Клиническое значение полиморфизма генов фактора V и протромбина
Gematologiâ i transfuziologiâ
In the 1990s, two gene polymorphisms — factor V Leiden (FVLeiden) and prothrombin G20210A (FII G20210A) were recognized as a genetic substrate for the development of thrombophilia. Polymorphism FVLeiden is associated with the development of resistance to anticoagulant action of protein C, and polymorphism FII G20210A with a high level of prothrombin in plasma. In healthy individuals of Caucasian origin, the prevalence of FVLeiden is between 2 and 10%. In patients with venous thromboembolism,
... thromboembolism, the prevalence FVLeiden is about 20%. FII G20210A is found in 1—5% of the general Caucasian population and in 4—18% of patients with venous thromboembolism. These indicators depend on the selection of patients included in the analysis. The relationship between gene polymorphisms and the development of venous thromboembolism in women during pregnancy is discussed. The high risks of venous thromboembolism have been described for women with a homozygous FVLeiden mutation. The study of the activated protein C (APC) and factor V interaction has yielded valuable insights into how perturbations in this association lead to venous thromboembolism. It is now clear that APC exerts anticoagulant effects beyond inactivating factor V by cleaving at R306 and R506, generating inactive FV. Mutation in FVLeiden abrogates this effect. In women with a heterozygous FVLeiden or heterozygous FII G20210A, the risks of venous thromboembolism are significantly low. Regardless of genetic polymorphism, a positive family history of venous thrombosis increases the risk of developing venous thromboembolism during pregnancy. The relationship between genetic polymorphism and nonthrombotic complications developing during pregnancy is discussed. Mutations of FVLeiden and FII G20210A may be associated with the risks of spontaneous abortion and repeated fetal loss.