Because protein S helps activated protein C degrade clotting factors Va and VIIIa, deficiency of protein S predisposes to venous thrombosis.
Protein S, a vitamin K–dependent protein, is a cofactor for activated protein C–mediated cleavage of factors Va and VIIIa. Heterozygous deficiency of plasma protein S predisposes to venous thrombosis and is similar to heterozygous protein C deficiency in genetic transmission, prevalence, laboratory testing, treatment, and precautions. Homozygous deficiency of protein S can cause neonatal purpura fulminans that is clinically indistinguishable from that caused by homozygous deficiency of protein C. Acquired deficiencies of protein S (and protein C) occur during disseminated intravascular coagulation and warfarin therapy and in association with l-asparaginase administration.
Diagnosis is based on antigenic assays of total or free plasma protein S. (Free protein S is the form unbound to C4 binding protein.)
The treatment of protein S deficiency associated with venous thrombosis is identical to the treatment of protein C deficiency (see Protein C Deficiency), with one exception. Because there is no purified protein S concentrate available for transfusion, only normal plasma can be used to replace protein S during a thrombotic emergency.
Last full review/revision January 2013 by Joel L. Moake, MD
Content last modified November 2013