A Case Control Study of Deep Venous Thrombosis in Relation to Factor V G1691A (Leiden) and A4070G (HR2 Haplotype) Polymorphisms.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4095-4095
Author(s):  
Wassim Y. Almawi ◽  
Lobna Borgi-Bouaziz ◽  
Hezard Nathalie ◽  
Nguyen Philipe ◽  
Mahjoub Touhami
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Activated Protein C ◽  
Significant Risk ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Significant Risk Factor ◽  
Factor V ◽  
Haplotype Allele ◽  
Fv Leiden

Abstract Activated protein C resistance (APCR) is a significant risk factor for venous thromboembolism (VTE), and the factor V (FV) gene mutations G1691A (FV-Leiden) account for the majority of inherited APCR cases. An additional FV gene mutation, the A4074G (FV-HR2), was recently reported to induce a risk of VTE by some but not all groups. The aim of this study was to determine the prevalence of single and combined SNPs in 126 patients with documented deep venous thrombosis (DVT), and 197 control Tunisian subjects. The frequencies of FV-Leiden A allele (p <0.001; OR = 5.031), and HR2 G allele (p = 0.014; OR = 2.463) were significantly higher among DVT patients. Genotype differences were found between FV-Leiden G/A (p <0.001; OR = 3.936) and A/A (p = 0.013; OR = 11.529), but not HR2 A/G genotypes (p = 0.862; OR = 1.166), between patients and controls. While no linkage disequilibrium was noted between the FV 1691A and 4070G or A alleles, higher prevalence of the 1691G/4070G (p = 0.002; OR = 5.189) and the 1691A/4070A (p = 0.007; OR = 3.670) were noted among DVT patients than in control subjects. Collectively, this indicates that FV-Leiden, and to a lower extent HR2 haplotype, are important independent risk factors for DVT, and that their coinheritance does not increase significantly the DVT risk imparted by either. Factor V-Leiden and HR2 Haplotype Allele and Genotype Analysis Cases Controls P OR Factor V-Leiden G 0.8492 0.9670 0.004 0.087 A 0.1508 0.0609 <0.001 5.031 G/G 0.754 0.939 <0.001 0.199 G/A 0.190 0.056 <0.001 3.936 A/A 0.056 0.005 0.013 11.529 HR2 Haplotype A 0.8913 0.9492 1.000 0.352 G 0.1087 0.0508 0.014 2.463 A/A 0.855 0.873 0.862 0.858 A/G 0.145 0.127 0.862 1.166 G/G 0.000 0.000

Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation

2006 ◽  
Vol 95 (04) ◽  
pp. 728-734 ◽  
Author(s):  
Felipe Guerrero ◽  
Catherine Arnaud ◽  
Francoise Nguyen ◽  
Bernard Boneu ◽  
Pierre Sié
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Factor V Leiden Mutation ◽  
Risk Increase ◽  
Increased Risk

SummaryActivated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC).As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factorV depleted plasma pre-dilution (test B) and a direct factorX activation-based assay with the same pre-dilution (test C).We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95%CI 3.23–12.63; test B OR=2.72; 95%CI 1.50–4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR=3.22; 95%CI 1.47–7.08; test B OR=3.10; 95%CI 1.54–6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.

scholarly journals Homozygous Cystathionine β-Synthase Deficiency, Combined With Factor V Leiden or Thermolabile Methylenetetrahydrofolate Reductase in the Risk of Venous Thrombosis

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2015-2018 ◽  
Author(s):  
Leo A.J. Kluijtmans ◽  
Godfried H.J. Boers ◽  
Bert Verbruggen ◽  
Frans J.M. Trijbels ◽  
Irena R.O. Nováková ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Major Complication ◽  
Significant Risk Factor ◽  
Mthfr Gene ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Thrombotic Complications

Abstract Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine β-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C→T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.

scholarly journals Factor V Leiden, FII G20210A, MTHFR C677T mutations as risk factors for venous thrombosis during pregnancy and puerperium

2005 ◽  
Vol 62 (3) ◽  
pp. 201-205 ◽  
Author(s):  
Valentina Djordjevic ◽  
Ljiljana Rakicevic ◽  
Milos Spasic ◽  
Predrag Miljic ◽  
Danijela Mikovic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Factor V Leiden ◽  
Mthfr C677t ◽  
First Episode ◽  
Factor V ◽  
G20210a Mutation ◽  
Fv Leiden ◽  
Heterozygous Carriers

Background. Venous thrombosis is the most common cause of obstetric morbidity and mortality during pregnancy and puerperium. The incidence of pregnancy associated venous thrombosis varies from 1 in 1000 to 1 in 2000 deliveries. Factor V G1691A (FV Leiden), FII G20210A and MTHFR C677T mutations are the most common genetic risk factors for thromboembolism. The aim of this study was to establish the presence of these risk factors in a group of women with an episode of deep venous thrombosis during pregnancy or puerperium. Methods. The study was carried in a group of 45 women with the first episode of deep venous thrombosis during pregnancy or puerperium. The patients with antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, and autoimmune and malignant diseases were excluded from the study. FV Leiden, FII G20210A, and MTHFR C677T mutations were detected by polymerase chain reaction, followed by digestion with specific restriction enzymes. Results. Twenty heterozygous carriers of the FV Leiden mutation and one homozygous carrier were detected, which represents the frequencies of 44.4% and 2.2%, respectively. For the FII G20210A mutation, six heterozygous carriers were identified, giving the frequency of 13.3%. The MTHFR C677T mutation was observed in 31 patients (22 heterozygous and 9 homozygous carriers) which represents the frequencies of 48.9% and 20%, respectively. Conclusion. Our study suggested that the obligatory testing for FV Leiden and FII G20210A mutations was strongly recommended in women with history of venous thrombosis during pregnancy and puerperium. We found a slight effect of MTHFR 677T allele, but it should be considered in association with other risk factors.

