Internal Medicine

Thrombophilia

definition

A thrombophilia is one increased tendency to form blood clots in the blood vessels, i.e. in the arteries and veins.
These clots are also technically called Thrombosis known. The thrombophilia can be genetic, that is innate or acquired causes underlie.

The most common are presented in the following text.

Epidemiology

In Europe and America About 160 people per 100,000 inhabitants suffer one per year thrombosis in the veins.

The risk increases sharply with age.

causes

As mentioned earlier, thrombophilia can genetic, so innate and / or acquired factors own as a cause. The most important ones are presented below.

APC resistance / factor V (five) Leiden mutation

Coagulation factor V (read five) is an important part of ours Coagulation system.
More precisely, it is part of a so-called Coagulation cascade, which ultimately causes platelets, called the Platelets clump tightly and thus close a possible wound quickly and stably.
However, it is not only important that the clot formation can proceed without complications. It is at least as important that the corresponding coagulation factors, including factor V, are inactivated reduced otherwise uninhibited and in unintended places Blood clot formation, so thrombosis can occur.
One then speaks of the disease thrombophilia. For the inactivation of coagulation factor V is the so-called activated protein C (APC) responsible. In the case of APC resistance, the coagulation factor V is mutated; one speaks of a factor V Leiden mutation.
This mutation makes factor V resistant, i.e. resistant to the activated protein C and can not inactivated with corresponding consequences. APC resistance for up to 30% of thromboses can be found as the cause, especially in younger patients between 20 and 40 years of age.
The risk of thrombosis increases immensely in women with an existing mutation when taking it oral anti-contraceptivessuch as the pill (see: Thrombosis risk of the pill).

Protein C and Protein S deficiency

Protein C and S are endogenous inhibitors blood clotting, i.e. clot formation.
They split and inactivate certain coagulation factors (factor V / five and factor VIII / eight) and thus prevent one excessive thrombus / clot formation.
Protein C here is that divisive, Protein S the Auxiliary enzyme. A deficiency in one of the two leads to an increased coagulability of the blood with subsequent increased formation of blood clots, i.e. thrombophilia.

The defects can be congenital or acquired.
A congenital, inherited deficiency is very rare. The symptoms appear very early, sometimes in the first days of life noticeable.
An acquired deficiency can have various causes. The two most important are on the one hand Liver disease, because all coagulation factors, but also protein C and S are produced in the liver and on the other hand an increased consumption in the context of a so-called bacterial sepsis, so one Blood poisoning caused by bacteria in the bloodstream.

Antithrombin deficiency

Antithrombin is like protein C and S one in the liver formed inhibitor of blood coagulation. It inactivates various coagulation factors and thus inhibits coagulation and thus the formation of thromboses. Heparin increases the effect of antithrombin by a factor of 1000, thus accelerating inactivation. Developed in this way Heparin his anticoagulant properties.

Prothrombin mutation

Prothrombin is that Prepress the so-called Thrombins. Thrombin is also a coagulation factor, but it also plays an important key role in the overall coagulation process, as it is capable of the other coagulation factors to be activated additionally and thus to increase coagulation and subsequently the formation of clots. If there is a prothrombin mutation, more prothrombin is produced than the body actually needs. This also leads to an increased attack of thrombin, with the result that the blood can coagulate and the formation of thrombosis is unchecked. The prothrombin mutation is after the APC resistance the second most common cause of a congenital, i.e. inherited tendency to thrombosis (thrombophilia).

Antiphospholipid antibodies

Forms our body antibody, i.e. antibodies, against healthy structures in our body instead of, for example, against pathogenic bacteria or viruses, that's what we call one Autoimmune disease. The body is basically attacking itself.
Even with the Antiphospholipid antibodies it is an autoimmune antibody. They are directed against so-called endogenous phospholipids. Phospholipids are Fatswhich, among other things, play an important role in our body's coagulation. If the antibodies attack these structures, this leads to Clumping of the coagulation platelets (Platelets) and then on thromboses and embolisms.
Often these antibodies can occur in the context of other autoimmune diseases, such as with so-called Collagenoses, can be found here especially in the case of lupus erythematosus and rheumatic diseases in the body. Also related to malignant tumor diseases and Infections the formation of these antibodies is possible.

Heparin-induced thrombocytopenia

With this disease it happens paradoxically after the gift of Heparin initially to excessive clumping of platelets with subsequent constipation, especially small arteries and capillaries. Heparin forms a complex with a coagulation messenger.
It comes to the creation of Autoimmune antibodiesthat adhere to this complex and subsequently lead to clumping of the platelets. Through the massive consumption of platelets there is subsequently a sharp drop, which in turn manifests itself in an increased tendency to bleed and can represent a great danger.
This disease occurs mainly high-dose heparin treatments that last longer than 5 days.

Idiopathic

Meanwhile can in 60% of the cases one of the above causes can be found to be the reason for the increased tendency to clot. But this also means that no clear cause in 40% of cases for the ailments can be found. One then speaks of idiopathic thrombophilia.

Symptoms

The symptoms of thrombophilia are very diverse and depend on the position of the vessel in the body, which is narrowed or blocked by the clot that has formed.

