Causes

Among the diseases associated with reduced coagulation, there are diseases caused by a malfunction of the blood platelets (thrombocytes). Functioning blood platelets form the basis of the first part of the clotting of the blood, and by attaching the cells the bleeding is restricted. In the case of platelet disease, there may be a malfunction or deficiency of the platelets.

In most cases this is a deficiency, which can be congenital or autoimmune, for example. Special drugs can also trigger it. Typical for the presence of a platelet coagulation disorder is the occurrence of small punctiform skin and mucous membrane bleedings (petechiae).

In addition to a lack of platelets, a lack of coagulation factors is also known to trigger a coagulation disorder. This can be a congenital or acquired form. A lack of coagulation factors usually results in an increased incidence of bruising and even bleeding into the muscles.

Since the liver is responsible for the production of coagulation factors, liver diseases can also lead to a lack of coagulation factors. Since vitamin K is also needed by the liver to produce certain clotting factors, a lack of vitamin K, for example due to a reduced dietary intake of vitamin K, also leads to an increased bleeding tendency. The effect of vitamin K can also be neutralised by medication or disease.

The two haemophilia diseases (haemophilia A and B), which lack factor 8 (XIII) and factor 9 (IX) respectively, are generally known to be congenital factor deficiencies. Compared to other coagulation disorders, however, this is a rare disease. Haemophilia A is much more common than haemophilia B.

Both forms of haemophilia are associated with a high risk of bleeding, so patients must adapt their lifestyle to the disease in order to avoid life-threatening situations. Often the missing coagulation factor must also be replaced (substituted). Due to the nature of inheritance (X-linked recessive), it is mainly boys who suffer from this disease.

Girls/women only rarely contract the disease, but they are often carriers (so-called carriers) of the disease. The most common congenital coagulation disorder, which occurs in about one percent of the population, is von Willebrand syndrome. This disease does not lack a coagulation factor, but the von Willebrand factor, which is important for the aggregation of blood platelets.

In contrast to haemophilia patients (hemophilia), those affected are less restricted in their lifestyle. There are many acquired causes for excessive coagulation (thrombophilia), which leads to clot formation. These are causes that can usually be changed by changing one’s lifestyle.

The risk factors for increased clotting include the use of hormonal contraceptives, pregnancy, long immobilization, for example by being bedridden or travelling long distances, high nicotine consumption and overweight. If risk factors are present and thrombosis has already occurred, thrombosis prophylaxis, such as Marcumar, is often prescribed. Genetic diseases can also trigger an increased tendency to thrombosis.

These diseases include factor V Leiden mutation, antithrombin deficiency, and protein C and protein S deficiency. Coagulation factor 5 (V) promotes the formation of thrombin. Thrombin in turn is important for the formation of the fibrin scaffold, which stabilises the blood platelets that attach themselves to the wound in the vessel wall.

Its active form is inhibited by protein C. If a mutation in the factor 5 gene occurs, the disease “factor 5 suffering” develops. This is a hereditary disease which is inherited in a dominant mode of inheritance. (Incidentally, the word “suffering” in the name of the disease does not come from the verb “to suffer”, but from the Dutch city of Leiden, where the disease was discovered) The mutation causes a minimal change in the structure of coagulation factor 5 (V) so that its antagonist, protein C, which normally binds to factor 5 (V) and inhibits excessive coagulation, can no longer interact properly with factor 5.

As a result, the blood clumps (coagulates) more easily, increasing the risk of thrombosis. The thromboses usually develop in venous vessels, which transport the oxygen-poor blood back to the heart. The severity of the disease depends on whether the diseased gene was transmitted by both parents and is therefore a so-called homozygous carrier or only by one parent (so-called heterozygous carrier).

If one is only a heterozygous carrier, the risk of thrombosis is about 10% higher, while homozygous carriers have a 50-100 times higher risk. How is the disease diagnosed? Patients usually become conspicuous by the fact that they have an above-average incidence of thrombosis.

Thromboses also occur at a younger age. In these cases, a Factor V Leiden mutation should always be ruled out by a haematologist (doctor who deals with blood). Furthermore, other members of the family are usually also ill, so that in this case early clarification is advisable.

The mutation is detected by determining the clotting time. Normally, clotting should be inhibited by adding activated protein C. This is not the case with factor V Leiden. If this test is positive, a genetic test is performed.

In principle, permanent drug therapy is not necessary. Thrombosis prophylaxis is only prescribed in the case of thrombosis or if the risk of thrombosis is further increased by other circumstances, such as a long-haul flight. Protein S is an important factor in the coagulation system.

Within the coagulation cascade, it acts as a cofactor and activates the protein C. Together the two proteins form a complex that inactivates the activated coagulation factors V and VIII. As a result, less fibrin is produced. The coagulation is thus weakened.

If protein S is missing due to a genetic defect or too little is produced in the liver, this affects the entire coagulation system. Since protein S is produced in a vitamin K-dependent way, a deficiency can occur due to too little vitamin K. Liver diseases such as inflammation or chronic malfunction can lead to this. Other genetically determined types of disease are also possible.

For example, total protein S may be within normal limits, but may not function properly. Due to the lack of protein-S, protein C is not activated and it cannot inactivate factors V and VIII. Logically, the clotting process is then intensified, making the blood more prone to develop clots.

Because of the increased tendency of patients to form blood clots, they must take blood-thinning medication for prevention, depending on their age and situation. The coagulation factor 7 (VII) is also known as proconvertin and plays an important role in the coagulation cascade. A deficiency of factor 7 (VII) is called hypoproconvertinemia.

The disease is characterised by an increased tendency to bleed, with symptoms similar to those of haemophilia. A deficiency of factor 7 (VII) can, but need not necessarily, be inherited. The mode of inheritance of factor 7 (VII) deficiency is recessive, which means that a defective gene must be inherited from each parent for the disease to break out. Since Factor 7 (VII) is one of the coagulation factors that are produced by the liver as a function of vitamin K, a vitamin K deficiency can also lead to a deficiency of Factor 7 (VII). During surgery, the activity of this factor can be increased, resulting in increased clotting.