PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “FACTOR V”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Identification of the V factor needed for synthesis of the iron-molybdenum cofactor of nitrogenase as homocitrate.

Nitrogenase catalyses the ATP-dependent reduction of N2 to NH3, and is composed of two proteins, dinitrogenase (MoFe protein or component I) and dinitrogenase reductase (Fe protein or component II). Dinitrogenase contains a unique prosthetic group (iron-molybdenum cofactor, FeMoco) comprised of Fe, Mo and S, which has been proposed as the site of N2 reduction. Biochemical and genetic studies of Nif- (nitrogen fixation) mutants of Klebsiella pneumoniae which are defective in nitrogen fixation, have shown that the nifB, nifQ, nifN, nifE and nifV genes are required for the biosynthesis of FeMo-co. Recently, a system for in vitro synthesis of FeMoco was described. The assay requires at least the nifB, nifN and nifE gene products, and a low-molecular-weight factor (V factor) produced in the presence of the nifV gene product. We have used this system to study FeMoco biosynthesis. We report here the isolation of V factor and identify it as homocitric acid ([R]2-hydroxy-1,2,4-butanetricarboxylic acid).

Ferredoxins↗
PubMed2004

Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay.

A new prothrombin-based activated protein C resistance (APC-R) test is described. In this method, the patient sample is prediluted in a plasma depleted of factor V (FV). A reagent containing APC and a specific activator of FV is added. After an incubation period, clotting is initiated by the addition of the FV-dependent prothrombin activator Noscarin. We analyzed 703 samples from patients undergoing thrombophilia screening. By using a predefined cutoff ratio of 2.5, 100% sensitivity and specificity for the detection of a factor V Leiden (FVL) mutation was found. With a cutoff ratio of 1.2, a complete but narrow distinction of FVL heterozygous (n = 192) and FVL homozygous samples (n = 27) was determined. No interference by the international normalized ratio, activated partial thromboplastin time (aPTT), protein S activity, fibrinogen and factor VIII (FVIII) levels, or lupus anticoagulant ratio was detected. The new prothrombin-based APC-R assay provides improved distinction of FV wild-type and FVL carriers compared with the aPTT-based method. By the use of an FV-dependent prothrombin activator, the assay is not influenced by FVIII concentration or lupus anticoagulants.

Blood Coagulation Tests↗
PubMed2000

Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria.

Mutations in the gene for prothrombin (F2 20210A) and factor V (F5 1691A, factor V Leiden) are established risk factors for deep venous thrombosis (DVT). Recently, a mutation in the gene for factor XIII (F13 100T) leading to a Valine-Leucine exchange at amino acid position 34 has been reported to be protective against DVT. To analyze the role of these mutations for DVT in Austria, we analyzed their prevalence in 154 patients with documented DVT and 308 sex- and age-matched control subjects. Allele frequencies of F2 20210A, F5 1691A, and F13 100T were 0.018, 0.039, and 0.274 among controls, and 0.045, 0.120, and 0.211 among patients, respectively. Odds ratios for DVT associated with F2 20210A, F5 1691A, and F13 100T alleles were 2.5 (95% CI: 1.1-5.7), 3.4 (95% CI: 1.9-5.8), and 0.7 (95% CI: 0.5-1.0). We conclude that F2 20210A, F5 1691A, and F13 100T are common mutations in the Austrian population. F2 20210A and F5 1691 increase the risk for DVT, whereas F13 100T is associated with a decreased risk for DVT. Routinely, analysis of these mutations may help to analyze the individual risk for DVT.

Adolescent↗
PubMed2004

Factor V Leiden: a disorder of factor V anticoagulant function.

