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)

Childhood ischemic stroke, including arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT), is relatively rare in children but can result in devastating morbidity and mortality. An understanding of the etiology of childhood stroke is important because strategies for primary and secondary prevention can be devised. Prothrombotic disorders may contribute to the etiology of childhood stroke, and include deficiencies of antithrombin, protein C, protein S, plasminogen, and presence of Factor V Leiden, Prothrombin gene G20210A, dysfibrinogenemia, antiphospholipid antibodies, hyperhomocysteinemia, and elevated lipoprotein (a). The overall incidence of prothrombotic disorders in childhood AIS is estimated to be 20% to 50% in most studies and, in childhood SVT, to be 33% to 99%. In addition, hyperlipidemia, polycythemia, iron deficiency anemia, and platelet disorders may result in a prothrombotic state associated with ischemic stroke. The etiologic contribution of these prothrombotic disorders to initial and recurrent stroke has not been clearly defined; however, additional risk factors are usually present in affected children. Given the prevalence of prothrombotic disorders in childhood stroke, and their likely causative role, children with stroke should be screened for prothrombotic disorders. Future prospective and multicenter studies will elucidate the contribution of specific prothrombotic disorders to initial and recurrent stroke, and optimal therapy.
 ...
PMID:Prothrombotic disorders and ischemic stroke in children. 1120 19

Homocysteine is an amino acid that is capable of disturbing the proper growth of cells. Hyperhomocysteinemia can lead to a non-closure of the neural tube. The underlying basis is a derangement of homocysteine metabolism due to a missense mutation of the MTHFR enzyme that has to catalyze the folate metabolic cycle furnishing sufficient methyl groups for DNA and tRNA synthesis. Folate can overcome the dysfunction of the mutation and the decreased activity of the thermolabile MTHFR. Homocysteine is also recognized as an independent risk factor for obstetrical vascular disease that can manifest itself in maternal veins (thrombosis), arteries (preeclampsia) or spiral arteries supplying the placenta (placental abruption). Low vitamin status (folic acid, vitamin B6 and B12), hyperhomocysteinemia, the MTHFR gene mutation C677T, and thrombotic factors like Protein C, Protein S. antithrombin III, factor V Leiden and Activated Protein C, are alone or in combination high risk factors for obstetrical vascular disease. Their values can be modulated by B-vitamin status and could be able to prevent disease from occurring or recurring. Placebo-randomized trials have been done in neural tube defects but are urgently needed in the vascular area. The common denominator of the effect of homocysteine on the embryo and the blood vessels (endothelium) could be sited in the process of proliferation of cells that need proper methyl groups for proper function.
 ...
PMID:Homocysteine and human reproduction. 1121 39

Congenital and acquired thrombophilias are the most common predisposing factors for thromboembolism, but they may also contribute to pathophysiological processes involved in recurrent pregnancy loss, fetal death, intrauterine growth restriction, placental abruption, placental infarction, and pre-eclampsia. The most common thrombophilias are deficiencies of antithrombin III, protein C, and protein S, acquired protein C resistance, genetic mutation encoding for factor V Leiden, prothrombin gene, and inherited hyperhomocysteinemia, and antiphospholipid syndrome. Although adverse pregnancy outcomes are more common in women with thrombophilia, the current evidence does not support routine thrombophilia screening of all pregnant women. Selective thrombophilia screening may be justified in certain group of women, particularly those with a history of thromboembolism. More research is required to confirm or refute the causal link between thrombophilia and abnormal placentation, and assess effectiveness and safety of thromboprophylaxis in pregnant women.
 ...
PMID:Thrombophilia and adverse pregnancy outcome. 1125 34

