A simple functional protein S assay using PROTAC.

Protein S is the co-factor of the enzymic action of protein C on FV and FVIII. A functional assay for protein S is not readily available for clinical use; however, we have developed a functional protein S assay based on the prolongation of Russell viper venom (RVV) plasma clotting time by protein C activated by PROTAC. Based on this assay, median functional protein S (5-95th percentile) of 46 healthy individuals was 82% (60-120%). Median functional protein S of 15 cord blood samples was 58% (35-71%). Unexpectedly, we found relatively high levels of functional protein S in a group of patients on long-term warfarin therapy whose INR ranged from 1.1 to 3.9. The median functional protein S of these patients was 71% (40-101%). We demonstrated that the protein S was not decarboxylated, as was the case with protein C, in these warfarin plasmas.