Protein S.

Protein S.


La proteina S it is an important anticoagulant factor, normally present in the blood.

Quest'element cooperates with the coagulative protein C during the process of clot formation, controlling its extension and counteracting the tendency to develop thromboembolic phenomena.

Il plasma dosage of protein S allows identification of acquired and congenital deficiencies. A deficiency in this parameter can result, for example, from liver failure, anticoagulant treatment, vitamin K deficiency, estrogen-progestogen intake or high levels of estradiol to induce ovulation.


Protein S is a plasma protein that participates in coagulation process: cooperating with other factors, this element has the task of counteract thrombosis (understood as excessive clotting activity), keeping the blood fluid. In other words, protein S is a physiological anticoagulant.

For this reason, a quantitative alteration or dysfunction of this anticoagulant protein represents a risk factor for thromboembolic events.

Protein S is synthesized in liver and in endothelial cells; its production is vitamin K dependent.

Variants of protein S: free form and bound form

In the bloodstream, protein S is present both in free (about 40%) and bound (60%) form:

  • La free form of protein S is the variant ACTIVE and serves as a cofactor for protein C;
  • La bound form of protein S is the variant INACTIVE; it is found in plasma in a form associated with the C4b binding protein (C4b carrier molecule, regulatory component of the complement system).


Protein S is the main natural cofactor for protein C, activated in the proteolytic degradation of Factor V and Factor VIII. Protein S is, therefore, a physiological coagulation inhibitor.

If there is not a sufficient amount of S and C proteins or these do not function adequately, clots can form uncontrollably. The consequences of this phenomenon can be mild or very serious.

Because it is measured

The activity of protein S or its quantity can be deficient for various reasons. The decrease in the levels or the altered functionality of this parameter leads to a lower proteolytic degradation of factor V and coagulation factor VIII.

Therefore, its dosage is carried out for:

  • Establish the causes of one inappropriate formation of a thrombus (thrombotic event or venous thromboembolism);
  • Diagnose disorders that cause aexcessive clotting;
  • Detect hereditary or acquired deficiencies of the same or of protein C, with which it cooperates in the coagulation process.

To evaluate protein S, two types of tests are available:

  • Functional examination: measures the activity of protein S, focusing on the ability to regulate and decrease the formation of clots. The decrease in activity may be due to a reduced amount of the parameter or to the presence of non-functional forms.
  • Immunological analysis: establishes the amount of protein S present in the blood sample taken from the patient (note: the amount of free, bound or total protein S can be measured with this test).

This information can be useful in determining the type and severity of S protein deficiency.

When is the exam prescribed?

The examination of the coagulation protein S allows to measure its quantity and evaluate its functionality.

This analysis is generally indicated after an unexplained thrombotic event, as an aid to the diagnosis of hypercoagulation disorders, especially in young subjects (less than 50 years of age) and / or who have no other obvious reasons for manifesting this phenomenon.

Protein S testing may also be required in the case of multiple miscarriages. Furthermore, it is very important to check the values ​​of this protein before taking oral contraceptives; in women at risk, estrogen and progestogen drugs could cause venous thrombosis or other cardiovascular disorders.

Evaluation may also be advised when a patient has a close family suffering from a hereditary protein S deficiency.

Related exams

In conjunction with the protein S test, the doctor may also indicate that the following tests are performed:

  • Coagulative Protein C;
  • Antitrombina III;
  • Mutation of coagulation factor V;
  • Mutation of coagulation factor II;
  • Omocisteina.

Normal values

As regards the immunoassay, normal blood protein S values ​​are in the range of 15-30 mg / L (210-420 nmol / L).

L'functional examination (protein S activity with respect to a reference interval) is equal to:

  • S protein values ​​- women: 53 - 109% (in functional units: 0.53 - 1.09 U / ml);
  • S protein values ​​- men: 64 - 129% (in functional units: 0.64 - 1.29 U / ml).

Note: the reference range of the exam can change according to age, gender and instrumentation used in the analysis laboratory. For this reason, it is preferable to consult the ranges reported directly on the report. It should also be remembered that the results of the analyzes must be evaluated as a whole by the general practitioner who knows the patient's medical history.

Proteina S Alta – Cause

High levels of protein S are not usually associated with medical problems and / or pathological consequences, therefore they are not considered clinically relevant.

