Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden

2008 ◽  
Vol 99 (01) ◽  
pp. 223-228 ◽  
Author(s):  
Jèrôme Duchemin ◽  
Christophe Leroyer ◽  
Bènèdicte Delahousse ◽  
Jean François Abgrall ◽  
Dominique Mottier ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Thrombin Generation ◽  
Adjusted Odds Ratio ◽  
Factor V Leiden ◽  
Factor V ◽  
Oestrogen Therapy ◽  
Prothrombotic State ◽  
First Degree Relatives ◽  
Generation Test

SummaryThe thrombin generation test appears to be a highly sensitive and specific test in the detection of thrombophilia in patients with venous thromboembolism. We aimed to determine the accuracy of the thrombin generation test to detect factorV Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden. Sixty-two first-degree relatives of 21 index cases were tested for factor V Leiden, the G20210A prothrombin gene mutation and thrombin generation. Information about oestrogen therapy and previousVTE was also collected. The normalized Thrombomodulin sensitivity ratio (n-TMsr) was defined as the ratio of endogenous thrombin potential determined in the presence and absence of thrombomodulin which was normalized against the same ratio determined in normal control plasma. The mean n-TMsr was 1.37 (± 0.33) in the 45 relatives with one or more prothrombotic state (factor V Leiden, G20210A prothrombin mutation, oestrogen therapy or hormonal therapy) and 1.02 (± 0.34) in the 17 relatives without prothrombotic state (p = 0.001). The positive predictive value was 90.3 (95%CI, 73.1 – 97.4). In relatives with an abnormal n-TMsr, the adjusted odds ratio for having a prothrombotic state was 8.3 (95%CI, 1.9 – 36.9) and the adjusted odds ratio for having the factor V Leiden was 14.3 (95%CI, 2.9 – 71.2).An abnormal thrombin generation test appears highly predictive for having factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden.

Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism

2001 ◽  
Vol 86 (09) ◽  
pp. 809-816 ◽  
Author(s):  
Frits Rosendaal ◽  
Marco Cattaneo ◽  
Maurizio Margaglione ◽  
Valerio De Stefano ◽  
Tony Cumming ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Large Population ◽  
Factor V Leiden ◽  
Pooled Analysis ◽  
Factor V ◽  
Case Control Studies ◽  
Vein Thrombosis ◽  
G20210a Mutation ◽  
Factor Ii

SummaryFactor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-18.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

Effect of hemostatic risk factors on the individual probability of thrombosis during pregnancy and the puerperium

2003 ◽  
Vol 90 (07) ◽  
pp. 77-85 ◽  
Author(s):  
Andrea Gerhardt ◽  
Rainer Zotz ◽  
Rüdiger Scharf
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Factor V ◽  
G20210a Mutation ◽  
Individual Probability ◽  
History Of ◽  
Normal Women ◽  
The Individual ◽  
Von Willebrand

SummaryIn a retrospective study of 190 women with a first history of venous thromboembolism during pregnancy and the puerperium and 190 age-matched women with at least one prior pregnancy and no history of venous thromboembolism, the individual probability of thrombosis was determined. Assuming an overall risk of 1 in 1500 pregnancies, the probability of pregnancy-related thrombosis in carriers of homozygous factor V Leiden was 1 in 80 (odds ratio 20.6, p=0.005) and among carriers of combined heterozygous factor V Leiden and heterozygous G20210A mutation in the prothrombin gene 1 in 20 (odds ratio 88, p<0.001). The probability of thrombosis per pregnancy among women with elevated levels of factor VIII:C (>172 % activity) was 1 in 385 (odds ratio 4.5, p<0.001) and among those with increased levels of von Willebrand factor antigen (>190 %) 1 in 435 (odds ratio 4.0, p=0.002), independent of elevated factor VIII:C levels. The high prevalence of combined and homozygous defects of hemostatic components (21.6%) in patients as compared with normal women (0.86%) supports the concept that venous thromboembolism is a multicausal disorder.

Age May Modify the Relationship between Factor V Leiden Mutation - but Not G20210A Prothrombin Gene Variation - and Idiopathic Venous Thromboembolism: An Hospital-Based Case-Control Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4052-4052
Author(s):  
Gregoire Le Gal ◽  
Karine Lacut ◽  
Francis Couturaud ◽  
Emmanuel Oger ◽  
Dominique Mottier
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Case Control Study ◽  
Factor V Leiden ◽  
Case Control ◽  
Factor V ◽  
Gene Variation ◽  
Prothrombin Gene ◽  
Control Study

Abstract Introduction: Factor V Leiden is the most common inherited risk factor for venous thromboembolism (VTE). A four- to sevenfold increased risk of VTE for the heterozygous state has been reported by numerous epidemiological studies but most of them did not include patients over 70 years. Surprisingly, we found in a previous study no association between Factor V Leiden and VTE in patients over 70 years. Methods Therefore we conducted a large hospital-based matched case-control study to test the hypothesis of an interaction between age and the factor V mutation, as well as G20210A prothrombin gene variation. Results: We analysed 392 patients experiencing VTE not related to a major acquired risk factor and their matched controls. Factor V Leiden was not associated with VTE in patients aged 80 years and over: odds ratio 0.8 (95%CI 0.2-3.4). There was a significant interaction between age and the mutation for VTE risk (p=0.03). Conversely, the association between the G20210A variant and VTE was consistent across age-groups: odds ratio 2.8 (95%CI 1.4–5.8). In conclusion, age may modify the relation between factor V Leiden and VTE. The prevalence of the factor V mutation decreased with increasing age among patients with VTE but not among controls.

