Protein S deficiency is an autosomal dominant disorder characterized by decreased levels of plasma protein S antigen or activity. Protein S is a vitamin K-dependent plasma protein that inhibits blood clotting by serving as a cofactor for activated protein C (also a vitamin K-dependent protein), and exists in 2 forms in plasma: the free, functionally active form and the inactive form complexed with C4b-binding protein. Three types of protein S deficiency have been described according to the levels of total and free protein S antigen, as well as APC cofactor activity, in plasma. In type I or quantitative protein S deficiency, total and free protein S antigen values are decreased together with reduced anticoagulant activity. In type III or free PROS1 deficiency, free PROS1 antigen and PROS1 activity levels are reduced, whereas total PROS1 antigen levels are normal. In the rare type II or qualitative protein S deficiency, only the APC cofactor activity is reduced. The disorder is associated with recurrent venous thrombosis and pulmonary embolism. In some rare cases, thrombosis can be found at unusual sites, like the axillary, mesenteric, and cerebral veins. Protein S deficiency is found in 2-3% of patients with thromboembolism and has an incidence of 1 in 5,000.
Protein S deficiency is caused by mutations in the protein S gene (PROS1), mapping to 3p11.1.