The role of genetic markers of thrombophilia in the structure of the causes of placenta-associated complications in pregnant women with thrombocytopenia

Abstract

Hypothesis/Aims of study: Disorders of the hemostatic system continue to occupy one of the leading places in the structure of the causes of infertility and miscarriage. While being associated with reproductive losses, hemostatic disorders are a significant link in the pathogenesis of placenta-associated pregnancy complications. The consumption of platelets and blood clotting factors can be a consequence of inherited thrombophilia and the cause of adverse clinical outcomes of pregnancy. Women with congenital and acquired thrombophilia are at high risk of developing both thrombotic and gestational complications of pregnancy. The aim of this study was to assess the frequency of genetic markers of thrombophilia in pregnant women with thrombocytopenia and to determine the risk of developing obstetric complications depending on thrombophilia gene polymorphisms in the examined women. Study design, materials and methods: This multicenter prospective study involved 299 pregnant women in the third trimester of pregnancy. Two groups of patients were included in the study: the main group (n = 249) consisted of individuals with thrombocytopenia, whereas the control group (n = 50) comprised women with normal platelet counts during physiological pregnancy. All patients underwent a complete clinical, anamnestic and laboratory examination. To identify thrombophilia gene polymorphisms, molecular genetic blood testing was conducted using a biochip developed jointly in the Laboratory of Prenatal Diagnostics of Congenital and Hereditary Diseases, the Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Saint Petersburg, Russia and the V.A. Engelhardt Institute of Molecular Biology, Moscow, Russia. Results: The data obtained from a comparative analysis of genetic markers of thrombophilia indicate that the incidence of mutations in the GPIa platelet receptor gene in pregnant women with thrombocytopenia was significantly higher than that in pregnant women with normal platelet counts and physiological pregnancy (42.5% vs. 14.7%; p = 0.003). The frequency of polymorphisms in genes responsible for disorders in the fibrinolytic system (PAI-1, FGB) was also significantly higher than that in the control group (76.4% vs. 47.0%, p = 0.001; 45.7% vs. 23.5%, p = 0.030, respectively). Conclusion: The revealed high frequency of polymorphisms in the platelet receptor genes and genes responsible for disorders of fibrinolysis system in pregnant women with thrombocytopenia may cause platelet hyperaggregation and hypercoagulation, while being a significant risk factor for placenta-associated complications during pregnancy. The variety of genetic defects that may lead to an unfavorable clinical outcome of pregnancy dictates the need for further study.