Predicting venous thromboembolism risk from endogenous thrombin potential-based normalized activated protein C sensitivity ratio assay: toward early assessment of combined oral contraceptives

Background: Combined oral contraceptives (COCs) increase venous thromboembolism (VTE) risk, depending on estrogen type, dose, and progestin. While epidemiological studies provide insight into these risks, they require years to complete. The normalized activated protein C sensitivity ratio (nAPCsr), a standardized assay of acquired activated protein C resistance, has emerged as a potential biomarker of COC-induced VTE risk. Objectives: model predicting VTE risk associated with various COC formulations based on their mean nAPCsr values. Methods: , Spearman's rank correlation coefficient, and the root mean square error, and performed a sensitivity analysis by excluding COC nonusers. We then estimated population-based VTE risks for the 4 COCs not used in model construction. Results: = .96; root mean square error = 0.21; Spearman correlation coefficient = 1) and remained robust despite group size imbalance. Predicted VTE risks for ethinylestradiol 30 μg with dienogest 2 mg, ethinylestradiol 20 μg with drospirenone 3 mg, estradiol 1.5 mg with nomegestrol acetate 2.5 mg, and estetrol 15 mg with drospirenone 3 mg were 4.36, 3.43, 1.50, and 1.45, respectively, consistent with or complementary to existing epidemiological evidence. Conclusion: Our model, based on mean nAPCsr, provides a reliable, biomarker-based approach for predicting population-based COC-related VTE risk. This strategy could help shorten the time between product launch and population-based risk assessment.