The association between extrinsic activated protein C resistance and venous thromboembolism in women.

Abstract Recently, discussions have focused on the question of whether acquired APC resistance (APCsr) is a clue to the observed association between risk of venous thromboembolism (VTE) and OC use especially with the so-called third-generation OCs. It seems plausible that abnormalities in an extrinsic-based APCsr reflect an increased risk of VTE in women, but this has not yet been properly studied. The objective of our study was to determine whether there was an association of extrinsic APC resistance with VTE risk in a case-control study. Sixty-seven women with confirmed VTE diagnosis were consecutively recruited in primary health care settings, interviewed and blood samples were taken at least 6 months after VTE. Cases were age-matched to 290 population controls. Extrinsic APC resistance was measured as normalized APC ratio (APCsr). The effect of APC on tissue factor-initiated thrombin generation was measured in plasma using α2-macroglobulin attached thrombin activity as an endpoint. The extrinsic APCsr was significantly associated with factor V Leiden (FVL) mutation, both in the cases and in the controls. Also, in the women using OC, significantly higher values of APCsr were observed, which confirms the results of other studies. We did not identify a significant association between the extrinsic APCsr and VTE in women not using OC who are non-carriers of factor V Leiden using different approaches: comparison of medians, analyses with unconditional logistic regression using various cut-points of the APCsr distribution, and the comparison between the highest and the lowest quartile of APCsr. With all attempts, the risk estimates were close to unity. In conclusion, we were not able to find evidence for any association of extrinsic APCsr with VTE in women who were not using OCs and non-carriers of FVL.