Summary

The factor V Leiden mutation (FVL), associated with reducedsensitivity to activated Protein C (APC), is a risk factor forvenous thromboembolism (VTE) and displays a strong interactionwith oral contraceptives (OC). The aim of this study wasto evaluate the risk of VTE in OC users with reduced APC sensitivityunrelated to the FVL. APC sensitivity was measured byan original aPTT-based test (without sample pre-dilution in factorV-deficient plasma) in 195 women who suffered from VTE inreproductive age and in 487 healthy women with results beingexpressed as normalized ratio. Subjects with currently knownclinically relevant thrombophilic alterations were excluded.APC normalized ratios were stratified into quartiles. Theadjusted ORs of subjects in the lower quartile (≤0.90) was 2.46 (95%CI: 1.02-5.95). Of the 195 patients, 89 had suffered VTEduring OC. The 181 healthy women who had used OC for atleast 6 months in the two year period before presentation butwho had stopped OC at least 3 months before blood samplingwere considered OC users. The risk of VTE in subjects usingOC with APC normalized ratio in the lower quartile wasincreased 4.9-fold (95% CI: 1.92-12.6). In conclusion, our resultsshowed that altered APC resistance in women not carrying theFVL significantly increased the VTE risk, albeit to a lesser extentthan in women also carrying the FVL. Our data also showedthat OC use in women with altered APC resistance furtherincreased the risk of VTE in a way that exceeded the additiveexpectation.