Placental abruption is due to the rupture of the uterine spiral artery. The placenta separates totally or partially from the uterine wall during pregnancy. This serious syndrome has a great risk for the mother (shock and disseminated intravascular coagulation) and her child (mortality or morbidity). To the known risk factors like hypertension, the use of cocaine and smoking, homocysteine is recognized as an independent risk factor for vascular disease and endothelial dysfunction. In contrast to normal pregnancy where the spiral artery endothelium is replaced by trophoblast, the endothelium persists in case of placental abruption. In 165 women with placental vasculopathy and 139 matched controls hyperhomocysteinemia resulted in an odds ratio of 4.7 (95% CI: 1.6-14.0). The C677T mutation gave a risk of 2.5 (95% CI: 1.0-6.0). Even up to 2 or 3 years post-partum evidence could be found of endothelial dysfunction. The combination of hyperhomocysteinemia and thrombotic factors like APC resistance, Protein-C, Protein-S, antithrombin and factor V Leiden increases the risk of placental abruption 3-7 times. The common denominator of the effect of homocysteine on blood vessels could be sited in the process of proliferation of cells that need proper methyl groups for proper function (DNA synthesis and expression). These methyl groups are delivered by D-adenosylmethionine formed from methionine after remethylation of homocysteine. The coagulation factors and plasma homocysteine values can be modulated by vitamins, folic acid and folates in particular. To prove the clinical value of folate supplementation placebo-randomized trials are urgently needed: for placebo to be started after the period of neural tube closure.
 ...
PMID:Clotting disorders and placental abruption: homocysteine--a new risk factor. 1130 Nov 73

Venous thrombosis is a cause of considerable morbidity and is often responsible for chronic venous disorders that frequently lead to visits to dermatologists and others involved in wound healing. Over the past several years, many new causes of thrombophilia have been identified and have dramatically altered the approach to patients presenting with thrombosis. Newly described abnormalities associated with thrombophilia include the syndrome of activated protein C resistance, the prothrombin 20210A mutation, hyperhomocysteinemia, and elevated levels of coagulation factors VIII and XI. Clinicians can now frequently determine causes of thromboses that have previously been deemed idiopathic.
 ...
PMID:An update on hypercoagulable disorders. 1187 42

Effective and safe methods of preventing venous thromboembolism (VTE) are now widely available, but a significant proportion of patients develop VTE either because thromboprophylaxis has not been used or because the intensity of thromboprophylaxis is not matched to the level of risk. Thromboembolic risk varies widely according to the clinical setting and presence of underlying risk factors, but VTE may not be suspected even in high-risk patients. Clinical risk factors for VTE include recent surgery, cancer, stroke, previous VTE, immobilization, and advanced age. Recent attention has focused on the role of inherited and acquired molecular factors in determining overall thromboembolic risk. These factors include the classic thrombophilias-deficiencies of antithrombin III, protein C, and protein S-and several newly described molecular risk factors: factor V Leiden, the prothrombin 20210A gene mutation, and hyperhomocysteinemia. Based on emerging knowledge of risk factors, several risk assessment models (RAMs) have been devised that stratify patients according to overall VTE risk, allowing thromboprophylaxis to be tailored appropriately. Compared with older risk assessment formulas, current RAMs are simpler and include specific recommendations for thromboprophylaxis based on the available scientific evidence. Consensus documents on VTE prevention classify patients into low-, moderate-, and high-risk categories. More recently, a new risk group, very high risk, has been described. Very-high-risk patients are especially prone to thromboembolic complications and need intensive and in some cases prolonged thromboprophylaxis.
 ...
PMID:Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease. 1144 39

Elevated plasma homocysteine is a new risk factor for atherosclerotic vascular disease resulting in progressive atherogenesis in the arteries of the limbs, the coronary arteries and the cerebrovascular system. Hyperhomocysteinemia may be induced by failure or decreased enzyme activity of the cystathionine-beta-synthase and methylenetetrahydrofolate reductase due to genetic mutation or deficiency of folic acid, vitamin B12 and vitamin B6. Oxidation of homocysteine to homocystine is accompanied with production of hydrogen peroxide inducing damage of endothelium through oxidative stress. The injury of the endothelium by homocysteine can be shown by measuring flow-induced vasodilation in men. The abnormalities of coagulation found in hyperhomocysteinemia is related to the impairment of the function of endothelial cells and inhibition of the thrombomodulin-protein C and glycosaminoglycan-antithrombin-III anticoagulant system. Homocysteine decreases the level of glutathione peroxidase in the endothelial cells, and inhibits its activation leading to the impairment of oxidative defensive mechanism, and to the free radical-induced NO-inactivation. In decreasing of plasma homocysteine level and preventing its influence on endothelium, moreover in improving of endothelial function the folic acid has cardinal importance, however the vitamin B12 and vitamin B6 also play role in the maintenance of normal homocysteine level of blood.
 ...
PMID:[Homocysteine--a risk factor for atherosclerosis]. 1148 6

