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Protein C and S Immunoassay

I’ve never understood why protein C and protein S immunoassay results are reduced in Warfarin therapy. Because Warfarin reduces gamma-carboxylation of protein C and protein S glutamic acid units, we expect there to be reduction in activity assays but it turns out that immunoassay results are also proportionally reduced. 
Stephen Duff of Precision BioLogic asked me this question last week, driving me to my Colman, Kitchens, and even Esoterix’ Coagulation Handbook. They had nothing, so I turned to manufacturers’ package inserts. Most state the immunoassay results are reduced in Warfarin therapy, in particular the free protein S assay, but none says why, nor gives a reference.

You would think the immunoassay would remain near the normal range since we still produce protein C and protein S molecules, albeit non-carboxylated (called proteins in vitamin K antagonism, or PIVKA), but somehow the des-carboxy protein C and protein S molecules are not measured.

If anyone has an insight, please send a response here. For more on protein C and S, go to our educational module series, Laboratory Detection of Thrombosis Risk. Thanks. Geo.

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