What is a prothrombin mutation?
Prothrombin mutation, also called F2 G20210A or Factor II genotype, is an inherited genetic variant in the F2 gene. The F2 gene contains instructions for the formation of prothrombin, also called coagulation factor II, which is a central protein in the blood coagulation system.
In the prothrombin mutation, the nucleotide guanine (G) has been replaced by adenine (A) at position 20210 in the F2 gene. The variant affects the regulation of prothrombin and is often associated with higher levels of prothrombin in the blood. This can increase the blood's tendency to clot and thus the risk of venous thrombosis.
The function of prothrombin in the coagulation system
Prothrombin is formed in the liver and circulates in the blood as an inactive coagulation protein. When the coagulation system is activated, prothrombin is converted to thrombin. Thrombin, in turn, converts fibrinogen to fibrin, which forms a stabilizing network in the blood clot.
Coagulation is a vital process that limits bleeding in the event of injury. However, if the activity of the coagulation system becomes too high, it can contribute to the formation of blood clots inside the blood vessels without the need to stop bleeding.
Analysis of the B-F2 genotype
The B-F2 genotype is a genetic analysis that identifies the nucleotide variant 20210 G to A in the prothrombin gene. The analysis is performed on DNA extracted from blood.
Because the analysis examines the genetic material, the result is not affected by temporary changes in prothrombin levels or by treatment with anticoagulant drugs. The genotype is innate and does not normally change during life.
Interpretation of test results
The result is reported as genotype G/G, G/A or A/A:
- Genotype G/G is normal and means that the analyzed genetic variant has not been detected.
- Genotype G/A means that the A variant has been detected in one of the gene copies. This is called heterozygous prothrombin mutation and is associated with an increased risk of venous thrombosis.
- Genotype A/A means that the A variant has been detected in both gene copies. This is called homozygous prothrombin mutation and is associated with a higher risk of venous thrombosis than heterozygous genotype.
A deviant genotype means an increased risk, but is not the same as a person having an ongoing blood clot or definitely developing thrombosis. The result needs to be assessed together with medical history, heredity and other risk factors.
Hereditary and incidence
The prothrombin mutation is hereditary. A person with a heterozygous genotype has the variant in one of their two gene copies and can pass it on to biological children. Homozygous genotype means that the variant has been inherited from both parents.
Heterozygous prothrombin mutation occurs in about two percent of the population, but the incidence varies between different geographical and ethnic populations.
What conditions may be related to prothrombin mutation?
Prothrombin mutation is primarily associated with an increased tendency to develop venous thromboembolism. Conditions that may be related to the variant include:
- deep vein thrombosis, which involves a blood clot in a deep vein, usually in the leg.
- pulmonary embolism, which occurs when a blood clot travels with the blood flow to the lungs.
- recurrent venous blood clots
- venous thrombosis in unusual vascular areas.
Prothrombin mutation is mainly a risk factor for venous thrombosis. The association with arterial blood clots, such as myocardial infarction and ischemic stroke, is less clear and is generally of less clinical importance.
Other factors affecting the risk of thrombosis
The individual risk of thrombosis is influenced by the combination of genetic and acquired factors. The risk may be further increased in the case of, for example:
- previous venous thrombosis.
- Factor V Leiden or other hereditary thrombophilia.
- antithrombin, protein C or protein S deficiency.
- pregnancy and the period after childbirth.
- estrogen-containing contraceptives or hormone therapy.
- major surgery or prolonged immobilization.
- cancer.
- old age and obesity.
A combination of a prothrombin mutation and other thrombosis risk factors can mean a significantly higher risk than the genetic variant alone.
Analysis method
The analysis is performed with probe-based real-time PCR regarding nucleotide 20210 in the prothrombin gene, also called the Factor II gene. The analysis is performed on DNA that has been extracted from blood.
Medical assessment in case of abnormal test results
A proven predisposition needs to be assessed based on the person's overall risk profile. Consideration is given to previous blood clots, family history, other genetic or acquired risk factors, and situations such as pregnancy, surgery, and hormone therapy.
A prothrombin mutation does not automatically mean that preventive treatment with blood-thinning drugs is necessary. The need for medical follow-up and any preventive measures is determined individually by the doctor.