Usually a thrombophilia only falls during the examination of a existing thrombosis or embolism on.
Under one embolism one understands the constipation of a artery, for example in the lungs, the heart or the brain, usually through a blood clot with a subsequent inadequate supply of the tissue with oxygen and nutrients.
Furthermore, should also be Women with repeated Miscarriages Thrombophilia is considered and appropriate diagnostic measures are taken.
Thromboses, especially those in the deep veins of the leg, are expressed through Swelling, Skin discoloration, such as Pain in the affected leg.
There is clinical evidence of the presence of thrombophilia, such as a common and recurring propensity to Clot formation, especially at a young age, known family tendencies to thrombosis and the formation of clots unusual positions, for example in the vessels of the Brain, in the veins of the Intestines, of the spleen, of the liver and the Kidneys.

diagnosis

Often times, the suspicion of the presence of a Thrombophilia with frequent, recurring Thrombosis posed.

The appearance of blood clots before the 45 years of age, as well as the occurrence of already known Propensity to thrombosis in the family. Based on this suspicion, further diagnostic measures are based on which an attempt is made to find the cause of the thrombophilia.
In addition, examinations are carried out with the aim of finding out where blood clots could have already formed everywhere in order to be able to strive for the best possible therapy.

Whether and, if so, why there is increased coagulability of the blood (thrombophilia) can be determined with the help of certain Laboratory tests to be found out.
For this test, blood must be drawn from the person concerned. The tests include, among other things, the examination for the presence of a possible APC resistance, the close examination of the Factor V, as well as factor II (prothtrombin) for a possible mutation, as well as the determination of the activity and, if necessary, the amount of Protein C, Protein S, as well as those of Antithrombin in blood. (Explanation of APC resistance, factor V, factor II, protein C, protein S, antithrombin in the causes section).

Additionally will also antibody searched in the blood, which may be a reason for the increased tendency to clot.

Furthermore, the Clotting time of the blood and general Blood parameters certainly. It's important about that 3 to 4 weeks No anticoagulant drugs, such as for example, before the blood test Marcumar® or Heparin were taken as they can falsify the laboratory results.
However, the medication should not be discontinued independently, but always in consultation, ideally with the attending physician.

One already existing thrombosis in the veins of the leg, for example, can often already be determined by the assessment and the Comparison of the legs be determined in the course of an investigation. Often a Ultrasonic the leg veins, which can reveal a possible blood clot. Furthermore can computed tomography / CT examinations, especially to rule out embolisms.

therapy

The best therapy for known thrombophilia is this prophylaxis, i.e. to counteract the development of thrombosis.

This works best if you have the Risk factors knows about their development and accordingly, especially through health-conscious behavior, prevents.
Prevention is particularly important for people who have an inherent risk (see section "Causes") of developing thrombosis. There are also certain, so-called acquired risk factors present, or if the affected patients consciously expose themselves to these factors, which increase the development of dangerous blood clots even in healthy people, the probability of a thrombotic event increases sharply.
To this Risk factors counting:

Smoke
Obesity
height Cholesterol levels
Taking birth control pills
Taking hormones during menopause
low fluid intake
Varicose veins (varices)
Operations, especially major orthopedic surgery
Sedentary lifestyle in the hospital bed or during a trip, for example in the car, bus, plane,
acute infections
Tumor diseases
pregnancy/Puerperium.

Some risk factors can however be reduced and thus the development of thrombosis specifically counteracted become. This is achieved, for example, through the Give up cigarettes, a diet if you have one Obesity and avoiding long periods of sitting.
For long journeys, one should use adequate hydration, as well as sufficient Movement while driving or flying be respected. In the case of longer and frequent air trips, specially made Thrombosis stockings recommendable. A specific one, above all medical therapy depends on the current condition and previous illnesses of the person concerned, as well as on the reason for the thrombophilia, if one could be found.
Goal one drug therapy Is that it Blood less capable of clotting to make and thus counteract the development of thrombosis. Most often this succeeds in the case of thrombophilia with the so-called Marcumar® (Active ingredient phenprocoumon). Marcumar® is taken as a tablet. In the body it acts as a Antagonist to vitamin K. Vitamin K, in turn, is important for the regeneration of coagulation factors. As the coagulation factors consequently not regenerated and can be made operational again, the coagulability of the blood decreases. Long-term therapy with heparin can be used as an alternative drug. However, this is contraindicated in the presence of known heparin-induced thrombocytopenia (see section “Causes”).

Whether the anticoagulant therapy should be permanent or only for a certain period of time depends on the Cause of thrombophilia, Number, location and severity of previous thromboses and / or embolisms, as well as any upcoming, planned operations and / or an existing one pregnancy.

Permanent anticoagulant therapy should especially be given to a well-known Antiphospholipid syndrome, at the Antithrombin deficiency, as well as recurring, spontaneous vascular occlusions due to blood clots.

Women should stop taking the birth control pills dispense. If a blood thinning therapy, for example with Marcumar®, is carried out, however, the patient has the option of continuing to take the contraceptive pill in consultation with her doctor.

forecast

Lies a Genetic defect, such as the factor V Leiden mutation underlying thrombophilia, this cannot be avoided causal to treat.
By early detection of the disease and subsequent prophylactic measures, such as lifestyle adjustments (sport, abstinence from nicotine, healthy diet, etc.) and anticoagulant drug therapy can help Risk of thrombosis however significantly reduced become

Further information

Further information on the subject of thrombophilia / thrombosis can be found at: