GENETIC TESTING FOR THROMBOPHILIA

For tombofilia means a predisposition to the development of thrombosis , and can be inherited in our genes. La trombosi è un accumulo organizzato di piastrine , fibrin , globuli rossi e bianchi all’interno di un vaso arterioso o venoso. The severity of the disease will of course be correlated with the seat , the extension and combination with other pathological processes. In the perspective of prevention can be carried out to date of genetic testing on blood sample or buccal swab which are in addition to the usual blood tests for the evaluation of thrombophilic state. The main mutations ripetto now seek to Factor V Leiden , al Fattore II ( Prothrombin) and the enzyme MTHFR for Homocysteine.

OF THE FACTOR V LEIDEN ( G1691A)

The Factor V Leiden (activated) is a very important cofactor for the conversion of prothrombin to thrombin in the process of thrombus formation. It is activated , passing from factor V to Vattivato , favorito della proteina Cattivata che si forma dalla Proteina C sotto stimolo della Proteina S. The antithrombotic effect triggered by Protein Cattivata is expressed by the “cutting” of FattoreV into three parts of which one is represented dall'amminoacido arginine in position 506. The genetic mutation leads to the substitution of arginine with glutamine. The latter preventing the “cutting” Protein Cattivata gives the Factor V a higher prothrombotic activity. This variant is called G1691A and has a frequency of 2-4% in Europe( heterozygosity 3% and homozygosity 1:5000). The thrombophilic risk is increased by 8 times for subjects carrying the mutation in the heterozygous and 80 times for those homozygous. The mutation becomes particularly important in association with other conditions such as pregnancy thrombophilic , use of oral contraceptives , surgeries , trauma , varicose veins of the lower limbs. In pregnancy , also a condition of heterozygosity , predisposes to spontaneous abortions.

FACTOR II – Prothrombin (G20210A)

Il fattore II o Protrombina svolge un ruolo fondamentale nella coagulazione poiché la sua trasformazione in Trombina favorisce il passaggio del Fattore I (Fibrinogen) Fibrin in with consequent formation of coagulo.La mutation is manifested by the substitution of a guanine with an adenine at position 20210 from which G20210A. The frequency of the variant is low about 1 %con una percentuale di eterozigoti del 3% mentre l’omozigosi è molto rara.Per gli eterozigoti c’è un rischio aumentato di 3 times to develop a venous thrombosis , of 5 times for ischemic stroke, of 5 times for myocardial infarction in young women, of 1,5 times for men, of 7 volte nei diabetici, of 10 times to thrombosis of the cerebral veins and 149 volte in donne che assumono contraccettivi orali.

MTHFR – methylenetetrahydrofolate (C667T – A1298C)

Homocysteine ​​is an amino acid whose accumulation would increase the risk of venous thrombosis , infarto miocardico e ictus. The conditional is necessary because many studies are still underway to ascertain the true correlation between the accumulation of the amino acid and pathological events. However, it seems that the deposit of homocysteine ​​in the intravascular endothelial injury and it increases platelet adhesiveness processes. The homocysteine ​​to methionine in the transformation process also needs of’ MTHFR. I difetti genetici portano alla diminuzione della disponibilità dell’enzima con accumulo di omocisteina. A genetic mutation of the enzyme MTHFR is the mutation from cytosine to thymine in position 667 which leads to a reduction of activity by about 60% resulting in the accumulation of homocysteine. In Europe we have a percentage of 3% with 45% of heterozygosity and 10% homozygosity. Another mutation is the substitution of an adenine with a cytosine in position 1298 resulting in decreased levels of MTHFR and elevated homocysteine. The damage caused dall'iperomocisteinemia would be gradual and initially asymptomatic. The cardiovascular risk occurs however in subjects with reduced folates. It is therefore important to take folic acid in order to minimizzarei risks.

CONCLUSIONS

All genetic variants exhibited can occur singly or in combination. Obviously the cardiovascular risk increases with the mutations , their presentation (homozygosity / heterozygosity) and all'associazioni of other predisposing factors. In the presence of inherited thrombophilia is useful to perform tests in order to implement a lifestyle or treatment conforming or indications of further controls to minimize the cardiovascular risks. The indication for the tests shall be given by a doctor, and possibly supplemented with additional examinations. Genetic testing can be performed via overexposed buccal swab or blood sample from an alternative to reporting in a few days.