Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A point mutation in coagulation factor V which causes resistance to cleavage of factor Va by activated protein C (APC), was recently found to underlie thrombotic events. We examined 20 consecutive patients, under the age of 40, who suffered from idiopathic venous or arterial thrombosis. In 8 (40%) there was resistance to APC manifested by absence of the expected prolongation of activated partial thromboplastin time (aPTT). In 3, the addition of normal plasma corrected the anomaly in the patient's plasma, although the addition of factor V- deficient plasma caused no change. In a family of a 17-year-old boy with idiopathic deep venous thrombosis we found a mutation in factor V which was responsible for APC resistance. The patient and 4 family members showed a single G to A transition in position 1691 in their cDNA, resulting in substitution of arginine (506) for glutamine. The mutation in this area, which is the cleavage site for APC, is associated with thrombotic episodes and is frequently observed in patients with familial thrombophilia.
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PMID:[Resistance to activated protein C--a novel cause of thrombophilia]. 755 99

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.
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PMID:[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. 852 25

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20% to 30% of patients with a history of deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5 to 10 fold in heterozygotes, and 50- to 100- fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis or in the occurrence of myocardial infarction.
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PMID:[Activated protein C resistance: role in venous and arterial thrombosis]. 876 Jun 61

Activated protein C resistance is the most prevalent cause of thrombophilia: it is found in 20 to 30% of patients with a deep venous thrombosis history. Activated protein C resistance is due to an arginine 506 to glutamine mutation in factor V. This mutation prevents normal inactivation of activated factor V by activated protein C. The estimated increase in relative risk of venous thrombosis is 5- to 10-fold in heterozygotes, and 50- to 100-fold in homozygotes. Activated protein C resistance does not seem to play a role in arterial thrombosis and in the occurrence of myocardial infarction.
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PMID:Resistance to activated protein C: role in venous and arterial thrombosis. 895 64

Ultrasound is used as a primary diagnostic technique for the detection of deep venous thrombosis. The purpose of this study is to describe the development of a new thrombus-specific ultrasound contrast agent: The linear hexapeptide (lysine-glutamine-alanine-glycine-aspartate-valine) was synthesized and coupled to a lipid moiety. The targeted lipid was then incorporated into the lipid blend for the contrast agent Aerosomes (ImaRx, Tucson, AZ, USA). The lipid blend was used to entrap perfluorobutane microbubbles. The microbubbles were sized and studied in vitro for acoustic stability, binding to blood clot, and ultrasound enhancement in vitro of blood clot. The results showed the mean size of the specific ultrasound contrast agent (MRX-408) was about 2.0 microm. The microbubbles appeared as smooth spherical structures. Microscopy showed that the targeted bubbles bound to blood clot whereas control, nontargeted bubbles did not bind to blood clot. In vitro acoustic study showed similar stability of the microbubbles compared with control microbubbles. The targeted microbubbles enhanced blood clot in vitro whereas nontargeted microbubbles did not enhance clot. Thus this promising new thrombus-specific ultrasound contrast agent could potentially improve detection of thrombosis by ultrasound and might be useful for distinguishing between new and old thrombosis. In vivo studies are in progress.
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PMID:In vitro studies of a new thrombus-specific ultrasound contrast agent. 966 29

HyBeacon probes are single-stranded oligonucleotides with one or more internal base(s) labeled with a fluorescent dye. When a probe forms a duplex with its target sequence, the level of fluorescence emission increases considerably. HyBeacons have been developed as new tools for rapid sequence detection and discrimination and have been employed in a wide variety of applications including infectious diagnostics and analysis of human polymorphisms. Single-labeled (FVG1) and dual-labeled (FVG11) probes were designed to analyze the factor V Leiden (R506Q) polymorphism which causes an increased risk of deep vein thrombosis and pulmonary embolism. Detection and identification of factor V alleles is performed by melting curve analysis and determination of probe melting temperature (T(m)). HyBeacon hybridization to the glutamine allele (Q) causes the formation of mismatched DNA duplexes that are detected through decreases in T(m). HyBeacon probes are included in homogeneous PCR assays to genotype samples with respect to the factor V polymorphism within 20 min, using purified DNAs and unpurified saliva/blood samples. This paper describes the preparation of homogeneous PCR assays, LightCycler target amplification, and subsequent melting curve analysis. This chapter also describes the use of homologous oligonucleotides and melting curve analysis as a method for probe evaluation.
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PMID:HyBeacon probes for rapid DNA sequence detection and allele discrimination. 1869 66

Activated protein C resistance (APCR) describes a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. Protein C is a natural anticoagulant that is synthesized in the liver and is activated to APC via proteolysis. APC then degrades Factors Va and VIIIa. APCR describes the reduced inability of APC to cleave Factors Va and VIIIa, which therefore promotes increased thrombin generation and potentially leads to a prothrombotic state. APCR may be hereditary or acquired. The most common hereditary defect is due to mutations in Factor V, predominantly the Factor V Leiden [FVL] mutation-a G1691A missense mutation at Arginine 506 that results in its replacement by a glutamine [R506Q] and the abolition of an APC inactivation cleavage site in Factor Va. Laboratory testing for APCR may be undertaken by a variety of methods, but this chapter describes an automated procedure using a commercial Russell Viper Venom-based clotting assay, and using CS-5100 and STA-R analyzers.
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PMID:Laboratory Testing for Activated Protein C Resistance (APCR). 2880 24