Birth control pills: anticipating the risk of thrombosis for safer prescribing

Venous thrombosis is one of the most serious complications associated with combined oral contraceptives. While this risk is low overall in the general population, it increases significantly in women with specific genetic mutations, such as Factor V Leiden or the G20210A prothrombin mutation, which affects 5 to 7% of the Caucasian population.  

"Most people with genetic mutations that promote coagulation disorders are unaware of this because they are not systematically screened. The actual risk of thrombosis when prescribing birth control pills is therefore underestimated for these patients," explains Laure Morimont, a researcher at the Clinical Pharmacology and Toxicology Research Unit (URPC) and head of this research.  

As part of her doctoral research, Laure Morimont—under the supervision of Professor Jonathan Douxfils (Director of the URPC and member of the Department of Pharmacy)—has been working on the development of a blood test to assess the risk of thrombosis associated with taking the contraceptive pill. This test, known as nAPCsr (Normalized Activated Protein C Sensitivity Ratio), measures the degree of resistance to activated protein C, a natural inhibitor of coagulation. 

By cross-referencing the nAPCsr of a sample of patients taking oral contraceptives with data on the actual risk of thrombosis from pharmacovigilance studies, Laure Morimont's team was able to develop and validate a robust prediction model demonstrating a significant correlation between the thrombotic risk estimated by the nAPCsr for a given pill and the actual incidence of thrombosis observed in the population. 

Based on this model and the established reference thresholds, the nAPCsr can then be used to assess a patient's individual risk profile. The test generates a score ranging from 0 to 10, allowing the patient to be ranked in relation to these reference values and her eligibility for a given contraceptive pill to be assessed. "If the test results remain within the reference standards, the patient is considered eligible for any contraceptive pill and the doctor can safely prescribe the desired one. On the other hand, if her score deviates from these standards, the doctor can carry out a more thorough assessment or refer the patient to a pill considered to be less risky. Ultimately, our goal is to help the medical profession in its choice of prescription," emphasizes Laure Morimont. 

Currently available in several hospitals in Wallonia at a cost of approximately €70, the test is currently under discussion with a view to partial or total reimbursement by health insurance companies. 

The result of six years of research, the work of the URPC team has just been published in Research and Practice in Thrombosis and Haemostasis (RPTH), a journal of the International Society on Thrombosis and Haemostasis (ISTH), an international learned society specializing in thrombosis and hemostasis. 

This publication will also serve as the basis for efforts underway with the European Medicines Agency to recognize this test as an official biomarker. 

At the same time, Laure Morimont and her team are continuing their efforts to raise awareness among general practitioners and gynecologists in Wallonia, with the aim of making the test known to a wider range of patients. The nAPCsr is also set to be used outside Belgium, thanks to a collaboration initiated with a hospital in France.