Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk

Abstract

Combined oral contraceptives (COCs) induce several changes in the levels of coagulation factors. The levels of procoagulant factors are often increased, while levels of anticoagulant factors are decreased. Fibrinolysis is also affected, even if the effect seems to be more counterbalanced by opposite regulation of profibrinolytic and antifibrinolytic factors. These effects on hemostasis are more pronounced with third- or fourth-generation COC compared with second-generation COC. Venous thromboembolism (VTE) risk increases when multiple risk factors, including genetic and environmental, are present simultaneously. COC use causes changes in coagulation that modify the prothrombotic state induced by preexisting hemostatic alterations in a supra-additive manner. Therefore, testing appears to be of importance not only before implementing COC but also to monitor any potential thrombogenicity induced by COC therapy. Inherited genetic factors, such as factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C or protein S deficiencies, non-O blood group, as well as CYP2C9*2 and the rs4379368 mutations, have all been identified as genetic predictive risk factors of VTE in women. Nevertheless, the screening of these genetic biomarkers is not capable of assessing the phenotypic expression of the risk. This review will focus on the different options for screening the thrombogenic status in this population. Specific attention will be given to the endogenous thrombin potential-based activated protein C resistance, a test aiming at assessing the thrombogenicity induced by hormonal therapies and inherited or acquired thrombophilia.

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

“…These data revealed the usefulness of this prognostic device and reopened the reflection of performing biological investigations before introduction of a contraceptive method ( 114 ). Although this method is promising, the algorithm does not take into account a deficiency of protein S, protein C or antithrombin and in addition, many users of COCs developing VTE do not have a recognized hereditary coagulation problem but show instead a high responsiveness to estrogenic compounds ( 118 ). An interesting approach would be to have one or several biomarkers to establish the “coagulability status” of the patient, revealing phenotypic rather than just genotypic particularities.…”

2021 Eberhard F. Mammen Award Announcements: Part II—Young Investigator Awards

“…The most recent arising publications are also listed in the reference list for the benefit of the readership. 2 3 4 5 6 7 8 9 10 11 12 13 I have mentioned several times my personal gratification that most of the papers from earlier years have subsequently appeared in several annual top 100 listings. Of further interest, some of these papers or the young investigators themselves have subsequently won one of the most popular awards (see Table 1 for a list of prior editorials on these awards).…”

Low Thrombin Generation in Users of a Contraceptive Containing Estetrol and Drospirenone

“…Pregnancy and the use of CHCs cause changes in plasma levels of almost all proteins involved in the coagulation and fibrinolysis ( 12 ). These changes might be considered relatively modest when measured separately, but they could have a supra-additive effect leading to a procoagulable state responsible for this increased risk of VTE ( 13 ).…”