Protein S deficiency

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Protein S deficiency
Protein PROS1 PDB 1z6c.png
Protein S
Classification and external resources
Specialty hematology
ICD-10 D68.5
ICD-9-CM 289.81
OMIM 176880
DiseasesDB 10814
eMedicine med/1924
Patient UK Protein S deficiency
MeSH D018455

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.[2] 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]

Types[edit]

There are three types of hereditary protein S deficiency:[3][4]

  • 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)

Signs/symptoms[edit]

Among the possible presentation of protein S deficiency are:[1][3][5]

Cause[edit]

Human Chr 3

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[4][6] 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)[1]

Pathophysiology[edit]

In regards to the mechanism of protein S deficiency we should start by indicating that,Protein S is principally made in liver cells. 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.[3][7]

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.[4]

Diagnosis[edit]

PTT blood tests Vacutainer tube

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][8][9]

Differential diagnosis[edit]

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)[3]

Treatment[edit]

Dabigatran

In terms of treatment for protein S deficiency the following are consistent with the management (and administration of) individuals with this condition ( it should be noted that the prognosis for inherited homozygotes is usually in line with a higher incidence of thrombosis for the affected individual[1]):[3][7]

References[edit]

  1. ^ a b c d e "Protein S Deficiency. Learn about Protein S Deficiency | Patient". Patient. Retrieved 2016-10-16. 
  2. ^ "Protein S: Reference Range, Collection and Panels, Interpretation". 2016-06-01. 
  3. ^ a b c d e "Protein S Deficiency: Background, Pathophysiology, Epidemiology". 2016-05-02. 
  4. ^ a b c Reference, Genetics Home. "PROS1 gene". Genetics Home Reference. Retrieved 16 October 2016. 
  5. ^ "Congenital protein C or S deficiency: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 16 October 2016. 
  6. ^ Reference, Genetics Home. "protein S deficiency". Genetics Home Reference. Retrieved 16 October 2016. 
  7. ^ a b 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. Retrieved 16 October 2016. 
  8. ^ "Protein S blood test: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 16 October 2016. 
  9. ^ "Protein S deficiency - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 16 October 2016. 

Further reading[edit]

  • 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: 543–56. doi:10.1160/TH07-03-0199. 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.