysis of the thrombosis-free survival curves, there is no doubt that age represents a strong cofactor in thrombotic risk-related deficiency.
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PMID:Clinical and biological aspects of juvenile thrombophilia. 146 39

Previous studies have demonstrated that platelets or aortic endothelial cells provide an appropriate surface that augments the proteolytic inactivation of factor Va by activated protein C (APC). We have examined the ability of three human tumor cell lines (HepG2, CAPAN-2 and J82) to support the inactivation of human factor Va by human APC in the presence and absence of human protein S. APC-mediated factor Va inactivation on these tumor cell lines was assessed by measuring the ability of residual cell-bound factor Va to augment the proteolytic activation of prothrombin by factor Xa. Each of the tumor cell lines studied supported factor Va inactivation by APC in the presence of calcium ions. HepG2 cell monolayers supported this reaction most effectively, with CAPAN-2 and J82 cell monolayers exhibiting moderate and weak effectiveness, respectively. Although not essential for this reaction, protein S moderately enhanced the rate of factor Va inactivation by APC on these tumor cell lines. In addition, pretreatment of each tumor cell line with rabbit antihuman protein S IgG had little, if any, effect on its ability to support factor Va inactivation by APC. Our data suggest that these, and perhaps other, tumor cells can provide an appropriate phospholipid surface for promoting factor Va binding and rapid inactivation by APC.
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PMID:Inactivation of factor Va by activated protein C on selected human tumor cell lines. 146 18

Of 67 patients with acute deep vein thrombosis of the lower extremity (DVT), 43 patients were treated by venous thrombectomy and 24 patients were managed by conservative treatment. The clinical effect of thrombectomy was evaluated by analyzing follow-up results in the 2 groups. The cumulative incidences of pigmentation and stasis ulcer at the 5th year were 2.7% and 0% respectively in the thrombectomy group, and 24.3% and 10% respectively in the conservative treatment group. Pigmentation and stasis ulcer were significantly more frequent in the conservative treatment group (p < 0.01). It is concluded that venous thrombectomy is superior to conservative treatment to prevent late postthrombotic sequelae. Protein C, protein S and plasminogen were assayed in 40 DVT patients to determine the incidence of hypercoagulable state in DVT. Congenital deficiency or abnormality were found in 15 patients (37.5%). In such DVT patients with thrombophilia anticoagulant prophylaxis should be continued to decrease a risk of rethrombosis.
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PMID:[The treatment of choice in deep vein thrombosis of the lower extremity]. 147 Jan 17


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