Protein S deficiency is a disorder associated with increased risk of venous thrombosis.[1]Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein C in the degradation of factor Va and factor VIIIa.[3]
Decreased (antigen) levels or impaired function of protein S leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis. Some risk factors for deep vein thrombosis or pulmonary embolism in patients with protein S deficiency include pregnancy, older age, hormonal therapy, consumption of birth control pills, recent surgery, trauma, and physical inactivity.[4] 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[medical citation needed]
In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium.[8][9] Protein S is a cofactor of APC both work to degrade factor V and factor VIII. It has been suggested that Zn2+ might be necessary for Protein S binding to factor Xa.[2][10]
Mutations in this condition change amino acids, which in turn disrupts blood clotting. Functional protein S is lacking, which normally turns off clotting proteins, this increases risk of blood clots.[6]
The diagnosis for deficiency of protein S can be done via reviewing family history of condition and genetic testing, as well as the following:[1][11][12]
In terms of treatment for protein S deficiency the following are consistent with the management (and administration of) individuals with this condition (the prognosis for inheritedhomozygotes is usually in line with a higher incidence of thrombosis for the affected individual[1]):[2][10]
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. PMID16885060.
Wypasek, Ewa; Undas, Anetta (1 August 2016). "Protein C and protein S deficiency - practical diagnostic issues". Advances in Clinical and Experimental Medicine. 22 (4): 459–467. ISSN1899-5276. PMID23986205.
