Acquired APC resistance and oral contraceptives: differences between two functional tests

Resistance to activated protein C (APC) is often associated with a mutation in factor V (factor V-Leiden) Individuals without factor V-Leiden who exhibit a response in functional APC-resistance tests similar to that of carriers of factor VLeiden are considered to be acquired APC resistant. This phenomenon is particularly observed in women using oral contraceptives (OC). In the present study we compared the response to APC in plasma from normal individuals, carriers of factor V-Leiden and women who use OC using functional tests that either quantify the effect of APC on the endogenous thrombin potential (ETP) or on the activated partial thromboplastin time (aPTT). Both tests discriminated equally well between individuals with and without factor V-Leiden who were not using OC. In contrast to the aPTT-based test, the ETP-based assay yielded significant differences in sensitivity to APC between non-OC users and OC users and between users of second and third generation OC, Since there was no correlation between APC-sensitivity determined with both assays in non-carriers of factor V-Leiden and in women who use OC and a poor correlation in carriers of factor V-Leiden, We propose that other plasma components differentially modulate the response to APC in the aPTT- and ETP-based APC-resistance tests and that OC change the level of plasma protein(s) that modulate the effect of APC on thrombin formation initiated via the extrinsic coagulation pathway.