Laboratory diagnosis of inherited protein S deficiency

The authors investigated assays for free protein S (ProS) antigen, total ProS antigen, and ProS crossed immunoelectrophoresis (CIEP) in the diagnosis of type 1 inherited ProS deficiency. Accurate measurement of the hemostatically important free ProS required showing that, on each specimen, precipitation of the C4b-binding protein (C4b-BP)/protein S complex (C4b-BP/ProS) by polyethylene glycol-8,000 (PEG) was complete. The authors showed this by doing a ProS CIEP on the same PEG supernate that was used for quantitative measurement of free ProS. The +/- 2 standard deviation (+/- 2 SD) ranges for free ProS were 81-133% for males and 50-130% for females. This striking male-female difference has been reported only twice before. With the use of a graph of values for free ProS versus prothrombin time (PT), patients with inherited ProS deficiency segregated cleanly from normals and from patients on warfarin therapy without ProS deficiency until the PT was greater than 20 seconds. There is overlap of total ProS antigen values between normals and patients with inherited ProS deficiency.