Protein S

Protein S (PS) is one of the vitamin K-dependent coagulation proteins and is synthesized in the liver as an inactive precursor. The active form is obtained after carboxylation of glutamic residues by a vitamin K-dependent carboxylase, thus allowing the molecule to bind calcium ions. Unlike the other clotting factors in this family, however, PS is not a zymogen of a serine proteinase.

Two forms of PS are present in plasma - free PS (40%) and PS bound to the Complement C4-Binding Protein (C4BP; 60%). The two forms are in dynamic equilibrium, but only the free form has biologic activity. PS acts as a cofactor in the activation of Protein C by thrombin that has become bound to Thrombomodulin on the endothelial cell membrane. PS is therefore important for the ability of Protein C to downregulate thrombin generation through cleavage of activated factors V and VIII.

Congenital deficiency of PS is associated with an increased risk of developing venous thromboembolism. Acquired deficiency of PS may occur during acute phase reactions and pregnancy, when more of the plasma PS is bound to C4BP and is therefore functionally inactive. The diagnosis of congenital PS deficiency should never be made while the patient is on coumadin or pregnant.

The PS Activity assay is based upon the cofactor activity of PS which is enhances the anticoagulant action of activated Protein C. This enhancement is reflected by the prolongation of the clotting time of a system enriched with Factor Va which is a physiological substrate for activated Protein C.

PS antigen (free and total) is determined with a latex-enhanced immunassay.

We recommend that low (<60%) values are always repeated on a fresh plasma sample and that the levels of free (not bound to C4BP) and total PS (sum of bound and free) protein be determined by immunoassay.

Normal ranges:

Protein S Activity: 62 - 121%
Protein S Antigen (Free): 70 - 160%
Protein S Antigen (Total): 70 - 160%