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.

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.

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.

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.

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.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

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.

scholarly journals Heritable Thrombophilia in Venous Thromboembolism in Northern Pakistan: A Cross-Sectional Study

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Maria Khan ◽  
Chaudhry Altaf ◽  
Hamid Saeed Malik ◽  
Muhammad Abdul Naeem ◽  
Aamna Latif
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Factor V ◽  
Protein C Deficiency ◽  
Factor V Leiden Mutation ◽  
Inherited Thrombophilia ◽  
At Deficiency ◽  
Prothrombin Gene

Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects.

scholarly journals Evaluation of Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism for Inherited Thrombophilia Disorders

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5007-5007 ◽  
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Ravitharan Krishnadasan ◽  
Pavani Chalasani ◽  
Ivo Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Inherited Thrombophilia ◽  
Dvt Prophylaxis ◽  
Prothrombin Gene ◽  
Baseline Characteristics

Abstract Background Venous thromboembolism can be classified according to the presence of either environmental or genetic risk factors. Risk factors for thrombosis can include activated protein C resistance, and heritable including deficiencies of antithrombin, protein C or protein S. Factor V Leiden deficiency and prothrombin gene mutations are some of the more common thrombophilias, with a slight increased risk for venous thromboembolism (VTE). Current guidelines suggest the use of low-molecular weight heparins for secondary prophylaxis in patients with VTE. However, there is a lack of data on the use of Direct Oral Anticoagulant (DOACs) in patients with inherited thrombophilia. We evaluated our use of rivaroxaban in patients with thrombophilia disorders treated for secondary DVT prophylaxis. Method We performed a retrospective evaluation of patients in our institution with inherited thrombophilia with an active VTE diagnosis who received DOACs for secondary prophylaxis from November 2013 until April 2016. Data collected included patient demographics, inherited thrombophilia mutation, previous history of VTE, prior treatments, and efficacy and safety of anticoagulation with DOACs. Results We had 13 patients with inherited thrombophilia mutation and 4 patients diagnosed with concomitant cancer (non-Hodgkin lymphoma, melanoma, and 2 with breast cancer) (Table 1). Out of 13 patients 3 failed warfarin, and one failed fondaparinux prior to switching to a DOAC. Mutation with heterozygous Factor V Leiden deficiency was reported in 7 patients, while mutations with Protein C and/or S deficiency were found in 4 patients. One patient had both Factor V Leiden and Protein C deficiency mutations. The prothrombin gene mutation was identified in one patient. The median of length of therapy was 2 years with 8/13 still on rivaroxaban in April 2016. The shortest treatment duration was 41 days for a patient who failed rivaroxaban with a second clot and was switched to apixaban without subsequent treatment failure. Two patients experienced 4 non-major episodes of gastrointestinal bleeding, nose bleeding and dark stool. One patient developed rash with noted bruising during their rivaroxaban therapy. Conclusion: This is the first report on outcomes for secondary DVT prophylaxis with DOACs in patients with underlying thrombophilia mutations. Safety and efficacy of DOACs for secondary VTE prophylaxis yielded favorable results; however, future prospective studies in the setting of thrombophilia are warranted. Table 1 Summary of baseline characteristics and outcomes. Table 1. Summary of baseline characteristics and outcomes. Disclosures McBride: Sanofi: Research Funding.

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