Protein S deficiency
|Protein S deficiency|
|Protein S structure|
|Causes||Vitamin K deficiency|
|Diagnostic method||Coagulation test|
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 activate protein C in the degradation of factor Va and factor VIIIa. 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. 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 terms of the cause of protein S deficiency it can be in inherited via autosomal dominance. A mutation in the PROS1 gene triggers the condition. The cytogenetic location of the gene in question is chromosome 3, specifically 3q11.1 Protein S deficiency can also be acquired due to vitamin K deficiency, treatment with warfarin, liver disease, and acute thrombosis (antiphospholipid antibodies may also be a cause as well)
In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium. 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.
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.
- Protein S antigen test
- Coagulation test (prothrombin time test)
- Thrombotic disease investigation
- Factor V Leiden test
Among the possibilities for differential diagnosis of protein S deficiency are- Antiphospholipid syndrome, disseminated intravascular coagulation and antithrombin deficiency (though this list is not exhaustive)
- Type I – decreased protein S activity: decreased total protein S levels, as well as decreased free protein S levels
- Type II – decreased in regards to the cofactor activity of the protein
- Type III – decreased protein S activity: decreased free protein S levels (normal total protein S levels)
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 inherited homozygotes is usually in line with a higher incidence of thrombosis for the affected individual):
- "Protein S Deficiency. Learn about Protein S Deficiency | Patient". Patient. Retrieved 2016-10-16.
- "Protein S Deficiency: Background, Pathophysiology, Epidemiology". 2016-05-02. Cite journal requires
- "Protein S: Reference Range, Collection and Panels, Interpretation". 2016-06-01. Cite journal requires
- "Congenital protein C or S deficiency: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 16 October 2016.
- Reference, Genetics Home. "PROS1 gene". Genetics Home Reference. Retrieved 16 October 2016.
- Reference, Genetics Home. "protein S deficiency". Genetics Home Reference. Retrieved 16 October 2016.
- "Endothelial Cells, Volume 1, 1988, p158, By Una S." books.google.co.uk. Retrieved 24 January 2019.
- Burstyn-Cohen, T.; Heeb, M. J.; Lemke, G. (2009). "J Clin Invest. 2009 Oct, 119(10):2942-53, Burstyn-Cohen T1, Heeb MJ, Lemke G: Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis". The Journal of Clinical Investigation. 119 (10): 2942–53. doi:10.1172/JCI39325. PMC 2752078. PMID 19729839.
- Ten Kate, M. K.; Van Der Meer, J. (1 November 2008). "Protein S deficiency: a clinical perspective". Haemophilia. 14 (6): 1222–1228. doi:10.1111/j.1365-2516.2008.01775.x. ISSN 1365-2516. PMID 18479427.
- "Protein S blood test: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 16 October 2016.
- "Protein S deficiency - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 16 October 2016.
- 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.
- García de Frutos, Pablo; Fuentes-Prior, Pablo; Hurtado, Begoña; Sala, Núria (17 October 2007). "Molecular basis of protein S deficiency". Thrombosis and Haemostasis. 98 (3): 543–56. doi:10.1160/TH07-03-0199. hdl:10261/89408. ISSN 0340-6245. PMID 17849042. Retrieved 16 October 2016.
- 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. ISSN 1899-5276. PMID 23986205.
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