Because protein S binds and assists activated protein C in the degradation of coagulation factors Va and VIIIa, deficiency of protein S predisposes to venous thrombosis.
(See also Overview of Thrombotic Disorders.)
Protein S, a vitamin K–dependent protein, is a cofactor for activated protein C–mediated cleavage of factors Va and VIIIa. Protein S and protein C are, therefore, components of a natural plasma anticoagulant system.
Heterozygous deficiency of plasma protein S predisposes to venous thrombosis. Heterozygous protein S deficiency 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 C (and, soon thereafter, protein S) occur in patients with disseminated intravascular coagulationestrogen replacement therapy or contraception and during pregnancy due to the influence of estrogen on free protein S levels. Inflammation also influences free protein S levels. This phenomenon contributes to the hypercoagulability associated with these states.
Diagnosis is based on antigenic assays of total or free plasma protein S (free protein S is the form unbound to the protein S carrier molecule, C4-binding protein). Protein S activity can also be measured, but the assay is technically difficult and is associated with a high false-positive rate (10 to 15%) so more reproducible antigen assays are favored.
Treatment of Protein S Deficiency
Anticoagulation
The treatment of protein S deficiency associated with venous thrombosis is identical to the treatment of protein C deficiency, with one exception. Because there is no purified protein S concentrate available for transfusion, normal plasma is used to replace protein S during a thrombotic emergency.
