Increased contact system activity three months after starting combined oral contraceptives

Combined oral contraceptives (COC) are associated with an increased risk of venous thromboembolism (VTE). The contact system (CAS) can, when activated, stimulate coagulation, and may play a role in thrombus formation. Our recent case-control study showed increased CAS capacity and in vivo activity in COC users, indicating a systemic activation that could contribute to VTE risk during COC treatment. Aim This study investigates intraindividual changes in CAS in women before and after start of COC treatment.

Twenty-four women aged between 15 and 34 years, who were starting treatment with COC, were included in the study. A baseline blood sample was drawn before start of COC, and a follow-up blood sample 3-4 months later. The capacity and activity of CAS, i.e. factor XII (FXII), prekallikrein (PK), H-kininogen (HK), C1-esterase inhibitor (C1inh), cleaved HK (cHK) and endogenous kallikrein potential (EKP), were analyzed.

Our study showed significantly increased levels of FXII (median 29.4 vs 42.9 mg/L; p < 0.0001) and decreased levels of C1inh (0.21 vs 0.20 g/L; p = 0.005). Increased EKP (1859 vs 2203 nmol/L*min; p = 0.0004) demonstrated an increased capacity of CAS, and increased levels of cHK (0.70 vs 0.96 μg/L; p < 0.0001) indicated an increased activity of CAS in vivo. The levels of PK and HK showed no significant changes.

This study demonstrates an increased intraindividual CAS capacity as well as an increased CAS activity during treatment with COC supporting the previous research. These effects on CAS may contribute to the increased thrombotic risk caused by COC.