Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis.
We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis.
For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age-and sex-matched controls.
All carriers of the factor V Leiden mutation were excluded.
A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis : the lower the normalized APC sensitivity ratio, the higher the associated risk.
The risk for the lowest quartile of normalized APC-SR (<0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR>1.05) was greater than fourfold increased (OR=4.4 ; 95% confidence interval, 2.9 to 6.6).
We adjusted for VIII : C levels, which appeared to affect our APC resistance test.
The adjusted (age, sex, FVIII : C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2).
So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor.
Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.
Mots-clés Pascal : Thrombose, Veine, Facteur risque, Epidémiologie, Résistance, Protein C (activated), Serine endopeptidases, Peptidases, Hydrolases, Enzyme, Anticoagulant, Endogène, Etude cas témoin, Pays Bas, Europe, Homme, Appareil circulatoire pathologie, Vaisseau sanguin pathologie, Veine pathologie, Hémopathie, Coagulopathie, Maladie héréditaire
Mots-clés Pascal anglais : Thrombosis, Vein, Risk factor, Epidemiology, Resistance, Protein C (activated), Serine endopeptidases, Peptidases, Hydrolases, Enzyme, Anticoagulant, Endogenous, Case control study, Netherlands, Europe, Human, Cardiovascular disease, Vascular disease, Venous disease, Hemopathy, Coagulopathy, Genetic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0133952
Code Inist : 002B12B03. Création : 16/11/1999.