PURPOSE OF REVIEW: Activated protein C (APC) resistance, which is often associated with the factor V R506Q (FV Leiden) mutation, is a common risk factor for venous thrombosis. Study of the mechanism of APC resistance has revealed that coagulation FV stimulates the APC-catalysed inactivation of FVIIIa, and that this anticoagulant function of FV is impaired in FV Leiden. The present review covers the discovery, the physiological significance and the structural requirements of the APC-cofactor activity of FV. RECENT FINDINGS: Recent in vitro and in vivo experiments indicate that the anticoagulant activity of FV is physiologically relevant and that FV plays a major role in the maintenance of the haemostatic balance. Quantitative and functional defects of the APC-cofactor activity of FV lead to increased thrombin generation and are associated with a prothrombotic state. Although the structural requirements for the expression of the APC-cofactor activity of FV are now beginning to be unravelled, the underlying molecular mechanism remains elusive. SUMMARY: The APC-cofactor activity of FV and its impairment in FV Leiden can explain the different thrombosis risks associated with heterozygosity, homozygosity and pseudo-homozygosity for FV Leiden. Elucidation of the molecular mechanism of the anticoagulant function of factor V may provide novel targets for the design of antithrombotic drugs.

Activated Protein C Resistance↗
PubMed2003

Coagulation factor V G allele and HR2 haplotype: factor V activity, activated protein C resistance and risk of venous thrombosis.

Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case-control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58-1.30; P = 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89; P = 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.

Activated Protein C Resistance↗
PubMed1999

Mechanisms that regulate the anticoagulant function of coagulation factor V.

Coagulation factor V is composed of domains A1-A2-B-A3-C1-C2 and is activated by thrombin through proteolytic cleavage at Arg 709, Arg 1018 and Arg 1545. Upon thrombin activation, the B-domain is released and the active factor Va is formed by the heavy (A1-A2) and light chains (A3-C1-C2). Factor Va functions as an essential cofactor to factor Xa in the conversion of prothrombin to thrombin during coagulation. Recently it was shown that coagulation factor V, apart from being a precursor form to the procoagulant factor Va, also has anticoagulant properties, as it functions as a cofactor to activated protein C (APC). APC is a member of the anticoagulant pathway and downregulates the coagulation process through proteolytic inactivation of factors VIII/VIIIa and factors V/Va. In a factor VIIIa degradation assay, the APC-mediated inactivation of factor VIIIa is potentiated by the synergistic cofactors protein S and factor V. Protein S alone has little cofactor activity, whereas in the presence of factor V it is dramatically enhanced. This study provides insights into the molecular mechanisms that regulate the anticoagulant activity of factor V. Thrombin cleavage of factor V occurs in a sequential order. The thrombin cleavage site Arg 1545 is kinetically less favored than the other two sites, and cleavage at this site is the last to occur during thrombin activation of factor V As a consequence of this, different activation intermediates exist that express different levels of procoagulant activity. The anticoagulant activities of these intermediates have now been studied. It was found that factor V could be cleaved by thrombin at both Arg 709 and Arg 1018 and still work fully as a cofactor to APC, whereas cleavage at Arg 1545 completely abolished the anticoagulant activity of factor V. This suggests that the APC cofactor function of factor V depends on the B-domain remaining attached to the A3 domain. This study further shows that APC converts coagulation factor V into a member of the anticoagulant pathway by cleaving factor V in the A2 domain at Arg 506. By cleavage of factor V, APC not only produces an anticoagulant cofactor, but at the same time eliminates the pool of procoagulant factor V, since APC cleaved factor V will have no future as a cofactor in the coagulation. The unique way by which APC and thrombin, through proteolytic cleavage, can convert factor V into either an anticoagulant or a procoagulant adds to the intriguing mechanisms that balance the procoagulant and anticoagulant forces.

Blood Coagulation↗
PubMed2002

Homozygous factor V splice site mutation associated with severe factor V deficiency.

We investigated a family whose proband has a severe bleeding disorder and factor V antigenic and functional levels of 8% and less than 1% of control values, respectively. Molecular analysis of the factor V gene revealed a novel homozygous mutation in the last nucleotide of exon 10. 1701G>T causes activation of a cryptic exonic splice site in exon 10, which encodes part of the factor V heavy chain (A2 domain). This leads to the deletion of 35 nucleotides and results in a frameshift with a premature stop codon at amino acid position 498. The G1701 and corresponding Gln509 are conserved in murine, bovine, and porcine factor V and in human factor VIII. Few factor V deficiency mutations have been identified as yet. Several are present in the heterozygous form in combination with factor V Leiden (Arg506Gln). This is the first reported homozygous splice site mutation in a patient with factor V deficiency.

Blood Transfusion↗