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

The antiphospholipid syndrome is defined as the association between the presence of antiphospholipid antibodies, detected as anticardiolipin antibodies and/or lupus anticoagulant, and a history of either arterial or venous thrombosis and/or recurrent pregnancy loss. Because thrombosis may occur in virtually any organ system, diagnosing the antiphospholipid syndrome and taking appropriate anticoagulation measures are important considerations in all medical specialties. Antiphospholipid antibody-associated thrombosis tends to recur. Antithrombotic prophylaxis to prevent recurrences is therefore needed. Prophylaxis in individuals with circulating antiphospholipid antibodies who have no history of thrombosis is still controversial. Although direct evidence for a pathogenetic role of antiphospholipid antibodies in the development of thrombosis is still lacking, recent studies suggest that it is causative rather than coincidental. New insights on the possible mechanisms leading to thrombosis were provided by the discovery of the serum cofactor (beta2-GPI), a coagulation inhibitor which is required for binding of anticardiolipin antibodies to cardiolipin. More recently, patients with antiphospholipid antibodies were found to possess autoantibodies directed against other coagulation factors, including prothrombin, protein C and protein S. Future studies should clarify whether these different antigenic specificities are associated with particular clinical events and assess the risk of thrombosis associated with the presence of antiphospholipid antibodies in asymptomatic individuals.
 ...
PMID:The clinical significance of antiphospholipid antibodies. 918 33

The prevalence of haemostasis abnormalities was evaluated in 500 consecutive women with unexplained primary recurrent miscarriages. Two matched reference groups with no antecedent of miscarriage were studied: 100 healthy mothers and 50 childless women. In the prospective part of the study, we found 9.4% of the patients (95% C.I.: 6.8-12%) with an isolated factor XII deficiency, 7.4% of the patients (5.0-9.8%) with primary antiphopholipid antibodies, 47% of the patients (42.6-51.4%) with an insufficient response to the venous occlusion test and an isolated hypofibrinolysis was found in 42.6% (38.2-47%) of the patients (reference groups: respectively 0/150, 3/150, 2/150, p < 10(-3)). Willebrand disease, fibrinogen, deficiency, antithrombin, protein C or protein S deficiencies were not more frequent in recurrent aborters than in members of the reference groups. In the retrospective part of the study, cases of plasma resistance to activated protein C were not abnormally frequent. Patients had higher Willebrand factor antigen (vWF), tissue-type plasminogen activator antigen (t-PA), plasminogen activator inhibitor activity (PAI) and D-dimers (D-Di) than the reference women. Values of vWF, t-PA, PAI and D-Di were altogether correlated but were not related to C-reactive protein concentrations. Among patients, those with an antiphospholipid syndrome and those with an insufficient response to the venous occlusion test had higher vWF, t-PA, PAI and D-Di values than the patients with none of the haemostasis-related abnormalities. Thus, factor XII deficiency and hypofibrinolysis (mainly high PAI) are the most frequent haemostasis-related abnormalities found in unexplained primary recurrent aborters. In patients with antiphospholipid antibodies or hypofibrinolysis, there is a non-inflammatory ongoing chronic elevation of markers of endothelial stimulation associated with coagulation activation. This should allow to define subgroups of patients for future therapeutic trials.
 ...
PMID:Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study. 924 39

Recurrent fetal loss and other placental vascular pathologies of pregnancy have long been associated with antiphospholipid syndrome-an acquired autoimmune thrombophilic state. The number of known heritable thrombophilic disorders has grown rapidly in recent years with the identification of activated protein C resistance, factor V Leiden mutation and hyperhomocysteinemia as major causes of thrombosis. Data accumulated over the past two years suggest that heritable thrombophilia is associated with increased risk of fetal loss and pre-eclampsia. The present review discusses potential pathogenetic mechanisms for this association and evaluates reported therapeutic regimes for the prevention of fetal loss in women with thrombophilia.
 ...
PMID:Thrombophilia and fetal loss. 924 90

