The Role of APC-Resistance for Predicting Venous Thrombosis and Pregnancy Complications in Carriers of Factor V Leiden (1691) G/A Mutation

Abstract

This chapter presents the results of the prospective cohort study of 500 females with factor V Leiden, FVL, 1691 GA genotype, during 2008-2015. The association between FVL (regardless of its laboratory phenotype-factor Va resistance to activated protein C, APC resistance) and the development of VTEC (both outside of and during pregnancy) and gestational complications such as preeclampsia, fetal growth restriction, and miscarriage has been established. Additionally, the leading role of APC resistance degree in the clinical manifestation of FVL 1691 GA genotype as thrombotic events and pregnancy complications has been proved. Based on the data obtained, advanced approaches for the stratification of pregnant women into risk groups for the development of venous thromboembolic complications and pregnancy complications at different gestational ages adjusted for APC resistance degree are proposed. The found patterns can be useful in assessing the need for heparin prophylaxis during pregnancy from the standpoint of personalized medicine.

<p>Clinical and laboratory manifestations of the prothrombin gene mutation in women of reproductive age</p>

“…Earlier, we conducted a research aimed at studying the association between the Leiden mutation laboratory phenotype and the risk of thrombosis in women of reproductive age 28,29. The research lasted 9 years and involved dynamic observation of the cohort of 500 FV Leiden G1691A (FVL G1691A) mutation carriers.…”

Advisory Board conclusion following the discussion "Controversial issues of low molecular weight heparins use in obstetrics"

“…В ряде случаев точечные мутации проявляются лишь на лабораторном уровне, когда меняется структура или функция кодируемого белка, и лишь при мультифакториальном воздействии патологический генотип имеет клиническую реализацию. Так, например, доказано, что клиническая реализация тромботических событий и ПАО при носительстве мутации Лейден возможна только при выраженном лабораторном фенотипе, а именно, при снижении резистентности фактора Vа к активированному протеину С (APC-R), составляющему по нормализованному отношению (НО) меньше 0,49 [20]. Фенотип мутации гена фактора II -это степень активности протромбина.…”