Free Protein S Levels Are Elevated in Familial C4b-Binding Protein Deficiency

Abstract

AbstractIn plasma, 40% of the protein S is free and functions as a cofactor for the anticoagulant effects of activated protein C. The remaining 60% of protein S is complexed to C4b-binding protein and is functionally inactive. A family with hereditary C4b binding protein deficiency has been identified with C4b-binding protein levels in an affected father and daughter of 37 µg/mL and 23 µg/mL, respectively; these values are significantly below the normal range for this protein of 180 µg/mL ± 44 µg/mL (mean ± 2 SD). The total protein S (free + bound) is normal in these individuals (23.2 µg/mL and 17.8 µg/mL, respectively; normal 19.1 µg/mL ± 6.0 µg/mL). The free protein S levels are markedly increased at 22.5 µg/mL and 17.4 µg/mL, respectively (normal 5.9 µg/mL ± 2.4 µg/mL). This experiment of nature shows that total protein S levels in plasma are not affected by the absence of C4b-binding protein and that chronic elevation of free protein S is not associated with increased hemorrhagic tendencies.