Статья
Структурно-функциональные изменения эритроцитов, ассоциированные с развитием тромбоза и нарушениями гемостаза
Данные клинических и экспериментальных исследований последнего десятилетия заставляют пересмотреть роль клеток красной крови в развитии тромбозов и нарушений системы гемостаза. Особую актуальность данное направление приобретает в период пандемии COVID-19.Цель обзора – представить данные о структурно-функциональных и количественных изменениях эритроцитов, ассоциированных с развитием тромбозов и нарушениями гемостаза, в том числе у пациентов с коронавирусной инфекцией. Приведены результаты научных исследований, посвященных изучению морфологических, функциональных сдвигов в клетках красной крови, влияющих на гемостаз и тромбоз. Эти нарушения включают в себя показатель количества эритроцитов или гематокрит (модулирующий реологию крови через ее вязкость) и качественные изменения, такие как деформируемость, агрегация эритроцитов, экспрессия адгезивных белков и фосфатидилсерина, высвобождение внеклеточных микровезикул, гемолиз, состояние пьезорецепторов, модуляция биодоступности оксида азота. Показана связь изменения параметров эритроцитов, возникающих при хранении крови, с возможными тромботическими последствиями при переливании крови. Самые последние исследования касаются сдвига показателей красной крови при инфицировании SARS-CoV-2, которые связаны с развитием тромбозов: прикрепление вируса и амплификация вирусных белков в клетках-предшественниках эритропоэза; активация стрессового эритропоэза с увеличением доли ядерных эритроцитарных клеток до 42 %; активация процессов окисления белка полосы 3 с его избыточным расщеплением, окисление и расщепление альфа-цепи спектрина, анкирина; изменения липидной архитектуры мембраны и снижение антиоксидантной активности эритроцита, что опосредует нарушение деформируемости клеток и выcвобождения АТФ; снижение возможности эритроцитов к секреции оксида азота; уменьшение уровня сфинголипидов эритроцитарной мембраны; избыточная продукция микровезикул с тканевым фактором; нарастание ригидности эритроцитов с нарушением высвобождения внутриэритроцитарного оксида азота вследствие атаки вирусом SARS-CoV-2 1-бета-цепи гемоглобина и захватом порфирина с потенциальным ингибированием гема; увеличение экспрессии на поверхности эритроцитов активированных компонентов комплемента C3b и C4d, иммуноглобулина IgG, что ухудшает деформируемость клеток; прикрепление эритроцитов через Толл-подобный рецептор 9 к нейтрофильным внеклеточным ловушкам, способствующее тромбообразованию; повышенная презентация фосфатидилхолина на мембранах эритроцитов, что облегчает сборку теназного и протромбиназного комплексов, способствуя выработке тромбина; увеличение уровня внутриклеточного кальция со стимуляцией образования микровезикул с протромботическим потенциалом. Представленные данные свидетельствуют о значимой роли изменений параметров эритроцитов в развитии нарушений гемостаза, особенно в период пандемии COVID-19, что делает клетки красной крови мишенью для терапии и предполагает изменение акцентов тактики ведения пациентов с тромбозами.
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