ДЕТЕРМИНАНТЫ ВЫСОКОЙ И НИЗКОЙ ОСТАТОЧНОЙ РЕАКТИВНОСТИ ТРОМБОЦИТОВ ПРИ ПРИЕМЕ КЛОПИДОГРЕЛА В 1-2 СУТКИ ИНФАРКТА МИОКАРДА
Аннотация
Цель исследования. Определение клинических и лабораторных факторов, влияющих на высокую и низкую остаточную реактивность тромбоцитов при приеме клопидогрела у пациентов в первые-вторые сутки инфаркта миокарда (ИМ). Материал и методы. Обследованы 405 пациентов с ИМ в возрасте от 31 года до 74 лет, 322 – мужчины и 83 женщины. Группа 1 – пациенты с низкой остаточной реактивностью тромбоцитов (НОРТ) – 89 чел., группа 2 – пациенты с оптимальной реактивностью тромбоцитов (ОРТ) – 223 чел., группа 3 – пациенты с высокой остаточной реактивностью тромбоцитов (ВОРТ) – 93 человека. Проводили агрегометрию на агрегометре Multiplate (Германия) с несколькими индукторами агрегации, общий анализ крови и исследование тромбоцитарных индексов – на гемоанализаторе Sysmex XS-500i, Япония. Исследование уровня растворимого лиганда CD40 (sСD40L) и sP-селектина выполнено у 140 пациентов, фактора фон Виллебранда (ФВ) и эндотелина-1 – у 150 чел. на иммуноферментном анализаторе Sunrise TECAN, Австрия. Все исследования проводились при поступлении пациентов в стационар в первые-вторые сутки ИМ (не ранее чем через 12 часов от назначения нагрузочной дозы клопидогрела). Результаты. При проведении однофакторного линейного регрессионного анализа выявлены факторы, независимо влияющие на значение ADP-test: возраст (β=-0,21, 95% ДИ: -0,42 – -0,0095; р=0,04); общий холестерин (β=1,4, 95% ДИ: 0,26-2,56; р=0,04); количество лейкоцитов (β=0,57, 95% ДИ: 0,003-1,14; р=0,049); гемоглобин (β=-0,16, 95% ДИ: -0,27 – -0,044; р=0,0067); количество тромбоцитов (β=1,4, 95% ДИ: 0,26-2,56; р=0,04); тромбокрит (PCT) (β=76,8, 95% ДИ: 41,5-112,1; р=0,000024); TRAP-test (β=0,4, 95% ДИ: 0,33-0,46; р<0,000001); CD40L (β=0,044, 95% ДИ: 0,013-0,074; р=0,005); sР-селектин (β=2,3, 95% ДИ: 0,63- 3,97; р=0,007); ФВ (β=0,06, 95% ДИ: 0,016-0,11; р=0,0085). Для определения вероятности развития ВОРТ построено уравнение бинарной регрессии с логит-функцией связи на основании данных наблюдений за выборкой из 398 пациентов, куда вошли следующие показатели: возраст, количество лейкоцитов, значения среднего объема тромбоцитов (MPV), ширины распределения тромбоцитов по объему (PDW), значения TRAP-test и уровень креатинина. При пороге отсечения по вероятности p=0,4746 чувствительность построенной модели составила 74,2%, специфичность – 74,1%, точность классификации – 74,1%, площадь под ROC-кривой – 0,795 (ДИ: 0,745-0,844). Для определения вероятности развития НОРТ построено уравнение бинарной регрессии с логит-функцией связи на основании данных наблюдений за выборкой из 143 пациентов, куда вошли следующие показатели: количество лейкоцитов, значения MPV и TRAP-test, уровень фибриногена и ФВ. При пороге отсечения по вероятности p=0,5589 чувствительность данной модели составила 84,6%, специфичность – 77,8%, точность классификации – 79,0%, площадь под ROC-кривой – 0,826 (ДИ: 0,747-0,905). Выводы. В первые-вторые сутки ИМ выявлено 22% пациентов с чрезмерным ответом на клопидогрел и 23% с недостаточным ответом на клопидогрел. Детерминанты ВОРТ – возраст, количество лейкоцитов, значения MPV, PDW, TRAP-test и уровень креатинина. Детерминантами НОРТ являются количество лейкоцитов, значения MPV, TRAP-test, уровень фибриногена и ФВ.
Литература
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