Protein S deficiency

definition

At the Protein S deficiency is it a congenital disease of the body's blood clotting systemwhich is caused by a lack of the anticoagulant protein S. This disease has a prevalence of around 0.7 to 2.3% in the normal population kinda rare.

Protein S is usually formed in the liver and, together with other anticoagulant factors, ensures that a Blood clot remains limited to the location of the vascular injury.

If this protein is deficient, the factors responsible for the formation of blood clots predominate, so that the clinical picture, for example, with a increased tendency to form clots within intact blood vessels.

Patients are at an increased risk of having a Leg vein thrombosis or one caused by a clot acute closure of any blood vessel.

This clot (thrombus) can also close vital vessels so that a Deficiency / undersupply of dependent organs can lead to tissue destruction, for example in the heart, lungs, brain or intestines.

Are there different forms of the disease?

In principle, the patient's clinical picture is independent of the presence of the various sub-forms. However, one speaks of three subtypes, which distinguish diagnostically to let:

• Type I: It is characteristic of type I that the activity of the protein S present is reduced; but also the concentration of the total protein, as well as the free (active) protein in the blood is reduced. By definition, type I is present when the amount of free protein falls below 40% of the normal value.

• Type II: A type II deficiency is present if only the activity of protein S is reduced, but the concentrations of both the total and the free protein are unchanged.

• Type III: Assign the patient a normal concentration of total protein S on, but with a decreased concentration of free protein (<40%) and one Malfunction associated with this, they suffer from type III protein S deficiency.

General clotting

The blood clotting divides into the cellular portion, which is achieved through the aggregation, networking and activation of Platelets (Platelets) is embossed, as well as the plasmatic partduring which blood components form a kind of network in which circulating red blood cells (Erythrocytes) and stabilize the clot.

In healthy people, a blood clot forms only after a vessel is injured; fibers (consisting of Collagen), which outside the vessel located, exposed, to the Accumulate platelets and thus induce an initial, unstable closure of the wound.

This attachment (adhesion) solves the Platelet activation from which to Release of various substances, how Calcium and thromboxane leads. Thromboxane supports the closure of the wound by providing a local vasoconstriction; Calcium, on the other hand, is essential for the function of various factors in the plasmatic coagulation phase.

As part of their activation the platelets also change their structure, so that the surface of the platelets increases and their aggregation has a somewhat higher stability.

The ultimate stability of the clot is only secured within the scope of the plasmatic component, whereby as a result of the activation of the so-called coagulation cascade (consisting of various Vitamin K-dependent factors) Red blood cell storage and the Cross-linking of platelets among each other, the thrombus is stabilized until the original wound is finally closed. In the context of wound healing this is Blood clots increasingly broken downso that ultimately the defect through new vascular tissue is closed.

If there is no injury, it can nevertheless to induce blood clotting come what the body is effective prevent with the help of an opposing system can; there is a constant balance between clot formation and breakdown, which is strictly controlled.

The formation of a clot is inhibited by various factors that reduce the effectiveness of the thrombus formation and thus prevent the formation of a clot within an uninjured blood vessel.

These factors include a complex consisting of Protein S and Protein C, which together form a inhibitory effect on the stabilization of the primary blood clot Exercise in the plasmatic phase of blood clotting.

It should be noted that protein C is basically present in its active form and thus the inhibitory activity of the two proteins only from activation and aggregation with protein S. depends.

If a patient suffers from a deficiency of protein S, this is Inhibitory effect of protein S and protein C decreased or can theoretically be omitted completely, so that the risk of the formation of a thrombus is increased in the absence of a vascular injury.

Read more about the topic here: Blood clotting

Symptoms

Most of the time, the patients fail early appearance of venous blood clots between the ages of 15 and 45 on.
Women in particular suffer unexpectedly and without first knowing about their disease thrombosis (Vascular occlusion by a blood clot), accumulated in the deep leg veins.

This mostly occurs in Risk situations including while taking Estrogens (Birth control pills, Hormone preparations for menopausal symptoms) or pregnancy as these are also associated with a decrease in protein S concentration.