Thromboembolic disorders are frequent complications in pediatric patients and the incidence seems to rise. Adult guidelines for thromboembolism do not hold for children because there are many age-related features. Congenital prethrombotic disorders play a major role in the pediatric population and activated protein C (APC) resistance is also the most frequently encountered problem. Acquired risk factors in children are central venous line thrombosis with serious complications, cardiac diseases such as cardiomyopathies, prosthetic heart valves and aneurysms, renal vein thrombosis, and nephrotic syndrome. Renal vein thrombosis primarily affects newborns. Children with the antiphospholipid antibody syndrome also have thromboses although less frequent than adults, but systemic lupus erythematosus is associated with a high incidence. Acute lymphoblastic leukemia is frequently associated with thrombosis in children, especially when complicated by APC resistance. The greatest risk of thrombosis in children is during the neonatal period, and again congenital prethrombotic states and catheter placement play a major role. The clinical manifestations in children reflect the site of the thrombosis and extensive laboratory evaluations and advanced diagnostic procedures must be employed to diagnose the thrombotic events.
 ...
PMID:Diagnosis of thromboembolic disease during infancy and childhood. 925 4

Evaluation of inherited hypercoagulability in patients with venous thromboembolism includes testing for the functional activity of protein S, protein C, antithrombin III, and for resistance to activated protein C. Resistance to activated protein C can be assessed with plasma as well as with DNA-based assays that are commercially available. Acquired disorders include the development of antibodies against phospholipid-protein complexes (as would occur in patients with the antiphospholipid syndrome). The inherited and acquired abnormalities are most commonly apparent as superficial or deep venous thromboembolism in younger patients, most of whom have additional risk factors for thrombosis, such as use of oral contraceptives or recent trauma. These tests are cost effective if the results will influence patient management or will have potential value in the care of family members in situations of increased thrombotic risk.
 ...
PMID:Laboratory testing for hypercoagulable disorders. 937 3

The antiphospholipid antibodies (APA) are acquired antibodies against a phospholipid which has been associated with slow progressive thrombosis and infarction in the placenta. Clinical features (venous or arterial thrombosis, recurrent fetal loss, thrombocytopenia) in conjunction with positive laboratory findings (positive IgG or IgM anticardiolipin antibodies, or positive lupus anticoagulant tests) will satisfy criteria for diagnosis of the antiphospholipid antibody syndrome (APS). A number of studies report the incidence of antiphospholipid antibodies in different patient populations: normal obstetrical patients (5.3% of 7278 women), women with recurrent pregnancy loss (20% of 2226 women), women with systemic lupus erythematosus (37% of 1579 women) and, more recently, women undergoing in vitro fertilization (24% of 3343 women). As in all autoimmune syndromes it is possible that APA are secondary to some underlying disease or that they are instrumental in the pathogenesis of the various manifestations. The most commonly proposed mechanisms of antiphospholipid antibody induced thrombosis include decreased prostacycline production by endothelial cells, increased thromboxane production by platelets, and decreased protein C activation. More recently it has been demonstrated that certain phospholipids are exposed on the endothelial surface and may alter implantation during in vitro fertilization. Treatment with subcutaneous heparin and aspirin has been shown to benefit women with recurrent pregnancy loss and APA resulting in successfully deliveries of approximately 75%. Several trials of treatment with heparin and aspirin in women with positive APA undergoing IVF have been completed. Although none of the studies were randomized, prospective, blinded trials there does not appear to be a significant difference in implantation rate, pregnancy rate, or ongoing pregnancy rate. This subject remains, however, an area of active investigation as antiphospholipid antibodies have been shown to interact with syncytiotrophoblast and cytotrophoblast layers and could theoretically affect implantation.
 ...
PMID:Antiphospholipid antibodies and reproduction. 942 98

To investigate the possibility that activated protein C (APC) resistance due to the factor V could be an important predisposing factor in acute myocardial infarction (AMI), we have retrospectively examined the prevalence of APC resistance with protein C, protein S and antithrombin III deficiency and antiphospholipid antibody syndrome in AMI patients (< or = 50 years) admitted to our hospital over the past 7 years. Forty-seven patients were enrolled in the study. We divided the patients into two groups, warfarin group (group A) and a non-warfarin group (group B). APC resistance is defined as when the APC ratio is below or equal to the cut-off value 2. APC resistance was not detected in either group. The prevalence of an APC ratio below or equal to 2.5 was 16.7% (1 case) in group A and 24.4% (10 cases) in group B. The prevalence of protein C deficiency was 5.0% (2 cases) in group B. Two cases (5.0%) in group B had protein S deficiency. Antithrombin III deficiency was not detected in either group. The prevalence of antiphospholipid antibody syndrome measured by APTT was 40.4% (19 cases). We compared the AMI patients with 97 healthy volunteers (< or = 50 years old) without any thromboembolic events or bleeding tendency in their past history. No significant difference were found between these groups and the volunteers. APC resistance is a major cause of venous thromboembolism in Europe and the United States, while in Japan it is believed to be a minor cause of arterial thromboembolism.
 ...
PMID:Prevalence of activated protein C resistance in acute myocardial infarction in Japan. 948 29

Blood coagulation tests are useful to diagnose some thrombotic diseases. Particularly, these tests are valuable for the diagnosis of familiar thrombophilia, antiphospholipid antibody syndrome (APS) and disseminated intravascular coagulation (DIC). For the diagnosis of thrombophilia, determinations of both biological activity and antigen level of antithrombin III, protein C and protein S are important for initial screening. Since activated protein C (APC) resistance is extremely rare in Japanese, APC resistant test that based on APTT, is unnecessary to include as one of the screening tests. Detection of activity and antigen level of either plasminogen or fibrinogen is recommended to screen the plasminogen deficiency or dysfibrinogenemia. Determination of lupus anticoagulant is needed for the diagnosis of APS. At this time, the dilute phospholipid APTT (dAPTT) or the dilute Russell viper venom time (dRVVT) may be useful as a screening test for LA because procedure of these tests are basically simple to perform in Japanese laboratory. In the next step, cross mixing test of dAPTT (or APTT) should be perform to make a diagnose of LA more solid. Final confirm tests can be conveniently carried out with kit of either STACLOT or LA-CONFIRM. Platelet count and FDP (or FDP D dimer) assay are two essential tests for the diagnosis of DIC. Criteria of diagnosis for DIC recommended by Blood Coagulation Research Group of Japanese Ministry of Health and Welfare is not unnecessarily appropriate for practical use. TAT and PIC can be a good laboratory tests for early detection of hypercoagulable state in patients with DIC.
 ...
PMID:[Clinical diagnosis of thrombosis and blood coagulation tests]. 956 63

The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder in which thromboembolism and thrombocytopenia occur. The antiphospholipid antibodies in these patients may cause acquired activated protein C resistance, whereas hereditary activated protein C resistance results from a common single point mutation in coagulation factor V (factor VLeiden). In a family of 11 members with 4 normal subjects, autoimmune thrombocytopenia was documented in 6 patients. Three out of these were found to have thrombocytopenia associated with primary APS. In addition, these 3 subjects were also heterozygous for the factor VLeiden. Only in this group of individuals did life threatening thromboembolic complications occur, while other thrombocytopenic family members showed no thrombotic manifestations. Genetic studies revealed no linkage between APS and HLA class II alleles. Taken together, we present a family with autoimmune thrombocytopenia, which is associated with primary APS in at least 50% of thrombocytopenic individuals. The coexistence of both APS and factor VLeiden in thrombocytopenic subjects, led to an increased number of thrombotic events, suggesting a critical role of combined acquired and hereditary activated protein C resistance in the development of thrombosis in this family. Since no association between APS and specific HLA groups was found, other underlying risk factors for the development of APS must be considered.
 ...
PMID:Familial coexistence of primary antiphospholipid syndrome and factor VLeiden. 960 41

It is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via beta2-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of beta2-GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of beta2-GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and beta2-GPI, but binding was not found in the absence of beta2-GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of beta2-GPI and that of anti-beta2-GPI antibody (r = 0.802, P = 0.0001). We further analysed the interaction between protein C, phospholipids, beta2-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of beta2-GPI to protein C and its phospholipid dependency were investigated. Beta2-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of beta2-GPI (virtually anti-beta2-GPI antibodies) was evaluated in the presence of cardiolipin and beta2-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and beta2-GPI, whereas they did not in the absence of either beta2-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and beta2-GPI, leading to protein C dysfunction.
 ...
PMID:Binding of anticardiolipin antibodies to protein C via beta2-glycoprotein I (beta2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system. 964 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>