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 VIII



Decreased 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.



Among the possible presentation of protein S deficiency are:



Thrombosis of lower extremities



Superficial thrombophlebitis



Redness in affected area



Purpura fulminans



Human Chr 3



Mild protein S deficiency is estimated to occur in approximately 1 in 500 individuals. 



Severe protein S deficiency is rare; however, its exact prevalence is unknown.



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. 



Protein S deficiency can be acquired due to vitamin K deficiency, treatment with warfarin, liver disease, and acute thrombosis, and antiphospholipid antibodies may also be a cause as well.



Protein S is made in liver cells and the endothelium.



It is a cofactor of APC both work to degrade factor V and factor VIII. 



Mutations change amino acids, which disrupts blood clotting: functional protein S which normally turns off clotting proteins is lacking 


increasing  risk of blood clots.



The diagnosis for deficiency of protein S is suggested by family history.



Protein S antigen test is available.



Differential diagnosis: Antiphospholipid syndrome, disseminated intravascular coagulation and antithrombin deficiency.



Three types of hereditary protein S deficiency exist:



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 and normal total protein S levels.






Unfractionated heparin 



LMWH/Low molecular weight heparin






Direct Factor Xa Inhibitors



Graduated compressed stocking



High degree of prophylaxis



Leave a Reply

Your email address will not be published. Required fields are marked *