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)

To investigate whether resistance to activated protein C (APC resistance) because of a mutation in the factor V gene (factor V Leiden) leads to a decrease in life expectancy, we analyzed overall and cause-specific mortality in 171 parents whose offspring carried this mutation. Compared with the Dutch general population, and after adjustment for age, sex, and calendar period, we found no excess deaths in the parents (standardized mortality ratio [SMR], 1.0; 95% confidence interval [CI], 0.8 to 1.2). The cause-specific SMR for malignant neoplasms (1.0; 95% CI, 0.6 to 1.4), diseases of the circulatory system (1.0; 95% CI, 0.7 to 1.4), and cerebrovascular disease (1.0; 95% CI, 0.4 to 1.9) also did not differ from unity. The SMRs for diseases of the respiratory system (1.4; 95% CI, 0.6 to 2.6) and for ischemic heart diseases (1.1; 95% CI, 0.7 to 1.7) were slightly increased. Under the age of 45 years, there was a ninefold increase of dying from ischemic heart disease. Thromboembolic complications were mentioned only once (venous embolism or thrombosis) as an underlying ("primary") cause of death (SMR, 2.3; 95% CI, 0.1 to 13.0) and three times (pulmonary embolisms) as a contributing ("secondary") cause of death (SMR, 1.5; 95% CI, 0.3 to 4.4). We conclude that there is no major effect of APC resistance on life expectancy. Therefore, long-term anticoagulation in carriers of factor V Leiden, on the basis of the carrier state alone, is not indicated.
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PMID:Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). 905 17

We estimated the predictive values of activated protein C resistance in the diagnosis of women who are carriers of factor V Leiden. When the prevalence of factor V Leiden is 2%, the positive predictive value is 44% and the cost of preventing one thromboembolic death is $44,180,000. Thus the activated protein C resistance assay is not cost-effective in ruling out factor V Leiden in this population.
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PMID:Activated protein C resistance assay when applied in the general population. 939 30

The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to increased resistance to APC, which in turn may contribute to the vaso-occlusive complications of SS disease.
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PMID:Activated protein C resistance in homozygous sickle cell disease. 907 31

The aim of the study is to determine if a novel thrombophilia mechanism (factor V Leiden) that is associated with resistance to activated protein C (APC) is in itself a risk factor for the development of ischemic stroke (IS). Sixty-six controls and 66 patients with IS were included in an unmatched case-control study. In the group of patients selected for this study, other causes of IS were ruled out. APC resistance was considered if activated partial thromboplastin time (aPTT) measured in the presence of APC was less than 2.2 times prolonged when compared to aPTT in the absence of APC (APC ratio < 2.2). Digestion with a restriction enzyme of a previously amplified exon 10 of the gene that encodes for factor V was used to detect the presence of the factor V mutation. We identified 5 patients (prevalence: 7.5%) with APC resistance (mean age: 31 years, range: 6-52 years). Mutation in factor V gene was confirmed in three of them. In the control group we detected 3 (4.5%) low APC ratios, all of them carrying specific factor V mutation. We cannot conclude a significant association between APC resistance and IS [odds ratio: 1.72; chi 2 Mantel and Haenszel was 0.53 (p = 0.4673) and exact Fisher's test p = 0.3589] but these 5 young adults suffered an episode of IS having APC resistance as the only prothrombotic condition. In conclusion, these results cannot prove a statistical association between APC resistance and IS. Further studies must be done in order to confirm that there is no relationship between APC resistance and IS in young adults when major risk factors are excluded.
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PMID:Low prevalence of the factor V Leiden among patients with ischemic stroke. 909 81

We investigated the role of the thrombomodulin (TM/protein C/protein S anticoagulant pathway in modulating the thrombogenic properties of the endothelium. Endothelial cells (ECs) were placed in parallel-plate flow chambers and exposed to nonanticoagulated human blood at a venous wall shear rate (50 s-1). Fibrin deposition on resting ECs treated with a control IgG1 was negligible. In contrast, a significant amount of fibrin deposited when TM expression was specifically suppressed by > 95% by preincubating ECs with an anti-TM IgG1. Similarly, fibrin deposited on interleukin 1-stimulated ECs, but the fibrin deposition was further increased threefold with anti-TM IgG1. Comparable results were found when ECs were perfused at 650 s-1. When TM surface activity was enhanced by 150% by treating ECs with active phorbol ester (4-phorbol 12-myristate 13-acetate; PMA), the deposition of fibrin was 30% lower than on ECs not pretreated with PMA. Finally, fibrin deposition on stimulated ECs was significantly higher in 11 untreated patients with well-characterized deficiencies of protein C or S or heterozygous factor V Leiden mutation than in 11 healthy individuals, and it was significantly correlated to basal plasma levels of thrombin-antithrombin complexes. Thus, this study underlines the central role of the TM/protein C/protein S pathway in modulating the thrombogenic status of resting and stimulated ECs and indicates that basal coagulation system markers may be helpful in monitoring patients presenting a disorder of this anticoagulant pathway.
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PMID:The thrombomodulin/protein C/protein S anticoagulant pathway modulates the thrombogenic properties of the normal resting and stimulated endothelium. 910 71