Until recently, laboratory diagnosis of thrombophilia was based on investigation of the plasmatic anticoagulant pathways to detect antithrombin, protein C, and protein S deficiencies and on the search for dysfibrinogenemia and anti-phospholipid antibodies/lupus anticoagulants. More recently, laboratory investigations have been expanded to include activated protein C (APC) resistance, attributable or not to the presence of the factor V Leiden mutation; hyperprothrombinemia attributable to the presence of the prothrombin gene mutation G20210A; and hyperhomocysteinemia attributable to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiencies. All of the above are established congenital or acquired conditions associated with an increased risk of venous and, more rarely, arterial thrombosis. Testing is recommended for patients who have a history of venous thrombosis and should be extended to their first-degree family members. Because most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of treatment. Whenever possible, testing should be performed by means of functional assays. DNA analysis is required for the prothrombin gene mutation G20210A. Laboratory diagnosis for anti-phospholipid antibodies/lupus anticoagulant should be performed by a combination of tests, including phospholipid-dependent clotting assays and solid-phase anti-cardiolipin antibodies. Hyperhomocysteinemia can be diagnosed by HPLC methods or by fluorescence polarization immunoassays.
 ...
PMID:Laboratory investigation of thrombophilia. 1151 92

Authors discussed the known risk factors of venous thromboembolism (VTE), which is complex disease with two manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Acquired risk factors of VTE are following: age over 40 years, bed rest, surgery, trauma, cancer, myocardial infarction, ischemic stroke, use of oral contraceptives, hormone-replacement therapy, pregnancy and puerperium, previous VTE, long lasting travel and presence of antiphospholipid antibodies. Group of genetic defects predisposing to thromboembolic events are called thrombophilia. The best known causes of thrombophilia are: resistance to activated protein C (factor V Leiden), the prothrombin 20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and abnormality in the fibrinolytic system. Genetic predisposition to thrombosis may be detected in up to one-third of patients with VTER and more than 50% of patients with familial thrombosis. Detection of factor V Leiden is important for patients: with recurrent incidences of VTE, with other known causes of thrombophilia and in members of families with frequent occurrence of VTE. It is important also to detect deficiency of: protein C, protein S and especially of antithrombin in patient with previous VTE, because such patients have 8 to 10 fold increase risk of next incident of VTE. Chronic prevention of thrombosis should be used in all these cases.
 ...
PMID:[Risk factors of venous thromboembolism]. 1155 14

Few and contrasting data are available on the prevalence of hemostatic risk factors in patients with central retinal vein occlusion (CRVO). Aim of this study was to investigate the metabolic and inherited risk factors for venous thrombosis in 100 CRVO patients (age: 59 yrs; range 18-77) and in 100 controls (age: 56 yrs; range 18-84). In patients homocysteine (Hcy) levels were significantly higher than in controls and were affected by the C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism (p < 0.001). The prevalences of activated protein C resistance (APCR), factor V Leiden positivity, elevated PAI-1 and Lp(a) levels were significantly higher in patients with respect to controls. At multivariate analysis, only hyperhomocysteinemia (OR 11, 95% CI 3.6-36.2; p < 0.0001) and elevated PAI-1 levels (OR 8.9, 95% CI 3.5-41.3; p < 0.01), in addition to hypertension (OR 40.5, 95% CI 8.6-188.8; p < 0.00001) and hypercholesterolemia (OR 3.1, 95% CI 1.6-20.5; p < 0.05), were independent risk factors for CRVO. These data demonstrate a potential role of hemostatic risk factors in the pathophysiology of CRVO.
 ...
PMID:Thrombophilic risk factors in patients with central retinal vein occlusion. 1208 91


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