BACKGROUND: The evaluation of the activated protein C resistance (APCr) based on the endogenous thrombin potential (ETP) is recommended during the development of steroid contraceptives. Results are usually expressed as "normalized APC sensitivity ratio" (nAPCsr) using a reference plasma that should achieve an ETP ratio of 0.1 in presence of exogenous APC. Because of the inter-assay variability, achieving exactly an ETP ratio of 0.1 in each run is almost impossible which significantly affects the theoretical 0-10 scale of nAPCsr.
OBJECTIVES: To compare the nAPCsr to the nAPCsr10 , a newly proposed method to express the degree of APC resistance.
METHODS: Individual plasma samples (n=854) were analysed to compare nAPCsr and nAPCsr10 . These values were obtained using the validated ETP-based APCr assay.
RESULTS: The Spearman correlation between nAPCsr and nAPCsr10 had a coefficient of 0.99. Linear regression showed the following equation y = 0.9315*x + 0.03942 (r2 = 0.97). When differences (nAPCsr10 - nAPCsr) were plotted against nAPCsr10 , the mean difference equalled to 0.16 or 4.95%. The correction obtained with the use of the nAPCsr10 showed that the results of the nAPCsr were statistically different (p-value = <0.0001).
CONCLUSIONS: This new scale provides a harmonization and normalization of the nAPCsr. Results show a better reproducibility with the nAPCsr10 . It avoids the additional variability and the unharmonized scale introduced by the use of a reference plasma. This adapted method for the calculation of the APC resistance could provide the regulatory and scientific bodies with more reproducible and harmonized evaluations.