Further Risk factors Suffering from deep vein thrombosis that affects both sexes equally include:

• Operations,
• prolonged immobilization / immobilization of the legs after an operation or during a long flight / bus trip,
• such as increased fluid loss.

diagnosis

The disease can only be detected by analyzing the patient's blood. If a patient is suspected of having an increased tendency to clot, a venous blood sample is usually taken and then a laboratory analysis of the activity of the anticoagulant factors in the blood, such as protein S.

It should be noted, among other things, that protein S and the other factors only have a short half-life, i.e. their activity can only be detected within a relatively short time window, so that it is important to avoid long transport routes to a laboratory. It is therefore recommended to have these examinations carried out by a specialist with an attached laboratory or in a hospital.

Furthermore, the synthesis of protein S and protein C is also vitamin K-dependent, so that medication with vitamin K antagonists (antagonists) such as Marcumar, for example, can lead to incorrectly low values.

It should also be borne in mind that the concentration of protein S in women is generally around twenty percent lower than in men of the same age and in connection with increased estrogen levels (for example when taking the birth control pill or hormone preparations during menopause), as well as during and may also be decreased shortly after pregnancy.

Therefore, a minimum interval of eight weeks after the last intake of the vitamin K antagonist and the end of the influence of estrogen is recommended.

therapy

The disease is based on one inherited genetic defectwhich makes treatment difficult as it is not possible to treat the underlying cause.

The treatment is therefore mainly based on the patient's condition, whereby asymptomatic suffererswho have not yet suffered a thrombosis no permanent medication need. However, in the event of a risk situation described above, you are advised to inform your treating physician about the presence of the disease so that an adequate supply of anticoagulant medication, such as Heparin, can be done.

Usually the patients stay inconspicuous for years and the disease will only after the occurrence of a first thrombosis diagnosed.

However, this means that therapy with an anticoagulant drug should be advised to prevent new clots from forming.

Since vitamin K is required for the synthesis of important coagulation factors, the use of is recommended for longer-term treatment Vitamin K antagonists (antagonist = Opponent), such as Marcumar, on. These displace vitamin K from the synthesis of the factors required for plasmatic coagulation, so that the lack of inhibitory effect of protein S and C is no longer "significant".

If you have a known protein S deficiency in pregnant women becomes a closer observation and if necessary, treatment with anticoagulant drugs, recommended during pregnancy to reduce the risk of thrombosis and associated Pregnancy complications to avoid.

How is the disease inherited?

Since the disease is not inherited linked to the sex chromosomes Affected women and men equally.

Furthermore, one speaks of a dominant inheritance, since a change in only one of the two responsible genes leads to the expression of the deficiency.

The probability As a result, having the genetic trait of protein S deficiency also amounts to for first-degree blood relatives Affected (Parents, children, siblings) 50 percent. However, since the deficiency does not automatically go hand in hand with the development of a thrombosis, many patients only recognized after decades.

Is the presence of one Known for lack within the family, can a Examination of first degree relatives, especially female family members of childbearing age or before therapy with estrogens (female sex hormones) can be useful. An examination is usually without problems from the sixth month of life possible, although "screening examinations" are generally refrained from if there is a known case within the family.

Prophylaxis for those affected

Compared to other clinical pictures, no positive influence on the anticoagulant has so far been detectable in the context of a special diet.

However, doctors recommend in the presence of very overweight a Change of diet on a wholesome, vitamin-rich, possibly Mediterranean-inspired diet with the goal of a general weight loss. This basically has a positive effect on the cardiovascular system, but has no specific preventive benefit in the context of a protein S deficiency.

To one thrombosis is to be prevented regular exercise as well as that Wearing support / compression stockings especially in risky situationshow typically one long flight / bus trip, highly recommended.

Does the person concerned already suffered a thrombosis, this should be strictly follow the instructions of your doctor, and conscientiously take prescribed medications to prevent recurrence. To prevent the occurrence of a common complication of a previous thrombosis (the so-called PEastern Thrombotic Syndrome) to counteract, the patient should wear compression stockings daily.