АПС-резистентность на фоне коморбидных состояний как возможный предиктор ВТЭО у носительниц мутации фактор V Лейден во время беременности

Аннотация

Целью исследования является определение роли резистентности фактора Vа к активированному протеину С и коморбидности у носительниц мутации FVL(1691)GA в реализации венозных тромбоэмболических осложнений (ВТЭО) во время беременности. Проведено проспективное клиническое когортное исследование 1100 женщин репродуктивного возраста, проанализировано течение и исходы 2707 беременностей. Выделено две когорты: основная группа – 500 пациенток с генотипом FVL(1691)GA, и группа контроля – 600 женщин с генотипом FVL(1691)GG. Носительство мутации FVL(1691)GA при вынашивании беременности статистически значимо ассоциировано с развитием ВТЭО по сравнению с генотипом FVL(1691)GG (RR4,7; р<0,0001). Во всех случаях в период времени, предшествующий эпизоду тромбоза, показатель АПС-резистентности по нормализованному отношению (НО) составлял ≤0,49, в то время как при АПС-резистентности с НО ≥0,5 эпизодов ВТЭО не определено. При возникновении ВТЭО во время гестации носительницы мутации FVL(1691)GA значимо чаще страдают коморбидными состояниями (RR4,5; р<0,0001). Найдено, что венозные тромбозы во время гестации реализуются при условии выраженной АПС-резистентности, обусловленной носительством мутации FVL(1691)GA и коморбидностью. Показатель АПС-резистентности может служить объективным лабораторным маркером, определяющим целесообразность проведения антенатальной тромбопрофилактики. Ключевые слова: мутация фактора V Лейден, генотип FVL(1691)GA; тромбоэмболические осложнения; беременность; коморбидность; АПС-резистентность.

The aim of the study is to determine the role of factor Va resistance to activated protein C and comorbidity in carriers of the FVL (1691) GA mutation in the realization of venous thromboembolic complications (VTEO) during pregnancy. A prospective clinical cohort study of 1100 women of reproductive age was conducted, the course and outcomes of 2,707 pregnancies were analyzed. Two cohorts were identified: the main group – 500 patients with genotype FVL (1691) GA and control group – 600 women, with the genotype FVL (1691) GG. The carriage of the FVL (1691) GA mutation in pregnancy is statistically significantly associated with the development of VTEO compared with the genotype FVL (1691) GG (RR4.7, p <0.0001). In all cases, in the time period preceding the thrombosis episode, the APS resistance index for the normalized ratio (NO) was ≤0.49, while for APS resistance with HO ≥0.5 episodes of WTEO it was not determined. When WTEI occurs during gestation, carriers of the FVL (1691) mutation GA are significantly more likely to suffer from comorbid conditions (RR4.5, p <0.0001). It was found that venous thromboses during gestation are realized under the condition of pronounced APS-resistance caused by the carriage of the mutation FVL (1691) GA and comorbidity. The indicator of APS-resistance can serve as an objective laboratory marker determining the feasibility of conducting antenatal thromboprophylaxis. Key words: mutation factor V Leiden, genotype FVL (1691) GA; thromboembolic complications; pregnancy; comorbidity; APS-resistance.

Об авторах

Николаева Мария Геннадьевна

к.м.н., доцент кафедры акушерства и гинекологии с курсом ДПО Алтайского государственного медицинского университета, г. Барнаул.
656038, г. Барнаул, пр. Ленина, 40.
Тел.: (3852) 566869.
E-mail: nikolmg@yandex.ru

д.м.н., профессор, директор Алтайского филиала Национального медицинского исследовательского центра гематологии, г. Барнаул.
656000, г. Барнаул, ул. Ляпидевского, 1.
Тел.: (3852) 689800
E-mail: xyzan@yandex.ru

д.м.н., профессор, профессор кафедры терапии и общей врачебной практики с курсом ДПО Алтайского государственного медицинского университета, г. Барнаул.
656038, г. Барнаул, пр. Ленина, 40.
Тел.: (3852) 689673.
E-mail: science@agmu.ru

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