Diagnostics of the Factor V Leiden mutation (c.1601G>A / p.Arg534Gln)

Clinical significance:

Virulent thrombosis is a serious health problem, affecting 1:1,000 peopleb per year. Blood coagulation in blood vessels is possible due to a slowing down of blood flow, damage to the blood vessel wall or an increase in blood clotting (Virchow's triad). There are numerous external factors that favor thrombosis, including immobilization (after surgery, as a result of bedridden illnessesb, in a long journeyve), cardiac arrhythmias (especially atrial fibrillationw), cancer, age over 60, hormone therapy in women, pregnancy and puerg, obesity and lipid disorders, varicose veins of the lower extremities, intravascular manipulation (catheterization, venflon).

There is also a known propensity for genetically determined increased blood clotting, caused by common polymorphic variants in the genese: prothrombin (F2) on chromosome 11p11 (a variant in the non-coding region of 20110G>A) in 1-5% of the European population, the proacellarin gene (F5) on chromosome 1q23 (1691G>A, a Leiden-type mutation) in 10-15% of the European population (25% of all casesThrombophilia and 50% of familial cases) and methylenetetrahydrofolate reductase (MTHFR) on chromosome 1p36 (thermolabile variants 677C>T and 1298A>C) in 30-40% of the European population. Inheritance of propensity to thrombosis dominant, more frequent symptoms in women.

Prone to thrombosis is usually asymptomatic, with probably 90-95% of carriers having no symptomsw before age 50. Typical concerns are venous thrombosis (in the deep veins of the extremities) and pulmonary embolism occurring at any time in life, on³ with the presence of multiple risk factors. Sometimes a less typical localization is observed, such as veins of the mgovt, liver, abdominal cavity, reticulargovt or arterial vessels. The presence of one mutation increases the risk of a thrombotic episode by about 5-fold in adults and about 3-fold in children. If more than one mutation is present, the risk of thrombosis multiplies.

Recurrences of thrombosis are observed in 1/4 -1/3 of patients, usually within a few years, and there is a clear risk of a repeat episode in pregnant women who have previously had thrombotic symptoms. In addition, women who carry the mutation have an independent risk of spontaneous abortions (after 10 weeks), a hypertrophic state, placental detachment, intrauterine fetal growth retardation, with symptoms in about 10% of women, unrelated to venous thrombosis. In homozygotes, symptoms are of similar severity, usually occur earlier, but the risk of symptomsw is many times higher.

The indication for the test is:

• diagnosis of casesof venous thrombosis, especially unprovoked before the age of 50 or recurrent casesof venous thrombosis or thrombosis of unusual location or thrombosis associated with hormonal disorders (pregnancy, puerg, use of estrogenin replacement therapy or contraception);
• diagnosis of cases of reproductive failure, especially recurrent miscarriages after 10 weeks, severe casesof pre-eclampsia, placental detachment or significant intrauterine growth retardation and somecongenital malformations;
• diagnosis of casesof "isolated" pulmonary embolism and casesof myocardial infarction or stroke in smoking women before the age of 50;
• Family testing: detection of F2, F5 or MTHFR gene mutations in a relative in families with symptomatic thrombosis before age 50. It is advisable to test asymptomatic siblings of the carrier, especially before planned surgeries, and women related to the carrier before planned pregnancy or planned estrogeningestion;

The test is available in 4 variants, usually used sequentially:

• analysis of Leiden mutation in the F5 gene and 20210G>A mutation in the F2 gene (2-allele test);
• analysis of the 677C>T (p.A222V) and 1298A>C (p.E429A) mutations in the MTHFR gene (3rd-line test, recommended especially in cases of elevated blood homocysteine levels);
• analysis of Leiden mutations in the F5 gene, 20210G>A in the F2 gene, and 677C>T and 1298A>C mutations in the MTHFR gene (4th-line test, interchangeable with the previous variantsw);