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)

We report a patient with Noonan syndrome and asymptomatic cardiac disease (supravalvular aortic stenosis and pulmonary valvular stenosis) who had frequent transient ischemic attacks. Bilateral moyamoya was evident; in addition, he manifested activated protein C resistance and was heterozygous for the factor V Leiden mutation. Anticoagulation abolished his episodes and, despite extensive cerebrovascular disease, he has no permanent neurologic deficits. The association between Noonan syndrome and moyamoya has not previously been described. Disruption of vascular development in prenatal life may have resulted in both cardiac and cerebrovascular disease in this child.
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PMID:Noonan syndrome and moyamoya. 916 21

While many studies have demonstrated the pathogenetic role of inherited deficiency of natural clotting inhibitors in patients in the development of deep vein thrombosis of lower limbs, no data are available on the prevalence of these abnormalities in patients with upper vein thrombosis. In this study, antithrombin III, protein C, protein S, plasminogen, resistance to activated protein C and factor V Leiden mutation were assayed in 27 consecutive patients with thrombosis of upper extremities. Only two patients (7.4%) showed a congenital defect (one patient with deficiency of protein C, confirmed by family study, and one patient with factor V Leiden mutation). Anticardiolipin antibodies were also measured and four patients (14.8%) had increased levels, confirmed on a subsequent occasion 3 months later. Eighteen out of 27 (67%) had a predisposing or triggering factor, thus emphasizing the role of physical stress in the development of upper vein thrombosis. At variance with what is observed in deep vein thrombosis of the lower limbs, inherited clotting abnormalities seem to be rarely responsible for upper vein thrombosis, whereas anticardiolipin antibodies and cancer are implicated in a significant proportion of cases.
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PMID:Low prevalence of thrombophilic coagulation defects in patients with deep vein thrombosis of the upper limbs. 916 20

Oral contraceptives (OCs) have minor effects on procoagulant and anticoagulant factors. Clotting factor changes that are associated with the use of low-androgenic OCs include a 10% to 20% increase in fibrinogen, variable effects on factor VII, an increase in fibrinopeptide A, and a 10% to 20% decrease in protein S (in comparison, levels of protein S decrease approximately 70% during pregnancy). Although these acquired changes can be statistically significant between OC users and nonusers, there is no evidence that they are clinically significant. In contrast, increased risk of venous thrombosis has been associated with inherited deficiencies in protein S and protein C, which are both natural anticoagulant proteins. In addition, activated protein C (APC) resistance can occur via a mutation of factor V, known as factor V Leiden, which is present in 5% of the general population and 20-40% of patients with venous thrombosis. In one study, the combination of OC use and factor V Leiden positivity was associated with a 35-fold increased risk of venous thrombosis compared with controls. However, the absolute risk of venous thrombosis in this group was low; the incidence of venous thrombosis was 28.5 events per 10,000 women-years in women with both factors (in comparison, pregnancy was associated with an incidence of 5.9 per 10,000 women-years). Even if venous thrombosis could be totally prevented in OC users with the Leiden mutation, there would be little impact on the total number of cases of venous thrombosis; therefore, routine screening for factor V Leiden or APC resistance prior to starting women on OCs does not seem to be warranted.
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PMID:Thrombophilic mechanisms of OCs. 916 76

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
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PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

A case-control study failed to substantiate concerns that first-trimester repeated abortion is associated with activated protein C resistance. In its heterozygous form, activated protein C resistance creates a life-long hypercoagulable state and a 5- to 10-fold increased risk of venous thrombosis. Frozen blood samples from 55 consecutive patients with two or more (mean, 2.9; range, 2-7) consecutive first-trimester spontaneous abortions of unknown etiology were compared to those from 50 healthy blood donors with at least one child but no previous abortion. Mean activated protein C resistance ratio in the 55 cases was 3.2 in the direct test and 2.9 in the modified test. Only one case had phenotypic activated protein C resistance (ratio of 1.4 in the direct test and 1.5 after factor V depleted plasma dilution). Genotype analysis confirmed that this patient, who had two previous abortions at 10 and 8 weeks of gestation, was heterozygous for the factor V Leiden mutation. One woman in the control group had activated protein C resistance phenotype (ratios 1.9 and 1.8 in the direct and modified tests, respectively) that was confirmed as heterozygous for factor V Leiden mutation. The development of resistance to activated protein C is presumed to occur mainly after 14 weeks of gestation and is more evident at term. The findings of this study suggest that factor V Leiden screening in first-trimester repeated abortion is not warranted.
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PMID:First-trimester repeated abortion is not associated with activated protein C resistance. 919 72