Prediction of Recurrent Venous Thromboembolism by Endogenous Thrombin Potential and D-Dimer

2008 ◽  
Vol 54 (12) ◽  
pp. 2042-2048 ◽  
Author(s):  
Sabine Eichinger ◽  
Gregor Hron ◽  
Marietta Kollars ◽  
Paul A Kyrle
Keyword(s):  
Venous Thromboembolism ◽  
Thrombin Generation ◽  
Factor V Leiden ◽  
Study Endpoint ◽  
Factor V ◽  
Risk Of Recurrence ◽  
Endogenous Thrombin Potential ◽  
Increased Risk ◽  
Recurrent Venous Thromboembolism ◽  
D Dimer

Abstract Background: Increased thrombin generation is associated with an increased risk of recurrent venous thromboembolism. We investigated the relation between endogenous thrombin potential (ETP) and risk of recurrent venous thromboembolism and evaluated whether prediction of recurrence can be improved by a combined analysis of ETP and D-dimer. Methods: We followed 861 patients with first spontaneous venous thromboembolism and determined ETP and D-dimer after discontinuation of anticoagulation. Patients with natural inhibitor deficiency, lupus anticoagulant, or cancer were excluded. The study endpoint was symptomatic recurrent venous thromboembolism. Results: One hundred thirty patients (15.1%) had recurrence. High ETP (≥100%) conferred a 1.6-fold increased risk of recurrence (95% CI 1.1–2.3) after adjustment for age, sex, factor V Leiden, factor II G20210A, and duration of anticoagulation. After adjustment for D-dimer, risk of recurrence remained significantly higher among patients with high ETP [hazard ratio 1.6 (95% CI 1.01–2.4)]. After adjustment for ETP, high D-dimer (≥0.5 mg/L) conferred a 1.8-fold (95% CI 1.1–2.8) increased risk of recurrence. Compared with patients with low ETP and low D-dimer, risk of recurrence was 2.8-fold (95% CI 1.5–5.3) higher among patients with both high ETP and high D-dimer after adjustment for potential confounders. Conclusions: ETP and D-dimer are independent predictors of recurrent venous thromboembolism. Assessing risk of recurrence can be optimized by combining these indicators of thrombin generation.

Prevalence of 20210 A Allele of the Prothrombin Gene in Venous Thromboembolism Patients

1998 ◽  
Vol 80 (07) ◽  
pp. 49-51 ◽  
Author(s):  
Bernard Mercier ◽  
Emmanuel Oger ◽  
Eric Chenu ◽  
Jean-François Abgrall ◽  
Claude Férec ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Clinical Suspicion ◽  
Control Group ◽  
Factor V ◽  
Factor V Gene ◽  
Prothrombin Gene ◽  
Allele Variation

SummaryBackground. The 20210 A allele variation in the 3’ -untranslated region of the prothrombin gene was recently identified as a risk factor as regards deep venous thrombosis. Aim. To assess the frequency of the variation in unselected patients with a proven venous thromboembolism (VTE). Methods. The presence of the prothrombin variation was determined in all consecutive patients referred from July 1994 to August 1997 for a clinical suspicion of VTE, and in whom the diagnosis was confirmed. A control group consisted of bone marrow volunteer donors. Results. Of the 366 patients included, 17 (4.6%) were carriers of the 20210 A allele (95% CI, 2.4% to 6.7%). The mutation was present in 1.0% of the 400 controls. Odds ratio for having VTE in the presence of the 20210 A allele was 4.8 (95% CI, 1.5 to 19.8). Forty-six (12.5%) patients had the mutation of the factor V gene and five (1.4%) patients shared both mutations. After excluding the carriers of the factor V mutation, odds ratio for having VTE in the presence of the 20210 A allele was 3.7 (95% CI, 1.1 to 13.6). Mean age at admission as well as mean age of the first VTE episode were both significantly higher in patients free from the two mutations studied, as compared to carriers of the 20210 A allele (p = 0.04 and 0.01, respectively). Conclusion. Our findings in a large series of patients (1) confirm the 20210 A allele prothrombin gene as a risk factor for VTE. (2) suggest that its association with the factor V Leiden is not uncommon.

