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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Screening of protein S deficiency using a functional assay in patients with venous and arterial thrombosis.

Protein S is the vitamin K-dependent cofactor of activated protein C which functions as a potent anticoagulant by degrading activated factors V and VIII in a Ca2+ and phospholipid-dependent reaction. Protein S circulates under two forms, free (approximately 40%) or bound to C4b-binding protein (C4b-bp); only the free form supports the cofactor activity for activated protein C. Total protein S antigen is usually measured by rocket immunoelectrophoresis. Free protein S antigen is measured by the same technique but after precipitation of the protein S-C4b-bp complex by PEG 8000. However, these immunological assays do not detect functional alterations of protein S which can be responsible for thrombosis. This paper describes a functional assay for free protein S based on its ability to promote the prolongation of clotting time following factor Va inactivation by activated protein C when coagulation is triggered by factor Xa. Using this assay a prolongation of about 100 s between 0 and 1 U/ml protein S is measured, allowing a reliable and rapid determination of functional protein S. The correlation coefficient between functional protein S and free antigenic protein S is 0.921. This functional protein S assay has allowed the detection of 34 cases of protein S deficiency, confirmed by immunological assays, and their classification. The striking observation is the high frequency (approximately 25%) of arterial thrombosis in these patients. The rapid determination of functional protein S in patients with venous or arterial thrombosis is of diagnostic interest and should allow the detection of mutant protein S in combination with an immunological assay.[1]

References

  1. Screening of protein S deficiency using a functional assay in patients with venous and arterial thrombosis. Wiesel, M.L., Charmantier, J.L., Freyssinet, J.M., Grunebaum, L., Schuhler, S., Cazenave, J.P. Thromb. Res. (1990) [Pubmed]
 
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