The APC-PCI concentration as an early marker of activation of blood coagulation: A study of women on combined oral contraceptives

BackgroundThe risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of”thrombogenicity” has not been identified.ObjectivesTo investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C ( APC-PCI) and on comparable hemostatic factors in fertile women.MethodForty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30 μg ethinylestradiol and 150 μg levonogestrel (LNG/EE) or a preparation containing 30 μg ethinylestradiol and 150 ug desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles.ResultsThe plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p < 0,01).The plasma concentration of D-dimer did not increase during OC treatment.ConclusionThe APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation.