Цель исследования: изучить связь феномена резистентности фактора Vа к активированному протеину С (АПС-резистентность) при носительстве мутации гена FVL (1691) GA с клинической реализацией во время беременности тромботических событий и гестационных осложнений, таких как преэклампсия, задержка развития плода и невынашивание беременности. Материалы и методы. Проведено проспективное клиническое когортное исследование 1100 беременных. Выделено 2 когорты: основная группа – 500 пациенток с генотипом FVL (1691) GA и группа контроля – 600 женщин с генотипом FVL (1691) GG. Результаты. Медиана нормализованного отношения (НО) АПС-резистентности в контрольной группе у беременных с генотипом FVL (1691) GG колебалась в диапазоне 1,0→0,86. У беременных – носителей генотипа FVL (1691) GA этот показатель был достоверно ниже – 0,55→0,48 (р < 0,05). У пациенток при НО > 0,5 течение беременности было благоприятным. Более выраженная АПС-резистентность (НО ≤ 0,49) ассоциировалась с гестационными осложнениями. Заключение. Полученные данные по АПС-резистентности позволяют относить в группу высокого риска по тромботическим и акушерским осложнениям женщин – носительниц мутации фактора V Лейден (1691) не только с генотипом АА, но и с генотипом GA. AПС-резистентность ≤ 0,49 (по показателю НО) при носительстве мутации фактора V Лейден (1691) GA может рассматриваться как прогностический маркер развития гестационных осложнений с наибольшей точностью при сроке 7-8 недель беременности. Aim: to study during pregnancy the relationship between factor Va resistance to activated protein C (APC-resistance) in carriers of FVL gene mutation (1691) GA with clinical realization of thrombotic events and gestational complications such as preeclampsia, fetal growth retardation and miscarriage. Materials and methods. A prospective clinical cohort study of 1100 pregnant women was performed. Two cohorts were identified: main group – 500 patients with FVL genotype (1691) GA and control group – 600 women with FVL genotype (1691) GG. Results. The median of normalized ratio (NR) of APC resistance in the control group with FVL genotype (1691) GG ranged from 1.0→0.86. In pregnant women – the carriers of FVL genotype (1691) GA this parameter was significantly lower – 0.55→0.48 (р < 0.05). In patients with HO > 0.5 the course of pregnancy was favorable. More expressed APS-resistance (НО ≤ 0,49) was associated with gestational complications. Conclusion. The obtained data on APC-resistance allow to classify women – the carriers of Factor V Leiden (1691) mutation, not only with the AA genotype but also with GA genotype as the group of high risk for thrombotic and obstetric complications. APC resistance ≤ 0.49 (according NR) with the carriage of Factor V Leiden mutation (1691) GA can be considered as a prognostic marker for the development of gestational complications with the greatest accuracy at a period of 7-8 weeks of gestation.
Цель исследования: изучить лабораторный фенотип редких мутаций Лейдена [FVL А(1961)A] и гена протромбина [FII А(20210)A] при их клинической реализации в виде тромбозов. Материалы и методы. Проведено многоцентровое проспективное наблюдательное исследование, включающее 80 носителей редких генетических форм тромбофилий: FVL А(1961)A (n = 31), FII А(20210)A (n = 10) и компаунд FII G(20210)A + FVL G(1691)A (n = 39). У всех пациентов исследована резистентность фактора Va к активированному протеину С (APC-R) по нормализованному отношению (НО) и уровень активности протромбина в плазме крови в состоянии физического здоровья и в случае эпизода тромботического события. Результаты. Определена ассоциативная связь развития тромботических событий со снижением НО при оценке APC-R как у гомозиготных носителей мутации Лейден (Ме = 0,35; 95% ДИ = 0,31–0,37 по НО), так и гетерозиготных компаундов (Ме = 0,43; 95% ДИ = 0,42–0,45 по НО). Заключение. Лабораторный мониторинг пациентов с редкими формами генетических тромбофилий позволяет выделить группу высокого тромбогенного риска, нуждающуюся в пролонгированной тромбопрофилактике. Objectives: to study the laboratory phenotype of rare Leiden mutation [FVL A(1961)A] and the prothrombin gene mutation [FII А(20210)A] implementating clinically as thrombosis. Patients / Methods. A multicenter prospective observational study included 80 carriers of rare genetic kinds of thrombophilia: FVL A(1961)A (n = 31), prothrombin FII А(20210)A (n = 10) and the compound FII G(20210)A + FVL G(1691)A (n = 39). All patients were tested for the factor Va resistance to activated protein C (APC-R), normalized ratio (NR), and the plasma prothrombin activity (%) in healthy conditions and in the case of thrombotic event. Results. An associative relation between the development of thrombotic events and a decrease in NR was determined when assessing APC-R, both in homozygous carriers of the Leiden mutation (Me = 0.35; 95% CI = 0.31–0.37 in NR) and heterozygous compounds (Me = 0.43; 95% СI = 0.42–0.45 in NR). Conclusions. Laboratory follow up for patients with rare kinds of genetic thrombophilias allows to identify a group at high thrombogenic risk requiring prolonged thromboprophylaxis.
Aim of the study – to establish the features of inheritance of the F5L:G(1961)A and F2:G(20210)A genotypes and to assess their influence on the course and outcomes of pregnancy.Materials and methods. The object of the study was 70 mother–child pairs: 50 women, carriers of the F5L:G(1961)A mutation, and their children; 20 female patients, carriers of the F2:G(20210)A mutation, their children. Additionally, 18 families of women, carriers of the factor V Leiden mutation, in three generations were studied.Results. Carriage of the F5:(1961)GA and F2:(20210)GA genotypes in fetuses is associated with the risk of developing gestational complications in their mothers, which are primarily realized when the maternal laboratory phenotype is manifested. A higher frequency of occurrence of the minor allele A20210 of the FII gene was determined in children than in the older generation (p = 0,0006).
Introduction. A prothrombin-mutant genotype is a known risk factor in gestational complications.Aim — efficacy assessment in pregravid heparin prevention of pre-eclampsia (PE) and foetal growth retardation (FGR) in females with F2G20210A genotype and suprathreshold prothrombin activity.Patients and methods. A single-centre randomised controlled study enrolled 80 pregnant women carrying prothrombin F2G20210A. The inclusion criterion was a pregravid plasma prothrombin activity > 171 %. The study cohort consisted of 50 women (mean age 31.2 ± 3.7 years) receiving low molecular-weight heparin (LMWH) in menstrual cycle at weight-based elevated prevention doses. A comparison group comprised 30 pregnant women (mean age 31.3 ± 2.9 years) not receiving LMWH prophylaxis.Results. A pregravid start of LMWH treatment at high prophylactic doses in F2G20210A genotype carriers with prothrombin activity > 171 % allowed an absolute risk reduction (ARR) of PE by 46.7 % [p = 0.0001; number needed to treat (NNT): 2.1; 95 % confidence interval (CI) 3.4–1.56], severe PE by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)] and FGR by 30.7 % [p = 0.0001; NTT: 3.3; 95 % CI (6.7–2.2)].Conclusion. Use of LMWH is justified in prevention of placenta-mediated complications in F2G20210A genotype carriers with a suprathreshold-high prothrombin activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.