Incidence of venous thromboembolism in first-degree relatives of patients with venous thromboembolism who have factor V Leiden

2006 ◽  
Vol 96 (12) ◽  
pp. 744-749 ◽  
Author(s):  
Clive Kearon ◽  
Christophe Leroyer ◽  
Bernard Mercier ◽  
Jean Abgrall ◽  
Grégoire Le Gal ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Annual Incidence ◽  
Factor V ◽  
Genetic Abnormality ◽  
First Degree Relatives ◽  
Threefold Increase ◽  
Increased Risk ◽  
Routine Prophylaxis ◽  
The Difference

SummaryThe factor V Leiden (FVL) mutation, a genetic abnormality with an autosomal mode of inheritance, is associated with an increased risk of venous thromboembolism (VTE). We aimed to determine the annual incidence of VTE in first-degree relatives of patients with VTE and FVL and to identify factors in patients and the relatives that influence this incidence. In this retrospective and prospective cohort study, the incidence of objectively diagnosed first episodes of VTE was assessed in 553 first-degree relatives of 161 patients with acute VTE and FVL. The annual incidence of VTE was 0.43% (95% CI, 0.3 to 0.56) with FVL and 0.17 % (95% CI, 0.07 to 0.27) without FVL (relative risk of 2.5, 95% CI, 1.3 to 4.7). A majority (70%) of episodes of VTE were provoked, and this proportion was similar with and without FVL. A larger proportion of VTE was provoked in women (83%) that in men (33%), with the difference accounted for by pregnancy and use of oral contraceptives. The proportion of pregnancies complicated by VTE was 3.9% (95% CI, 2.0–5.8) with FVL and 1.4% (95% CI, 0.04–2.7) without FVL. FVL is associated with a two-to threefold increase in VTE in first-degree relatives of patients with VTE. No subgroup of relatives was identified who require more than routine prophylaxis because of a particularly high risk of VTE.

Factor V Leiden and Prothrombin Gene G20210A Mutation in Children with Venous Thromboembolism

2002 ◽  
Vol 87 (06) ◽  
pp. 972-977 ◽  
Author(s):  
Mirta Hepner ◽  
Gabriela Sciuccati ◽  
Graciela Pieroni ◽  
Aurora Feliú-Torres ◽  
Claudia Mardaraz ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Factor V Leiden ◽  
Paediatric Population ◽  
Control Group ◽  
Factor V ◽  
G20210a Mutation ◽  
Prothrombin Gene ◽  
Haematological Analysis

SummaryTo determine whether factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) are risk factors for venous thromboembolism (VTE) in Argentinean children. One hundred and thirty consecutive children with VTE were prospectively assisted at a single centre. Blood samples were available from 110 of them for detailed haematological analysis. The prevalence of both mutations was compared with a control group. The odds ratio for VTE was significantly increased in patients with FVL (OR 3.64; 95% CI: 1.14-11.6, p <0.029) whereas odds ratio for VTE was not significantly increased in patients with PT20210A (OR 1.06; 95% CI: 0.24-4.73, p = 0.938). Combined disorders were found in 5 of the 10 children with the aforementioned mutations. In 21 children (19%) without these mutations other inherited and acquired disorders were detected. Our data show that FVL is a risk factor for VTE whereas PT20210A does not seem to be a risk factor in our paediatric population.

The −33T → C Polymorphism in Intron 7 of the TFPI Gene Influences the Risk of Venous Thromboembolism, Independently of the Factor V Leiden and Prothrombin Mutations

2002 ◽  
Vol 88 (08) ◽  
pp. 195-199 ◽  
Author(s):  
Delphine Borgel ◽  
Frédéric Fumeron ◽  
Didier Moatti ◽  
Martine Alhenc-Gelas ◽  
Bernard Grandchamp ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Gene Polymorphisms ◽  
Protective Factor ◽  
Thrombotic Event ◽  
Factor V Leiden ◽  
Oral Contraception ◽  
Factor V ◽  
Study Population ◽  
Prothrombin Gene

SummaryWe have previously identified, in intron 7 of the TFPI gene, a T to C single-base polymorphism (−33T→C) which is strongly associated with total circulating TFPI antigen levels. Here we examined the influence of this polymorphism on the risk of venous thromboembolism. The polymorphism was identified in the PATHROS study population (330 cases with venous thromboembolism and 826 controls). The CC genotype was found in 6.4% of cases and 10.2% of controls (age-adjusted odds ratio 0.6; 95% CI 0.3–0.9; p = 0.03). This protective effect persisted after adjustment for oral contraception and the factor V Leiden and prothrombin gene polymorphisms. In 171 controls and 49 cases in whom blood was taken at least three months after the thrombotic event, the CC genotype was associated with significantly higher total TFPI levels than the TT genotype. These results suggest that the CC genotype of the TFPI intron 7 polymorphism is an independent protective factor for venous thromboembolism, an effect probably mediated by increased TFPI levels.

Sign in / Sign up

Export Citation Format

Share Document