Protein S Deficiency

Excerpt

Protein S deficiency is a rare disorder characterized by reduced activity of protein S, a plasma serine protease with complex roles in coagulation, inflammation, and apoptosis. Protein S is an anticoagulant protein discovered in Seattle, Washington, in 1979 (hence the name); it facilitates the action of activated protein C (APC) on activated factor 5 (F5a) and activated factor 8 (F8a). A deficiency in protein S characteristically demonstrates the inability to control coagulation, resulting in the excessive formation of blood clots (thrombophilia) and venous thromboembolism (VTE). Protein S deficiency can be hereditary or acquired. The acquired deficiency is usually due to hepatic disease, nephrotic syndrome, or vitamin K deficiency. Hereditary protein S deficiency is an autosomal dominant trait. Thrombosis is observed in both heterozygous and homozygous genetic deficiencies of protein S.

Protein S deficiency usually manifests as VTE and any association between protein S deficiency and arterial thrombosis appears coincidental or weak. There is minimal evidence for arterial thrombosis in other forms of hereditary thrombophilias, such as protein C deficiency, antithrombin 3 deficiency, or factor V Leiden.