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
Protein S exists free (40%) or bound (60%) to complement C4 B-binding protein, but it is the free protein S that interacts with activate protein C and tissue factor pathway inhibitor and regulates coagulation, and when deficient impairs coagulation regulation in increasing the risk of thrombosis.
Protein deficiency is defined as plasma protein S antigen of less than 60% and is associated with a 2-5 fold increase of venous thromboembolism.
Protein S deficiency may be inherited or acquired.
Hereditary protein S deficiency is a rare autosomal disorder caused by variants in the PROS1 gene, located on chromosome three.
Thrombosis associated with protein S deficiency typically occurs at young age and increases by acquired factors, such as hormone therapy, pregnancy, surgery, trauma, and immobility.
Thrombosis and protein S deficiency may occur in unusual sites-axillary, mesentery or cerebral veins.
Arterial thrombosis, including acute ischemic, stroke, and arterial occlusion has been reported [in some families.
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.
Treatment
Unfractionated heparin
LMWH/Low molecular weight heparin
Dabigatran
Direct Factor Xa Inhibitors
Graduated compressed stocking
High degree of prophylaxis