Acquired activated protein C resistance in postmenopausal women is dependent on factor VIII : c levels

Activated protein C (APC) resistance is an established risk factor for veno us thromboembolism. In 5% to 10% of patients with venous thromboembolism, t he APC resistance phenotype is observed in the absence of factor V Leiden m utation. Moreover some physiologic and pathologic conditions are associated with an "acquired" APC resistance, not caused by the Leiden mutation, such as inflammatory diseases pregnancy, or oral contraceptive therapy Several studies have demonstrated the effect of menopause on the hemostatic system, but no data are available about APC resistance. We found a high prevalence of APC resistance in postmenopausal women, not associated with factor V Le iden mutation. The mechanism that underlies this acquired APC resistance ma y be related to the higher levels of factor VIII; which showed a strong inv erse correlation with APC resistance whereas no correlation was found betwe en the normalized APC ratio, factor V levels, and protein S values. Higher levels of factor VIII correlated with a marker of coagulation activation su ch as prothrombin fragments I plus 2. Therefore, to identify women receivin g hormone replacement therapy who have a greater risk for deep venous throm bosis, the APC resistance coagulation test should be used instead of the ge netic study.