Thrombophilia for factor V Leiden (Factor V Leiden thrombophilia) - Gen F5

Thrombophilia by factor V Leiden is the most common form of hereditary thrombophilia. Individuals affected by this process develop DVT, mainly affecting the lower limbs, but also elsewhere (thromboembolism) as lung, brain, eyes, liver or kidneys. However, approximately 10% of individuals with genetic abnormality Factor V Leiden never develop such thrombosis. This process has also been associated with an increased risk of miscarriage and other complications during pregnancy such as preeclampsia, slow fetal development, or abruption, although most women with thrombophilia for factor V Leiden have normal pregnancies.

This process is due to a particular mutation in the F5 gene, located on the long arm of chromosome 1 (1q23). This gene encodes the factor V clotting, synthesized in the liver, circulating blood in an inactive form until the activation of the coagulation system resulting from any vascular damage occurs. When this (factor Va) is activated factor interacts with activated factor X (Factor Xa), forming a complex which converts prothrombin to thrombin, then thrombin converts fibrinogen to fibrin. Factor Va (activated), is controlled by activated protein C (APC: activated protein C) thereby reducing the clotting process, preventing clots generated is too increase. The APC cleavages causing exerts its action at specific locations on Factor V. When cleaves at position 534 of the protein, interacts with the APC protein to inactivate factor VIIIa.

In thrombophilia for factor V Leiden, there is a single mutation in an amino acid of the protein Factor V, changing the amino acid arginine for the amino acid glutamic acid in position 534 (arg534glu; R534Q) mutation causes a factor V abnormal can not inactivated by activated protein C (APC), so the factor V remains active and can not prevent further activated factor VIIIa, and coagulation process is not stopped. The risk of the manifestations of the process depend on the number of genomic copies altered by each cell, so that if only has the mutation one of the two alleles (heterozygous), the risk of developing the process is less than when the copies of both alleles are affected (homozygous).

Other factors also increase the risk of developing blood clots in people with thrombophilia by factor V Leiden. These factors include increasing age, obesity, injury, surgery, smoking, pregnancy and oral contraceptives or hormone replacement therapy. The risk of abnormal blood clots is also much higher in people who have a combination of the factor V Leiden mutation and another in the F5 gene. Moreover, the risk is increased in people who have the factor V Leiden, along with a mutation in another gene involved in the coagulation system.

Other mutations F5 gene prevents the synthesis of normal factor V from the functional point of view or reduce their blood concentration. When these mutations occur in both copies of chromosome (alleles) of factor V deficiency occurs, in which there is no normal clotting and those affected manifest abnormal bleeding. In some patients it described the combination of factor V Leiden., Along with other mutations causing factor V deficiency, and in these individuals is increased clotting process.

The likelihood of developing an abnormal blood clot depends on whether a person is carrying one or two copies of the factor V Leiden in each cell. People who inherit two copies of the mutation, one from each parent, are at increased risk of developing a clot that people who inherit one copy of the mutation. Given that approximately 1 in 1000 people per year in the general population will develop abnormal blood clot, the presence of a copy of the factor V Leiden increases the risk of 3 to 8 per 1,000 while having two copies of the mutation may increase the risk to 80 per 1,000.

Tests in IVAMI: IVAMI performed in detecting the R534Q mutation associated with thrombophilia for factor V Leiden, corresponding exon by PCR, or by the complete PCR amplification of the exons of the F5 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).