Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent discovery of the factor V Leiden mutation as the molecular defect in the large majority of APC-resistant individuals, has drastically changed our view on familial thrombophilia and it has contributed to a better understanding of the interaction of genetic and environmental risk factors. It has offered firm support for the view that venous thrombosis is a multifactorial disease and that the risk of thrombosis will increase as the number of genetic and/or environmental risk factors increases.
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PMID:Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. 857 4

Resistance to activated protein C (APC resistance) due to the factor V mutation 506 Arg-->Gln (factor V Leiden) is the most prevalent inherited risk factor for venous thromboembolism. Its association with arterial thromboembolic disease, however, is still controversial. In the present study we found no difference between the prevalence of APC resistance (assessed by the ratio of the aPTT with and without added APC) in 134 non-anticoagulated survivors of myocardial infarction and that in 100 controls of similar age and sex distribution (2.2% and 2.0%, respectively). Patients showed a significantly higher median value for the aPTT ratio than controls (2.85 and 2.66, respectively), a fact we could not explain by our data.
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PMID:No association of APC resistance with myocardial infarction. 858 13

Resistance to activated protein C (APCR), in the majority of cases due to the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of venous thromboembolism. Using an activated thromboplastin time (aPTT) based method in the presence of APC together with a DNA technique based on the polymerase chain reaction, we investigated 37 children with venous (V: n=19) or arterial (A: n=18) thromboembolism and 196 age-matched healthy controls for the presence of this mutation. In the control group 10 children were detected to be heterozygous for the factor V Leiden mutation, indicating a prevalence of 5.1%. 10/19 children (52%) with venous thrombosis and 7/18 (38%) patients with arterial thromboembolism showed the common factor V gene mutation. Additional inherited coagulation disorders were found in 1/10 (V:10%) and 2/7 (A:28%) APC-resistant patients. Inherited coagulation disorders without APCR were diagnosed in 3/9 (V: 33%) and 2/11 (A:18%) children. Furthermore, we diagnosed exogenous risk factors in 6/10 (V: 60%) and 2/7 (A: 28%) children with thrombosis and APCR. These data are evidence that APCR combined with exogenous reasons may play an important role in the early manifestation of thromboembolism during infancy and childhood.
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PMID:Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism. 1036 46

Resistance to the anticoagulant effect of activated protein C (APC resistance), a frequent abnormality in patients with a history of venous thrombosis, is known to be due, in the large majority of cases, to the presence of an abnormal factor V: the factor V Leiden. It is reasonable to surmise that screening for this abnormality should be performed with a clotting method for APC resistance, before submitting the patients with abnormal results to DNA analysis. The present study was performed on 216 individuals enrolled at the Bologna centre, of which 189 were unrelated patients with a history of juvenile venous thromboembolism and 27 were relatives with or without thrombosis. APC resistance was first measured in Bologna by a standard commercial method and then, in Leiden, by an in-house method: DNA analysis was performed in those cases in which at least one of the clotting methods was abnormal. The data obtained confirm the good performance and the optimal positive predictive value for the Leiden mutation (100%) of the Leiden in-house clotting method. Performance of the commercial method was less satisfactory but markedly improved by expressing the data in relation to the values simultaneously obtained with a normal plasma pool. Even with optimal data expression, however, the positive predictive value of the commercial method, versus DNA analysis, did not exceed 88%. It is concluded that further standardization of the commercial method here evaluated is necessary before it can be widely adopted for the screening of APC resistance and prediction of the presence of factor V Leiden.
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PMID:Activated protein C resistance: a comparison between two clotting assays and their relationship to the presence of the factor V Leiden mutation. 890 5

A point mutation in the factor V gene (factor V Leiden) is the most common cause of familial thrombophilia. Patients with factor V Leiden have an increased risk of thrombosis, particularly those homozygous for the mutation. However, the phenotype in individuals with the mutation is variable, suggesting that other factors influence thrombotic risk. We describe for the first time a family in which two independent defects in factor V co-exist: heterozygosity for factor V Leiden and factor V deficiency. Compound heterozygosity for these two defects results in a phenotype similar to a homozygous factor V Leiden state with profound resistance to APC and recurrent thrombosis.
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PMID:Recurrent thrombosis due to compound heterozygosity for factor V Leiden and factor V deficiency. 873 45

Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.
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PMID:APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method. 887 45

APC resistance is a common and strong hereditary risk factor for venous thrombosis. This plasma abnormality appears to be almost always caused by the same defect in the coagulation factor V gene (a G --> A transition at nucleotide 1691 leading to replacement of 506 Arg by Gln; factor V Leiden). Therefore, it is possible to consider a simple and specific genetic test as an alternative to a plasma APC resistance test that is compromised by treatment and other factors. We have investigated whether a new amplification procedure, NASBA, together with the detection procedure ELGA would provide a simple protocol for the nucleotide specific detection of the factor V mutation.
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PMID:Use of the direct RNA amplification technique NASBA to detect factor V Leiden, a point mutation associated with APC resistance. 889 56

We have previously identified a group of blood donors with inherited deficiencies of either antithrombin (AT) or protein C who appear to have a relatively low thrombosis rate. In the 5 years that have elapsed since initial identification of these individuals, resistance to activated protein C (APC resistance), which is associated with the factor V Leiden gene mutation, has emerged as an important and highly prevalent inherited thrombophilic risk factor. We have followed 28 donors/relatives with deficiency of AT (median age 48 years, range 16-77) and 23 with deficiency of protein C (median age 44 years, range 15-79) over a period of 5 years. During the study period only one individual, who was previously symptomatic, has suffered a thrombotic event which occurred spontaneously whilst on warfarin. We have now excluded coinheritance of APC resistance due to the factor V Leiden mutation in our cohort. Our findings demonstrate that individuals with single inherited thrombophilic defects are not uncommon and are frequently asymptomatic. The absence of the factor V Leiden mutation may in part explain the low thrombosis rate observed, and lends support to the hypothesis that multiple thrombophilic defects may be necessary for the development of thrombosis.
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PMID:Low thrombosis rate seen in blood donors and their relatives with inherited deficiencies of antithrombin and protein C: correlation with type of defect, family history, and absence of the factor V Leiden mutation. 895 91

The diagnostic strategies and clinical characteristics of thrombophilia associated with heterozygous or homozygous factor V Leiden mutation have been determined according to the literature and to a personal study in 51 families. Factor V mutation was present in the 51 propositi and in 84 out of 125 family members (81 heterozygous, 3 homozygous). Venous thrombosis was observed in all the propositi, in 17 of the 84 family members with the mutation and in 6 of the 41 with a normal APC resistance test and no mutation. An associated protein C or protein S deficiency was present in 5 families (10%). The most frequent clinical manifestations were superficial or deep vein thrombosis and/or pulmonary embolism, but also thrombosis at an unusual site (cerebral, mesenteric or central retinal vein). A causal relationship is frequently difficult to demonstrate. A precipitating factor was observed in 84% of cases and a recurrent thrombotic episode occurred in 50% of propositi. The risk of thrombosis associated with pregnancy was high in the post-partum period, especially in homozygous women. In the 28 homozygous subjects, markers of coagulation activation were frequently elevated in untreated patients. Finally, the efficacy of anticoagulant treatment is suggested but the long period often observed between treatment interruption and a recurrence does not militate in favour of long term treatment.
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PMID:Diagnosis and clinical characteristics of inherited activated protein C resistance. 897 37

The discovery of APC resistance and of the factor V Leiden mutation brought a break-through in thrombosis research and has greatly improved our understanding of the pathogenesis of venous thrombosis. In particular, it became obvious that thrombotic disease is the result of multiple factors. However, many clinically relevant questions still remain unanswered: for instance, the individual risk of thrombosis for a gene carrier is difficult to assess, since only some of the factors which may finally lead to thrombosis are presently recognized as such. The functional tests which are in common use today have a number of drawbacks and will soon be replaced by improved methods.
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PMID:[Activated protein C resistance--an evaluation of current status]. 901 44


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