Factor V Leiden (factor V Arg506Gln), the genetic defect underlying resistance to activated protein C, is the most common risk factor for venous thrombosis. The relationship between this genetic abnormality and arterial disease is still unresolved. To assess whether factor V Leiden increases the risk of myocardial infarction (MI), we conducted a population-based case-control study among women 18 to 44 years of age in western Washington state. We included 84 women with first MI and 388 control women, ie, women residing in the same area in the same age range without MI (n = 388). The control women were contacted by random digit dialing. Data on risk factor status were collected via personal interview, and data on the factor V genotype via polymerase chain reaction techniques. The factor V Leiden mutation was found more often in women with MI (10%) than among controls (4%). The odds ratio for MI was 2.4 [95% confidence interval (CI) 1.0 to 5.9]. The risk was increased fourfold (CIgs 1.2 to 12.1) when adjusted for major cardiovascular risk factors. Among nonsmokers the factor V Leiden mutation had little effect (odds ratio 1.1, CI95 0.1 to 8.5), whereas it had a large effect among smokers (odds ratio 3.6, CI95 0.9 to 14.4), which, because smoking was itself a strong risk factor for MI, led to an odds ratio for smoking carriers of the mutation that was 32-fold increased compared with nonsmoking noncarriers. We conclude that factor V Leiden increases the risk of MI in young women. This effect seems to be confined largely to current smokers.
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PMID:Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. 929 54

The new progestative molecules have allowed the reduction of the doses of steroids in estroprogestative pills. They have a reduced androgenic activity allowing the positive effects of ethinylestradiol on lipid metabolism with decreased myocardial infarct, ischemic or hemorrhagic stroke. However it is necessary to consider the woman's entire risk factor profile when prescribing oral contraceptives. Unfortunately, combined estroprogestatives containing low-dose estrogen and the progestagens desogestrel or gestodene are associated with an increased risk for nonfatal venous thromboembolic disease. The occurrence of venous thromboembolic disease in a woman with oral contraceptive requires to search for a hereditary abnormality especially a resistance to the anticoagulant effect of activated protein C. Conversely it seems necessary to screen for the factor V Leiden mutation in women starting oral contraceptives who have a history of a familial venous thrombosis story.
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PMID:[The vascular risk of third generation contraceptive pills]. 912 Mar 73

Thromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anti-coagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients, with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% CI 7.8-17) in patients without factor V Leiden and was 10.6% (95% CI 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.
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PMID:The risk of recurrent venous thromboembolism in patients with and without factor V Leiden. 913 32

Blood samples from 104 patients with clinically suspected thrombophilia were analyzed for coagulation factor V Leiden mutation (1691, G-->A) by allele-specific polymerase chain reaction. In 86 individuals (82.7%), the mutation was not detectable, whereas 15 patients (14.4%) were heterozygous and three patients (2.9%) were homozygous for factor V Leiden mutation. Plasma samples from these individuals were also tested for functional resistance of coagulation factor V to activated protein C (activated protein C resistance). This test was performed on a Schnitger-Gross coagulometer using an activated partial thromboplastin time-based activated protein C resistance test modified by applying a 1 : 5 dilution with factor V-deficiency plasma. All the individuals negative for factor V Leiden mutation were also negative in the functional activated protein C resistance test. On the other hand, all patients carrying the mutation revealed pathologic results in the activated protein C resistance test. The cutoff value for the activated protein C resistance index (> or = 1.7 = negative) was determined by testing 31 male and female blood donors. One of them was heterozygous for factor V Leiden mutation and had an activated protein C resistance index of 1.4, whereas those without factor V Leiden mutation had an activated protein C resistance index of 1.9 +/- 0.1 (mean +/- SD). Patients with clinically suspected thrombophilia without factor V Leiden mutation had an activated protein C resistance index of 2.1 +/- 0.2 (mean +/- SD), whereas patients heterozygous for the mutation had an index of 1.5 +/- 0.1 (mean +/- SD). Within the group of patients carrying the mutation, the activated protein C resistance test even distinguished between heterozygous and three homozygous (activated protein C resistance 1.0 to 1.2) carriers. The data demonstrate that the activated protein C resistance test in the presence of factor V-deficiency plasma provides a clear-cut discrimination between normal wildtype and carriers of factor V Leiden mutation with a sensitivity and specificity of 100%. Verification of positive activated protein C resistance tests can be performed easily with a simple and reliable polymerase chain reaction protocol for the 1691, G-->A mutation.
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PMID:Discrimination between normal wildtype and carriers of coagulation factor V Leiden mutation by the activated protein C resistance test in the presence of factor V deficient plasma. 915 66

Portal vein thrombosis (PVT) is a rare condition affecting both children and adults, and occurs in association with a wide variety of clinical situations. On the other hand, the development of PVT in patients under these situations indicates that other contributing factors could be involved. Recently a missense mutation in the factor V gene (1691G-->A), known as factor V Leiden, has been identified and results in abnormal factor V product, resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis. This study was carried out to verify if children with PVT have an increase in frequency of factor V Leiden. Allele-specific restriction analysis and single strand conformational polymorphism (SSCP) were used to test for factor V Leiden in 20 children with PVT and 64 normal children. None of the PVT children were heterozygous or homozygous for the factor V Leiden, and one control child was heterozygous. This study demonstrates that factor V Leiden is not common in children with PVT, and is not a prerequisite for this thrombotic event.
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PMID:Factor V Leiden is not common in children with portal vein thrombosis. 936 3


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