Thrombophilia

Thrombophilia is an increased tendency for blood clots to form in the blood vessels, i.e. in the arteries and veins. These clots are also known as thromboses. Thrombophilia can have genetic causes, i.e. congenital or acquired. The most frequent are presented in the following text.

Epidemiology

In Europe and America, about 160 people per 100,000 inhabitants per year suffer from thrombosis in the veins. The risk rises sharply with increasing age.

Causes

As already mentioned, thrombophilia can be caused by genetic factors, i.e. congenital and/or acquired factors. The most important ones are presented below. APC – Resistance/Factor V -(five)- Leiden- Mutation Coagulation factor V (i.e. five) is an important component of our coagulation system.

To be more precise, it is part of a so-called coagulation cascade, which ultimately leads to the blood platelets, the so-called thrombocytes, clumping together firmly and thus closing 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, can be inactivated, i.e.

broken down, since otherwise blood clots, i.e. thromboses, can form at unintended locations. This is known as thrombophilia. The so-called activated protein C (APC) is responsible for the inactivation of coagulation factor V. In the case of APC resistance, coagulation factor V is mutated; this is known as a factor V Leiden mutation.

As a result of this mutation, Factor V is resistant, i.e. resistant to the activated protein C and cannot be inactivated, with corresponding consequences. Especially in younger patients between 20-40 years of age, APC resistance is found to be the cause of up to 30% of thromboses. The risk of thrombosis in women with an existing mutation increases dramatically when taking oral contraceptives, such as the pill (see: Risk of thrombosis with the pill).

Protein C and Protein S deficiency Protein C and S are the body’s own inhibitors of blood clotting. They break down and inactivate certain coagulation factors (factor V/five and factor VIII/eight) and thus prevent excessive thrombus/clot formation. Protein C is the cleaving enzyme and Protein S the auxiliary enzyme.

A deficiency of either of these enzymes leads to increased blood coagulability with subsequent increased formation of blood clots, i.e. thrombophilia. The deficiencies can be congenital or acquired. A congenital, inherited deficiency is very rare.

The symptoms become apparent very early, sometimes in the first days of life. An acquired deficiency can have various causes. The two most important are liver diseases, since all clotting factors, but also protein C and S are produced in the liver, and increased consumption in the context of so-called bacterial sepsis, i.e. blood poisoning caused by bacteria in the bloodstream.

Antithrombin deficiency Like protein C and S, antithrombin is a blood clotting inhibitor produced in the liver. It inactivates various clotting factors and thus inhibits clotting and thus the formation of thromboses. Heparin enhances the effect of antithrombin by a factor of 1000, thus accelerating the inactivation process.

In this way, heparin unfolds its anticoagulant properties. Prothrombin mutation Prothrombin is the precursor of so-called thrombin. Thrombin is also a coagulation factor but also plays an important key role in the entire coagulation process, as it is able to additionally activate the other coagulation factors and thus enhance coagulation and subsequent clot formation.

If there is a prothrombin mutation, more prothrombin is produced than the body actually needs. This leads to an increased amount of thrombin with the consequence of increased blood coagulability and uninhibited thrombosis formation. After APC resistance, the prothrombin mutation is the second most common cause of a congenital, i.e. inherited, tendency to thrombosis (thrombophilia).

Antiphospholipid antibodies If our body forms antibodies, i.e. defense substances, against healthy structures of our body instead of, for example, against disease-causing bacteria or viruses, we speak of an autoimmune disease. The body virtually attacks itself.Antiphospholipid antibodies are also autoimmune antibodies. They are directed against so-called endogenous phospholipids.

Phospholipids are fats that play an important role in our body for coagulation, among other things. If the antibodies attack these structures, this leads to clumping of the coagulation platelets (thrombocytes) and subsequently to thromboses and embolisms. Often, these antibodies can be found in the context of other autoimmune diseases, such as so-called collagenoses, here especially in the case of butterfly lichen (lupus erythematosus) and rheumatic diseases in the body.

These antibodies can also be produced in connection with malignant tumor diseases and infections. Heparin-induced thrombocytopenia Paradoxically, after administration of heparin, this disease initially leads to excessive platelet aggregation with subsequent blockage, especially of small arteries and capillaries. Heparin forms a complex with a coagulation messenger substance.

This leads to the formation of autoimmune antibodies, which adhere to this complex and subsequently cause the platelets to clump together. The massive consumption of platelets subsequently leads to a sharp drop, which in turn can result in an increased tendency to bleed and pose a great danger. This disease occurs mainly during high-dose heparin treatments that last longer than 5 days.

Idiopathic Meanwhile, in 60% of cases one of the above mentioned causes can be found as the reason for the increased tendency to clot. However, this also means that in 40% of the cases no clear cause for the complaints can be found. This is then referred to as idiopathic thrombophilia.