Combined oral contraceptives-induced coagulopathies
: Evaluation of the prothrombotic state using a global coagulation assay

Student thesis: Doc typesDoctor of Biomedical and Pharmaceutical Sciences


22,000 cases of thrombosis occur each year in Europe following the use of combined oral contraceptives (COCs). One of the major challenges for healthcare professionals is to identify women at risk. The assessment of activated protein C (APC) resistance, a dysregulation of haemostasis, could shed some light on this issue.
Although several methods for APC resistance detection have been developed, the endogenous thrombin potential (ETP)-based APC resistance assay has proven to be the most suitable for the assessment of COC-induced changes on the coagulation system.
The objective of this thesis is to demonstrate the analytical performances of the ETP-based APC resistance assay as well as its interest in the routine care to characterize the thrombotic risk of women on hormonal contraception.
The first step consisted in validating the methodology, according to regulatory requirements in terms of analytical performances. Then, considering its screening potential, we implemented the ETP-based APC resistance assay on an automated platform. Indeed, making it available in clinical routine would make the test accessible to prescribers and patients.
In a second step, we created exploratory models to predict the thrombotic risk according to the level of APC resistance for specific COC preparations. The thrombotic risk differs depending on the oestrogen-progestin association and these models showed that these differences could be captured through the ETP-based APC resistance assay. So far, results show that COCs which do not contain ethinylestradiol, but rather oestradiol or estetrol, express lower APC resistance level, in line with the lower risk of thrombosis.
These findings support the concept that the ETP-based APC resistance, when evaluated by a standardized validated methodology, could serve as a surrogate biomarker to estimate the thrombotic risk of a particular COC.
Date of Award6 Jun 2023
Original languageEnglish
Awarding Institution
  • University of Namur
SponsorsRegion Wallonne
SupervisorJonathan Douxfils (Supervisor), Jean-Michel Dogne (Co-Supervisor), Bernard Masereel (Jury), Francois Mullier (Jury), Philippe Hainaut (Jury), Ulysse J. Gaspard (Jury), Jean-Michel Foidart (Jury) & Jean-François Arnal (Jury)

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