APC resistance and third-generation oral contraceptives: Acquired resistance to activated protein C, oral contraceptives and the risk of thromboembolic disease

Abstract

Using a newly-developed technique, a severe acquired plasma resistance to activated protein C has been described in women using third-generation (rather than second-generation) oral contraceptives. The following items are discussed: (i) the technical parameters used to appreciate the effect of activated protein C induce a bias of interpretation, the mean intrinsic effect of activated protein C, in plasmas from women on second or third-generation oral contraceptives being strictly identical; (ii) there are no data available to show that this assay can indicate a thromboembolic risk in asymptomatic women on oral contraceptives; and (iii) this assay is a global and non-specific test, basically sensitive to the plasma concentrations of many coagulation factors which are increased or decreased by oestrogens and progestogens. For instance protein S, in which oral contraceptive-induced modifications account for the differential effect of oral contraceptives on Rosing's assay, but which modifications are not related to the thromboembolic risk of oral contraceptives. The androgenic potential of the progestogen may counteract the effect of oestrogens in the test. More generally, in such a complex situation in which there is a 'modification of the modification', there is no haemostasis-related test which provides a risk indicator for thrombosis. Based on testing of the plasma response to activated protein C, it is impossible to state that third-generation oral contraceptives induce a more important thromboembolic risk than oral contraceptives containing a more androgenic progestogen.