Combined Effect of Factor V Leiden and Prothrombin 20210A on the Risk of Venous Thromboembolism - Pooled Analysis of 8 Case-control Studies Including 2310 Cases and 3204 Controls
Joseph Emmerich, Frits R. Rosendaal, Marco Cattaneo, Maurizio Margaglione, Valerio De Stefano, Tony Cumming, Valder Arruda, Andreas Hillarp, Jean-Luc Reny, for the study group for pooled-analysis in venous thromboembolism*
Paris: J. Emmerich, J. L. Reny, E. Arnaud, M. Alhenc-Gelas [Hôpital Européen Georges Pompidou, Service de Médecine Vasculaire (Centre Claude Bernard) et Laboratoire d’Hémostase, Paris, France]; Leiden: F. R. Rosendaal, T. Koster, J. P. Vandenbroucke, R.
Factor 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