Blood coagulation, factor V Leiden and 20210G-A

Thrombophilias are hereditary and/or acquired pathologies that predispose to blood clots or thrombosis. Among the genetic factors identified, the Factor V Leiden mutation and the prothrombin gene 20210G-A mutation are the most studied.

The term hereditary thrombophilia has generally been applied to pathologies in which a genetic mutation affects the amount or function of a protein of the coagulation system. The most studied mutations are factor V Leiden or rs6025 and the prothrombin gene 20210A-G or PGM.

Hypercoagulability or thrombophilias are multifactorial conditions that may have a different etiology. In addition to the possible genetic contribution, several factors must be taken into account to properly assess the individual risk of thrombophilia. Acquired thrombophilia may be due to specific diseases such as, for example, myeloproliferative neoplasms and deficiencies in natural coagulants. Some drug treatments (oral contraceptives, hormonal treatments and chemotherapy) and other factors such as smoking, obesity and pregnancy may also increase the risk of thrombosis and should be considered.

Individuals more prone to hypercoagulation of the blood are at increased risk of developing deep vein thrombosis (DVT), which is characterized by a tendency for clots to form in the veins of the legs. Although clots form mainly in the legs, they can also occur in other parts of the body such as the lungs, leading to pulmonary embolism. Venous thrombosis is the main term that includes DVT and pulmonary embolism and its incidence is estimated at 1-2 per 1000 individuals each year, being the third most common cardiovascular disease.

Being a multifactorial condition, there are a number of actions that can help minimize the risk of thrombosis:

  • Healthy lifestyle with a balanced diet and regular exercise.
  • When faced with long periods of sitting, get up and walk around every 1 to 2 hours.
  • Getting out of bed and moving around as soon as possible after surgery or disability.
  • Taking medication for thrombus prevention.
  • Wearing loose-fitting clothing.

The risk of blood hypercoagulation is largely affected by the genetic component. It is known that the presence of mutations such as factor V Leiden or the prothrombin gene mutation 20210G-A are associated with the risk of hereditary thrombophilias.

The Factor V Leiden mutation occurs in the F5 gene and is more frequent in Caucasian populations than in those of other origins, so it is estimated that between 3 and 8% of the European or US Caucasian population carries at least one copy of the mutation.

When the Factor V Leiden mutation occurs in the F5 gene, the mutated Factor V Leiden becomes more resistant to the action of APC (activated protein C with inactivating effect of Factor V Leiden), which promotes the generation of thrombin, an enzyme that promotes blood clotting.

The presence of the factor V Leiden mutation in the F5 gene has been found to be one of the main genetic factors leading to venous thromboembolism (VTE), a disorder that includes deep vein thromboembolism and pulmonary embolisms. VTE is characterized by the abnormal formation of blood clots, which in this case mainly affect the veins of the legs.

On the other hand, the 20210G-A marker has been identified in the F2 gene, which produces the prothrombin protein, a glycoprotein formed in the liver that plays a vital role in the formation of blood clots.The frequency with which this glycoprotein is produced in the liver plays a vital role in the conversion of fibrinogen to fibrin during clot formation, in order to stop bleeding when an injury occurs. The frequency with which this mutation occurs is low, being more common in the population of European descent than in other populations.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

2 variants


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Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369(6475):64-7.

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