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 exhi bit a response in functional APC-resistance tests similar to that of carrie rs of factor VLeiden are considered to be acquired APC resistant. This phen omenon 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 functio nal 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 b etween non-OC users and OC users and between users of second and third gene ration OC, Since there was no correlation between APC-sensitivity determine d 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 o ther plasma components differentially modulate the response to APC in the a PTT- and ETP-based APC-resistance tests and that OC change the level of pla sma protein(s) that modulate the effect of APC on thrombin formation initia ted via the extrinsic coagulation pathway.