Protein S deficiency D68.5

Autosomal-dominantly inherited (analogous to protein C deficiency) or acquired disease associated with reduced fibrinolytic activity and an increased risk of thrombosis due to a lack of protein S. In the hereditary form, mutations in the protein S-alpha gene (PROS1 gene) are present. Up to now > 100 different mutations in the PROS1 gene have been described.

The protein S deficiency is divided into 3 groups:

• Type I: The activity and the total and free antigen (concentration) are reduced.
• Type II: The activity is reduced, free and total antigen are normal.
• Type III: The activity as well as the free antigen are reduced, the total antigen is normal (C4B binding protein is increased.

The prevalence in the normal population is approx. 0.03 - 0.13%; in patients with thrombophilia (increased tendency to thrombosis) it is 5 - 15%.

Protein S is a vitamin K-dependent plasma protein that acts as a cofactor in the activation of protein C. Protein S alone has no influence on a clotting process. Together in complex with Protein C, Protein S accelerates the effect of Protein C due to its extremely high affinity for negatively charged phospholipid surfaces. 60% of the protein S in plasma is bound to the complement binding protein C. 40% circulate in free form. The free and the bound form can be determined separately. Heterozygous deficiencies are detectable in 2-5% of thrombosis patients.

In addition to hereditary deficiency, protein S deficiency can also be caused by exogenous factors:

• Liver diseases, so that synthetic weakness
• Waste in acute respiratory distress syndrome (ARDS)
• Cirrhosis of the liver
• Coumarin therapy
• Asparaginase therapy
• Consumption coagulopathy
• Sepsis
• Chronic inflammatory bowel disease
• Viral infections.

Congenital protein S deficiency is an autosomal-dominant inherited disease (analogous to protein C deficiency) that is associated with a significantly increased risk of thrombosis. Mutations in the protein S-alpha gene (PROS1 gene) are present. Up to now > 100 versch. mutations in the PROS1 gene have been described.

The molecular weight of the protein S is 69,000 D. The plasma concentration of the total protein is 20-25 mg/l or 60-120%. The free protein S is 7-10 mg/l, corresponding to an activity of 23-49 mg/l of the total protein. The half-life is 42.5 hours. Apart from the liver, synthesis takes place in the endothelium and megakaryocytes.

1. HA Neumann (2014) The coagulation system. ABW Scientific Publisher GmbH Berlin S. 220f