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Protein S deficiency
Protein S structure
Specialty	Hematology
Causes	Vitamin K deficiency[1]
Diagnostic method	Coagulation test[1]
Treatment	Heparin, Warfarin[2]

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. 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]}

Signs/symptoms

Among the possible presentation of protein S deficiency are:^[1][2][4]

Cause

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^[5][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

In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium^[7][8]. 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][9]

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.^[5]

Diagnosis

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][10][11]

• Protein S antigen test


• 
  Coagulation test (prothrombin time test)


• 
  Thrombotic disease investigation


• 
  Factor V Leiden test

Differential diagnosis

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)^[2]

Types

There are three types of hereditary protein S deficiency:^[2][5]

• 
  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)

Treatment

Dabigatran

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^[1]):^[2][9]

• Unfractionated heparin (w/ warfarin)


• LMWH/Low molecular weight heparin


• Dabigatran


• Direct Factor Xa Inhibitors


• Graduated compressed stocking


• High degree of prophylaxis
  

References

Further reading

• 
  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.
  

External links

Wikimedia Commons has media related to Thrombosis.

• 
  Protein S deficiency at Curlie