PB1386 - Comparison of the ETP-based thrombomodulin assay versus the ETP-based APC resistance assay on the ST Genesia system

Background: Resistance towards activated protein C(APC) in women treated with combined hormonal contraceptive (CHC) can be measured using an endogenous thrombin potential (ETP)-based assay, ideally targeting 90% ETP inhibition in healthy individuals. The only commercially available kit for APC resistance assessment on an automated thrombin generation platform, i.e., the ST Genesia, is the STG-ThromboScreen kit which uses thrombomodulin (TM) and targets 50% ETP inhibition. Nevertheless, previous assays based on the addition of exogenous APC instead of TM are better known to assess CHC-induced APC resistance.

Aims: To compare the sensitivity of the 50% ETP-based TM resistance assay and the 90% ETP-based APC resistance assay (recently implemented) on the ST Genesia system, in women using CHCs.

Methods: The TM-based assay consisted of using STG-ThromboScreen TS-TM and STG-ThromboScreen TS+TM while the APC-based assay consisted of using the STG-ThromboScreen TS-TM in absence and presence of exogenous APC. This study involved 96 individuals which were stratified into several subgroups: healthy individuals (men and women not using CHC) (n=56), women using 2nd generation CHCs (n=18), 3rd generation CHCs (n=13) and the so-called “other” CHCs (n=9).

Results: The mean ETP inhibition % (±SD) of healthy individuals equaled 89.5%±8.1% in presence of APC, and 64.2%±12.7% in presence of TM. Differences between healthy individuals and women using CHCs were significant with both assays. No significant difference was observed among women using different CHCs generation with the TM-based assay while significant differences were observed between the “other” CHCs user group versus 2nd and 3rd generation CHCs user groups with the APC-based assay.

Conclusion(s): APC resistance test based on the addition of exogenous APC achieving 90% ETP inhibition is preferable over commercial TM-based assay targeting 50% ETP inhibition for the assessment of CHC-induced APC resistance. Further investigations are required to confirm our results and consider the use of the ETP-based APC resistance assay in clinics.