Thrombosis: Diagnostics, Gene Mutations

Only the congenital risk factors of thrombophilia, which are very common, are presented below:

Factor V Leiden Mutation (APC Resistance)

Factor V is a component in what is called the coagulation cascade of the blood, that is, in the process of blood clotting.A mutation of the gene for factor V results in what is called APC resistance. This mutation causes increased hemostasis (blood clotting) and thus increases the risk of thrombosis.

When factor V is activated, it ensures that the process for blood clotting takes place. Activated protein C (APC) is required to stop blood clotting. APC binds to a specific site of factor V and cleaves it. In the factor V Leiden mutation, however, there is a defect in the gene exactly at the site where APC normally binds and stops blood clotting.

The APC cannot bind to factor V, resulting in increased blood clotting.

The factor V Leiden mutation occurs in about 5% of the population in Europe.If this mutation is inherited from only one parent (heterozygous), the risk of thrombosis increases 5 to 10 times compared with people without the mutation.However, if the mutation is inherited from both parents (homozygous), the risk of thrombosis is 50-100 times higher than in people without a hereditary predisposition to thrombosis.

Factor II mutation (prothrombin mutation G20210A)

Prothrombin is a component of blood clotting. It is formed in the liver and converted by an activator into thrombin, which is relevant for blood clotting. Thrombin ensures that the blood platelets (thrombocytes) are released and can form a wound closure (platelet aggregation).Furthermore, thrombin converts fibrinogen into fibrin, which is a component of blood clots.

In the case of a mutation of the genes that regulate factor II (prothrombin mutation G20210A), there is too much prothrombin in the blood.About 2% of the population are affected by such a mutation. This increases the risk of thrombosis by a factor of about 3.

Pregnant women with a factor II mutation even have a 15-fold increased risk of thrombosis.

Hyperhomocysteinemia

Hyperhomocysteinemia (see homocysteine) – elevated levels likely promote thrombosis predisposition:Genetic cause: autosomal recessive inheritance; point mutation; enzyme activity is reduced by circa 70% in affected individuals:

  • “Wild type” – healthy: circa 40 %.
  • Heterozygous trait carrier: 45-47 % (homocysteine levels of 13.8 ± 1.0 μmol/l)
  • Homozygous trait carrier: 12-15 % (homocysteine levels of 22.4 ± 2.9 μmol/l)