What is Protein S Deficiency? Simple Answers to Basic Questions

Protein S deficiency is a blood clotting disorder that predisposes patients to excessive blood clots in the veins. It is a rare condition: The incidence of protein S deficiency in the general population has been estimated at 0.2%. Protein S deficiency can be hereditary or acquired, mild and asymptomatic or severe and life-threatening. It can also be quantitative or qualitative. In the quantitative defect, there is not enough protein S to regulate blood clotting. In the qualitative defect, there is a normal amount of protein S, but it does not function properly.

2) What is protein S and what does it do?

Protein S is a vitamin K-dependent plasma glycoprotein that acts as a natural anticoagulant, i.e. a natural blood thinner. It circulates in plasma in two forms: a free form (40% of total protein S) and a bound form (60% of total protein S).

Protein S is best known for its role as cofactor (read: sidekick) to Protein C (PC), another important naturally occurring anticoagulant. The role of protein C is to inactivate clotting factors Va and VIIIa (the "a" next to the Roman numeral stands for "activated"). Protein S combines with activated PC (aPC) and enhances its anticoagulant action as much as tenfold.

3) Where is protein S produced?

Protein S is mainly, but not exclusively, produced in the liver. It is called "vitamin K-dependent" because vitamin K is necessary for its synthesis.

4) What causes protein S deficiency?

Hereditary protein S deficiency is caused by various genetic mutations. Causes of acquired protein S deficiency include kidney disease, vitamin K deficiency, liver disease, treatment with warfarin (= anticoagulant and vitamin K antagonist), sickle cell anemia, acute thrombosis, autoimmune disease, chronic infection (e.g. HIV), disseminated intravascular coagulation (DIC), etc. Levels of protein S are reduced during pregnancy, and also as a result of certain types of hormone replacement therapy (HRT) and oral contraceptives.

5) What are the symptoms of protein S deficiency?

Symptoms commonly associated with protein S deficiency are deep vein thrombosis (especially of the legs), thrombophlebitis, and pulmonary embolism. Thrombosis under the age of 55 years or recurrent thrombotic episodes may also point to protein S deficiency. It is estimated that up to 80% of heterozygous patients will develop venous thromboembolism. Homozygous patients are at high risk for life-threatening purpura fulminans and DIC. Several risk factors exacerbate the predisposition to thrombosis: these include infection, trauma, inflammation, pregnancy and postpartum, smoking, surgery, immobilization, HRT therapy, oral contraceptives, etc.

6) How is protein S deficiency diagnosed?

Special blood tests measure the amount of protein S (free, bound, and total) in plasma as well as its anticoagulant function.

7) How is protein S deficiency treated?

Protein S deficiency is treated with anticoagulant drugs. In managing protein S deficiency, the physician's main consideration is the patient's level of risk for thrombosis, depending on the severity of the defect and the specific symptoms (e.g. one-time vs. recurrent thromboembolic episodes, protein S deficiency vs. multiple deficiencies, family history, additional risk factors, etc.). Long-term anticoagulation comes with risks of its own, so the physician will weigh these risks against the probability of recurrent thrombosis. In asymptomatic carriers of protein S deficiency, the physician's goal is to prevent the first thrombosis. Again, there is no "one prescription fits all" scenario, and it is up to the coagulation specialist to make treatment decisions on an individual basis.

As with any medical condition, if you suspect you may have a blood disorder, please consult your doctor asap.

Sources:
http://emedicine.medscape.com/article/205582-overview
http://www.med.illinois.edu/hematology/PtProtS.htm
http://www.labtestsonline.org/understanding/analytes/protein_c_and_s/glance.html
http://www.stoptheclot.org/News/article137.htm