Protein S deficiency
|Protein S deficiency|
|Classification and external resources|
Protein S deficiency is a disorder associated with increased risk of venous thrombosis. Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activated protein C in the proteolytic degradation of factor Va and factor VIIIa. Decreased (antigen) levels or impaired function (activity) of protein S leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis. Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while the remaining 40 percent is free. Only free protein S has activated protein C cofactor activity.
There are three types of hereditary protein S deficiency:
- Type I - decreased protein S activity: decreased total protein S (=both bound and free protein S) levels AND decreased free protein S levels (quantitative defect)
- Type II - decreased protein S activity: normal free protein S levels AND normal total protein S levels (qualitative defect)
- Type III - decreased protein S activity: decreased free protein S levels AND normal total protein S levels (quantitative defect)
Protein S deficiency can also be acquired due to vitamin K deficiency or treatment with warfarin, systemic sex hormone therapy and pregnancy, liver disease, and certain chronic infections (for example HIV). Vitamin K deficiency or treatment with warfarin generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis. Protein S deficiency is the underlying cause of a small proportion of cases of disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT) and pulmonary embolism (PE).
- Protein S Deficiency And Thrombophilia at proteinsdeficiency.com
- Protein S Deficiency—University of Illinois
ten Kate M, Mulder R, Platteel M, Brouwer J, van der Steege G, van der Meer J (2006). "Identification of a novel PROS1 c.1113T-->GG frameshift mutation in a family with mixed type I/type III protein S deficiency". Haematologica 91 (8): 1151–2. PMID 16885060.