Thrombophilic mutations

Thrombophilia is a tendency to increased blood coagulation which is influenced both by congenital predispositions and external factors (sports, weight, age, smoking, accidents or medications). People with higher blood clotting are more prone to blood clots (thrombi), which can lead to partial or complete closure of the blood vessels - mostly of deep veins of the legs (deep vein thrombosis). Parts of the clot can come loose, travel through blood vessels and after passing through the heart close any of the pulmonary arteries - then pulmonary embolism arises. Thrombosis of the placenta can endanger the course of pregnancy.

The external stimulus to formation of blood clots may be hormonal contraceptives and hormone treatment for infertility or during pregnancy. Therefore, examination of congenital hereditary component of thrombophilia belongs to basic preconception genetic testing. Examination results affect infertility treatment and care for pregnant women. Knowledge of innate disposition to blood clotting may help not only in reproductive age, but also in operations, prolonged immobilization or treatment of chronic diseases.

We investigate two significant changes - thrombophilic mutation of genes F5 and F2, which influence the structure and function of two proteins (factor V and factor II). Both of them are substantially involved in the clotting process:

Leiden mutation (FV Leiden) of gene for coagulation factor V - mutation on position number 1691 in gene F5 leads to substitution of amino acid arginine for glutamine at position 506 (R506Q) of this protein
Mutation of gene for coagulation factor II (F II prothrombin) - mutation at position number 20210 of gene F2

Findings of mutation mean increased innate predisposition for blood clotting. It is therefore necessary to introduce certain preventive measures. There are 5 – 10% carriers of mutation FV Leiden and 1 – 2% carriers of mutation FII prothrombin in the Czech population.

How is thrombophilia inherited?

Thrombophilic mutations are transmitted from one generation to another.

We distinguish two types:

heterozygote – individuals who inherited the mutation only from one parent. Their liver produces a mixture of normal factor and active clotting factor or its increased amount. The result is increased risk of developing thrombosis.
homozygote - individuals who inherited the same mutation from both parents. Their liver produces only the active factor with a more significant outcome. The risk of developing thrombosis is therefore very high.

It is an autosomal dominant inheritance, heterozygotes (carriers of a single mutation) have a 50% risk of passing the mutation to their children regardless of their gender, homozygotes pass the mutation to their children at all times.

What is the risk of developing thrombosis?

Presence of congenital thrombophilic mutation presents 3-5x higher risk of developing deep vein thrombosis in comparison with normal population. This does not necessarily mean that each carrier will suffer from thrombosis. Its development occurs mainly only after interaction of other acquired thrombophilia factors:

age over 45 years
obesity, smoking, alcohol
atherosclerosis and other cardiovascular diseases
abdominal and orthopedic operations
accidents and long-term immobilization
hormonal contraception or sex hormone treatment (it is contraindication in homozygote of thrombophilic mutation)
pregnancy and postpartum
oncological diseases and their treatment
loss or insufficient intake of fluids (dehydration)
autoimmune diseases (for example, antiphospholipid antibodies)
presence of mutations of other genes associated with blood clotting

When various thrombophilic factors are present, it may result in thrombosis in anyone, but in individuals with congenital thrombophilia only minor external influence is sufficient to induce thrombosis.

What is the prevention of the development of thrombosis?

The key element to prevent and minimize the problems associated with the formation of thrombosis is the knowledge of genetic predispositions. Diet and lifestyle may be modified on the basis of the information - enough exercise, balanced diet with adequate fluid intake, maintaining optimal body weight and no smoking. The risk of disease can be significantly reduced due to such basic preventive measures. Hematological monitoring or possibly therapy in high risk situations - such as during pregnancy - is provided at the same time.

Before necessary medical interventions always tell your doctor about your tendency to increased blood clotting!