Factor V Leiden mutation and pregnancy-related venous thromboembolism: What is the exact risk?

SummaryThe magnitude of the association of factor V Leiden mutation with pregnancy-related venous thrombosis remains unclear. Our objective was to undertake a systematic review and a meta-analysis of the literature to estimate precisely the association of factor V Leiden mutation with the risk of first,or recurrent,pregnancy-related venous thromboembolism. Studies published before October 2005 were identified by Medline®. Using both fixed and random effect models, odds ratios (OR) with accompanying 95% confidential intervals (CI) were calculated for the factor V Leiden mutation and the clinical end-point (Yusuf-Peto adaptation of the Mantel-Haenszel, DerSimonian and Laird method).We identified 13 studies including 7 cohorts and 6 case control studies relating to factor V Leiden and pregnancy-related venous thrombosis.The results from the cohorts showe a pooled OR of 4.46 (95% CI,1.82–10.94;7,879 pooled women), with no evidence of statistical heterogeneity (p=0.36), for the risk of a first venous thromboembolism during pregnancy or the postpartum period associated with the factor V Leiden mutation.Case-control studies revealed a higher risk ( OR 8.6,95% CI, 5.85–12.63; 1,524 pooled women) with significant heterogeneity (p<0.005). Because of insufficient data, an analysis for the risk of recurrence could not be performed. Our findings emphasize the fact that limited data are available on this topic.This meta-analysis provides clinicians with an estimate of the average risk of a first thrombosis occurring during pregnancy in women carrying the factor V Leiden to assist the management of such women.

Download Full-text

The genetics of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th09-01-0013 ◽

2009 ◽

Vol 102 (08) ◽

pp. 360-370 ◽

Cited By ~ 124

Author(s):

Reya Gohil ◽

George Peck ◽

Pankaj Sharma

Keyword(s):

Venous Thromboembolism ◽

Meta Analysis ◽

Random Effect ◽

Case Control ◽

Disease Association ◽

Factor V ◽

Case Control Studies ◽

Factor V G1691a ◽

Meta Analyses ◽

Random Effect Models

SummaryWe conducted a systematic and comprehensive meta-analysis on all candidate genes to assess their genetic contribution to the aetiology of venous thromboembolism (VTE) (pulmonary embolism and deep venous thrombosis) in all ethnic groups. Electronic databases were searched until and including January 2008 for any candidate gene investigated in VTE. Odds ratios (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Our meta-analyses included ∼126,525 cases and 184,068 controls derived from 173 case-control studies, which included 21 genes (28 polymorphisms). Statistically significant associations with VTE were identified for factor V G1691A (OR 9.45; 95% CI 6.72–13.30, p<0.0001), factor V A4070G (OR 1.24; 95% CI

Download Full-text

The Incidence of Venous Thromboembolism in Family Members of Patients with Factor V Leiden Mutation and Venous Thrombosis

Annals of Internal Medicine ◽

10.7326/0003-4819-128-1-199801010-00003 ◽

1998 ◽

Vol 128 (1) ◽

pp. 15 ◽

Cited By ~ 129

Author(s):

Saskia Middeldorp

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Family Members ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation

Download Full-text

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1616136 ◽

2001 ◽

Vol 86 (09) ◽

pp. 809-816 ◽

Cited By ~ 193

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.

Download Full-text

Factor V Leiden mutation: the most commonly inherited risk factor for venous thromboembolism

Primary Care Update for OB/GYNS ◽

10.1016/s1068-607x(99)00014-1 ◽

1999 ◽

Vol 6 (5) ◽

pp. 141-146 ◽

Cited By ~ 1

Author(s):

Annette M Miles ◽

Manju Monga

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Inherited Risk

Download Full-text

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613052 ◽

2002 ◽

Vol 87 (04) ◽

pp. 580-585 ◽

Cited By ~ 59

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.

Download Full-text