Protein S Deficiency

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

Signs and symptoms

Among the possible presentation of protein S deficiency are:

Cause

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)

Pathophysiology

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.

Diagnosis

The diagnosis for deficiency of protein S can be done via reviewing family history of condition and genetic testing, as well as the following:
* 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)

Types

There are three types of hereditary protein S deficiency:
* ''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

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):
::::::*Unfractionated heparin (w/ warfarin)
::::::*LMWH/Low molecular weight heparin
::::::*Dabigatran
::::::*Direct Factor Xa Inhibitors
::::::*Graduated compressed stocking
::::::*High degree of prophylaxis

References

Further reading

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External links

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{{Diseases of megakaryocytes, us=y

Coagulopathies