In both children and neonates with venous thrombosis, one or more predisposing risk factors can generally be identified. Underlying prothrombotic medical conditions are common in these patients. In addition, a "trigger factor" such as a catheter, surgery or trauma is usually present. However genetic and acquired coagulation abnormalities are also identified in children with venous thrombosis who are appropriately studied. A careful family history and assays for the LA, AT-III, protein C, protein S and the factor V Leiden mutation should be part of the evaluation of infants and children with venous thrombosis.
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PMID:Disorders of hemostasis in childhood: risk factors for venous thromboembolism. 919 44

Factor V antigen levels were measured in 40 patients with factor V deficiency (11 homozygous and 29 heterozygous), in 38 patients with factor V Leiden mutation (16 homozygous and 22 heterozygous) and in three patients with combined heterozygous factor V deficiency and heterozygous factor V Leiden mutation (so-called pseudohomozygosis for APC resistance). Twenty normal subjects of both sexes served as controls. Factor V antigen levels compared well with factor V activity in normal subjects and in all groups of patients. They were normal both in homozygous and heterozygous APC resistance patients. Factor V antigen determination may be useful for the diagnosis of pseudohomozygosis for APC resistance. These patients have a phenotypic picture similar to homozygous APC resistance, but show a factor V antigen level about half the normal value since they are compound heterozygotes for factor V deficiency and APC resistance. In contrast, homozygous patients for APC resistance show normal factor V activity and antigen levels.
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PMID:Factor V antigen levels in APC resistance, in factor V deficiency and in combined APC resistance and factor V deficiency (pseudohomozygosis for APC resistance). 919 22

Over the last four years, there has been an explosion of knowledge about APCr and factor V Leiden. However, there remain a considerable number of difficult clinical areas in which there are no clear answers. Undoubtedly, factor V Leiden is commonly found in association with venous thromboembolic disease in whatever manifestation, but equally it has an unusually high frequency in the general population. Only a small proportion of those that carry the mutation develop a thrombosis. It is estimated that only 6% of those that carry the mutation will develop a thrombosis over a 30-year period, whilst for antithrombin, Protein C or Protein S deficiency, this figure is nearer 60%. Particular areas of difficulty remain in relation to the use of the combined OCP and in the management of the asymptomatic carrier of the mutation in pregnancy. Although the scientific basis of APCr and factor V Leiden is well established, its natural history remains relatively poorly understood, probably as a consequence of its relative novelty. Despite the plethora of new data that have appeared, there remains much to be learnt about factor V Leiden and the APCr phenotype.
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PMID:Resistance to activated protein C and factor V Leiden. 920 75

As thrombosis of placental vessels may result in recurrent fetal loss, we analysed 39 consecutive women with recurrent fetal loss of unknown cause for activated protein C resistance. Factor V Leiden (FVL) mutation (19 cases) or APC resistance without FVL (nine cases) were found among these 39 women. Evaluation of 128 pregnancies in 19 patients with factor V Leiden mutation and 56 gestations in nine women with acquired APC resistance, revealed over 50% first-trimester abortions and 17% late abortions. Intra-uterine fetal death occurred in nine out of 19 FVL patients (47%). Only 34 of 184 gestations (18%) in hereditary or acquired APC-resistance women resulted in a live birth, with 11 of the 34 (32%) being premature deliveries. These data suggest that, in some patients with recurrent fetal loss, hereditary and acquired APC resistance are potential causes of vascular placental insufficiency.
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PMID:Activated protein C resistance can be associated with recurrent fetal loss. 920 98

Activated protein C resistance caused by factor V Leiden is an important thrombophilia disorder which predisposes to venous thromboembolism. Some studies also suggest a role in the pathogenesis of arterial thrombosis and atherosclerosis. The authors have investigated the prevalence of activated protein C resistance and factor V Leiden in a series of 45 patients with peripheral vascular disease. Twelve patients were receiving warfarin. The activated protein C resistance ratios were significantly lower in the group of 33 non-warfarinized patients with peripheral vascular disease (median 2.82 (range 1.36-3.83)) compared with 33 age- and sex-matched controls (median 2.97 range 2.24-4.11); P<0.005; Wilcoxon rank sum). Eight patients (24%) had activated protein C resistance (ratio <2.2). The prevalence of factor V Leiden in patients with peripheral vascular disease was 17.8% (8/45). This is significantly increased compared with the local population and UK published frequency of 3.5% for this genotype. The presence of factor V Leiden did not affect the late outcome of arterial reconstructive surgery in terms of graft patency (P=0.5, Fisher's Exact test).
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PMID:Activated protein C resistance, factor V Leiden and peripheral vascular disease. 921 1


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