[5][9] The initiation phase accounts for less than 5% of total thrombin generation, making aPTT-based tests poorly indicative of hypercoagulability in general.
[10][11] The aPTT-based assay is more sensitive to levels of prothrombin and factor VIII, whereas the ETP-based test is more sensitive to levels of tissue factor pathway inhibitor (TFPI) and protein S.[5] The ETP-based test has traditionally been performed using methods such as the calibrated automated thrombogram (CAT) and has been limitedly available due to its technical difficulty.
[13][14][5][4][2][15] Pregnancy[7] and ethinylestradiol (EE)-containing combined birth control pills increase APC resistance as measured by either the aPTT- or ETP-based test.
[14] Increased APC resistance with both the aPTT-based and ETP-based tests has been observed with feminizing hormone therapy in transgender women, which involves higher doses of estradiol than are used in other contexts.
[21] By 2020 however, a validated methodology was developed aiming to propose a standardized and harmonized scale for ETP-based APC resistance, the normalized activated protein C sensitivity ratio (nAPCsr).