An increase in protein S can be observed in the case of:

  • Taking androgenic drugs;
  • Diabetes;
  • Sindrome nefritica.

Protein S Bassa - Cause

Protein S deficiency or lack of activity may be due to:

  • Acquired pathologies, such as liver or kidney disease, severe infections and cancers;
  • Hereditary alterations (passed on from parents to children).

Congenital or acquired protein S deficiencies result in ahypercoagulability (or one prothrombotic state).

Protein S: acquired defects

Acquired protein S deficiency may be due to:

  • Reduced synthesis;
  • Consumption increase;
  • Loss or passage of protein S from free to bound form.

The acquired protein S defect can be associated with:

  • Liver diseases (cirrhosis, liver failure, chronic hepatitis, etc.);
  • Excessive consumption (as in disseminated intravascular coagulation);
  • Vitamin K deficiency (reduced or missed dietary intake, therapies with dicumarolics or antibiotics that interfere with the synthesis of this vitamin, etc.);
  • Post-operative states;
  • Therapy with coumarin anticoagulants;
  • Severe or chronic infections;
  • Acquired Immunodeficiency Syndrome (AIDS);
  • Pregnancy;
  • Taking oral contraceptives;
  • Acute syndromes characterized by suffering of the respiratory system;
  • Inflammatory bowel disease;
  • Kidney disease (nephrotic syndrome, renal dysfunction;
  • Systemic lupus erythematosus;
  • Diabetes;
  • Heart attack;
  • Oncological diseases.

Often, in these acquired forms, the other natural anticoagulants, such as antithrombin III, are also decreased.

Protein S: congenital deficiencies

Congenital deficiencies of protein S can be caused by:

  • Reduced synthesis;
  • Synthesis of proteins with reduced biological activity (dysfunctional) for:
    • Reduced ability to bind to protein C.;
    • Reduced degradation capacity of factors V and VIII.

Hereditary protein S deficiencies are classified into three types:

  • Type I deficiency: there is a decrease in free protein S levels, while the total protein S is normal or slightly reduced (quantitative defect);
  • Type II deficiency: functional activity of the protein decreases, but the free protein S values ​​and total protein S levels are normal (qualitative defect).
  • Type III deficiency: it is a quantitative deficiency, in which there is a decrease in the levels of free protein S and normal levels of total protein S (quantitative defect).

Low protein S: possible consequences

Protein S deficiency is generally associated with a increased risk of thromboembolic events.

An S protein deficiency results, in fact, in a reduction of the anticoagulant activity of the blood (or in a state of trombofilia); as a result, the risk of abnormal blood clots (so-called thrombus).

These "lump" like formations can:

  • Go towards spontaneous dissolution;
  • Grow to the point of obstructing the vessel in which they originate;
  • Break, migrating into a circle and sometimes ending up occluding a smaller vessel.

The most fearful consequences of this condition, said thrombosis, are heart attack, stroke and pulmonary embolism. Protein S deficiency is the underlying cause of a small percentage of cases of disseminated intravascular coagulation (DIC) and deep vein thrombosis (DVT).

How it is measured

Protein S examination is performed on a blood sample venous taken from the arm.

Exam preparation

  • Before sampling, it is necessary to observe a fast of at least 8 hours, during which the intake of a modest amount of water is allowed.
  • In the two weeks preceding the analysis, oral warfarin (Cumadin®) therapy should be discontinued.
  • Before undergoing the examination, the patient must wait 10 days from a possible thrombotic phenomenon.

Interpretation of Results

The protein S assay is a test used to aid in the diagnosis of hypercoagulation disorders or to investigate the causes of venous thrombosis or thromboembolism.

Normal values ​​of protein S

Normal protein S activity and amounts indicate good coagulation regulation.

High protein S values

High levels of protein S are not usually associated with medical problems and are therefore not considered clinically relevant.

Low protein S values

The acquired protein S deficiency is mostly due to impaired hepatic synthesis. Low values ​​for increased protein S consumption are characteristic of disseminated intravascular coagulation and the postoperative period.

A low protein S value predisposes to excessive and inappropriate clot formation. If the protein is not functional, the coagulation process does not function sufficiently or adequately.

This can lead to an increased likelihood of developing a clot that obstructs blood flow in the veins (venous thromboembolism, VTE), but the extent of the risk depends on how bad or deficient the protein is.

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