scholarly journals Homozygous Cystathionine β-Synthase Deficiency, Combined With Factor V Leiden or Thermolabile Methylenetetrahydrofolate Reductase in the Risk of Venous Thrombosis

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2015-2018
Author(s):  
Leo A.J. Kluijtmans ◽  
Godfried H.J. Boers ◽  
Bert Verbruggen ◽  
Frans J.M. Trijbels ◽  
Irena R.O. Nováková ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Significant Risk ◽  
Factor V Leiden ◽  
Major Complication ◽  
Significant Risk Factor ◽  
Mthfr Gene ◽  
Factor V ◽  
Thromboembolic Complications ◽  
Thrombotic Complications

Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine β-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C→T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C→T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.

scholarly journals FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control Study

2011 ◽  
Vol 30 (1) ◽  
pp. 51-54
Author(s):  
Iva Salatić ◽  
Katarina Kiralj ◽  
Gorana Mitić ◽  
Igor Veselinović ◽  
Dušan Vapa
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Case Control Study ◽  
Factor V Leiden ◽  
Case Control ◽  
Factor V ◽  
Increased Risk ◽  
Fv Leiden ◽  
Heterozygous Carriers ◽  
Control Study

FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control StudyBetween September 2007 and February 2010, the occurrence of symptomatic deep venous thrombosis (DVT) was investigated in a cohort of 79 consecutive patients. A case-control study inclu ded 71 healthy controls matched with cases for sex and age. The prevalence of factor V G1691A mutation genotype was analyzed. Eighteen cases (22.79%; 95% confidence interval (CI) 13.53% to 32.03%) and four controls (5.63%; 95% CI 0.27% to 10.99%) were heterozygous carriers of FV Leiden (p= 0.025). The odds ratio for DVT was 4.94 (95% CI 1.58 to 15.42) and the relative risk 4.04 (95% CI 1.44-11.38) compared with FV 1691G carriers. Four cases were homozygous carriers of FV Leiden, giving a prevalence of 5.06% (95% CI 0.23 to 9.89%) and no controls, therefore OR and RR calculation was based on the prevalence of homozygotes in the general Caucasian population. The OR for DVT was 47.28 (95% CI 0.04 - 52167.3) and the RR 45.57 (95% CI 0.04 to 49540.77; p=0.025) compared with FV 1691 G carriers. Our study confirms that factor V Leiden carriers in Vojvodina, as in similar studies previously carried out in other populations, have an increased risk of developing DVT. The evaluated risk of DVT in heterozygous carriers of the mutation is four- to five-fold higher, whereas for homozygous carriers it is 45- to 48-fold higher than in non-carriers. These results confirm that patients with DVT and their relatives should undergo screening for FV Leiden mutation.

Resistance to Activated Protein C and Factor V Leiden as Risk Factors for Venous Thrombosis

1995 ◽  
Vol 74 (01) ◽  
pp. 449-453 ◽  
Author(s):  
Rogier M Bertina ◽  
Pieter H Reitsma ◽  
Frits R Rosendaal ◽  
Jan P Vandenbroucke
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V

Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

1997 ◽  
Vol 77 (05) ◽  
pp. 0822-0824 ◽  
Author(s):  
Elvira Grandone ◽  
Maurizio Margaglione ◽  
Donatella Colaizzo ◽  
Marina d'Addedda ◽  
Giuseppe Cappucci ◽  
...  
Keyword(s):  
Protein C ◽  
Strong Association ◽  
Activated Protein C ◽  
Fetal Loss ◽  
Factor V Leiden ◽  
Factor V ◽  
Significant Difference ◽  
History Of ◽  
Fv Leiden ◽  
Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

Combined Factor V Leiden (R506Q) and prothrombin G20210A genotyping in young patients presenting with deep venous thrombosis

2006 ◽  
Vol 21 (1) ◽  
pp. 24-27 ◽  
Author(s):  
A Mansilha ◽  
F Araújo ◽  
M Severo ◽  
S M Sampaio ◽  
T Toledo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Young People ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Young Patients ◽  
Factor V Leiden ◽  
First Episode ◽  
Control Group ◽  
Factor V ◽  
Factor V Leiden Mutation

Objective: To evaluate the association between the Factor V Leiden (FV R506Q) and prothrombin gene (FII G20210A) mutations and deep venous thrombosis (DVT) in young people. Methods: Blood samples were drawn from 199 subjects: 100 healthy controls and 99 unselected patients, with an objectively documented first episode of DVT under 40 years old. DNA analysis was performed using the polymerase chain reaction. Results: The mean age in the patient cohort was 27 years (range 16–40) and 68 (68.7%) were women. Patient prevalences were 20.6% and 10.1% for FV R506Q and FII G20210A, respectively. In the control group, carrier frequencies were 2% and 5%, respectively. We found an increased overall relative risk of DVT with statistical significance for FV R506Q carriers (OR: 12.8; 95% CI: 2.9–56.7; P < 0.001), but not for FII G20210A mutation (OR: 2.1; 95% CI: 0.7–6.5; P = 0.19). Conclusions: Our results suggest a possible increase in DVT risk for the young G20210A allele carriers, which can be more expressed in the presence of a circumstantial risk factor. There is extremely strong evidence that the Factor V Leiden mutation is an important risk factor in the development of a first episode of DVT in young people.

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