Resistance to activated protein C in women using oral contraceptives

Resistance to activated protein C (APC resistance) is an important and comm on risk factor for deep vein thrombosis. The majority of patients with APC resistance carry a mutation on the factor V gene at nucleotid position 1691 (G/A), called factor V Leiden mutation, Besides the factor V Leiden mutati on several acquired risk factors like lupus anticoagulant, elevated levels of acute phase proteins (increased plasma levels of factor VIII and fibrino gen), pregnancy, or the use of oral contraceptives are known to induce APC resistance in plasma. We studied the effect of oral contraceptives (OC) on hemostasis variables known to be risk factors for venous thromboembolism, e specially looking for acquired APC resistance and the plasmatic factors of the protein C system, We studied 821 women, who were randomly selected and enrolled in the BATER- cohort study (Bavarian Thromboembolic Risk Study), w hich was carried out in Bavaria (Germany) from 1996 to 1997, Current use of any OC type compared with noncurrent use showed a significantly impaired r esponse to APC, There was no difference in APC response among women current ly using OCs of different generations. Coagulation factor VIII was the only factor of the protein C pathway that was not altered under OC use. All oth er plasmatic factors of the protein C system changed in the expected range as described before. On the other hand, coagulation factor VIII was the onl y factor of the protein C system which negatively correlated with the APC r esponse in the assays applied. Thus, APC resistance is significantly lower in OC users than in nonusers but cannot be attributed to increased factor V III levels, Whether a decreased response to APC in OC users is of clinical relevance has to be proven in further studies.