Оценка взаимосвязи активации коагулофибринолитической системы и асептического воспаления у пациентов с длительно существующей хронической тромбоэмболической легочной гипертензией

Хроническая тромбоэмболическая легочная гипертензия (ХТЭЛГ) является редким заболеванием с неблагоприятным прогнозом. Показана роль моноцитарно-макрофагального воспаления в неполной реканализации острого тромботического поражения легочной артерии и формировании ХТЭЛГ. Остается противоречивой роль коагулофибринолитической системы в патогенезе ХТЭЛГ.

Цель исследования — оценить активность коагулофибринолитической системы и ее взаимосвязь с уровнем моноцитарного хемотаксического фактора 1 (МСP-1), а также тяжестью течения заболевания у пациентов с длительно существующей ХТЭЛГ.

Материалы и методы. В исследование вошло 44 пациента с диагнозом ХТЭЛГ: 21 мужчина (средний возраст 57,0 ± 11,9 года) и 23 женщины (средний возраст 53,8 ± 14,7 года). Диагноз ХТЭЛГ верифицирован согласно клиническим рекомендациям Минздрава России по диагностике и ведению пациентов с легочной гипертензией от 2020 года. Контрольную группу составили здоровые доноры (n = 19, средний возраст 51,0 ± 11,9 года, 10 мужчин, 9 женщин). Все пациенты находились на антикоагулянтной терапии эноксапарином натрия в терапевтической дозе 1 мг/кг подкожно дважды в день. Исследование маркеров системы фибринолиза и воспаления проводилось методом иммуноферментного анализа: активируемый тромбином ингибитор фибринолиза (TAFI), тканевой активатор плазминогена (t-PA), ингибитор активатора плазминогена 1 (PAI-1), моноцитарный хемотаксический фактор 1 (МСР-1).

Результаты. В группе ХТЭЛГ продемонстрировано увеличение уровня t-PA — 6,06 [4,502; 8,03] нг/мл в сравнении с 2,95 [2,75; 3,56] нг/мл у доноров (р = 0,00001). Значимой разницы в уровне PAI-1 и TAFI у больных (34,40 [22,47; 46,43] и 94,67 [90,03; 102,80] нг/мл соответственно) и доноров (24,93 [21,41; 43,88] и 92,68 [87,99; 98,29] нг/мл соответственно) (р = 0,0970 и р = 0,233) не было найдено. Выявлено значимое повышение уровня МСР-1 у больных с ХТЭЛГ относительно доноров (34,95 [31,00; 42,08] против 26,05 [20,40; 31,33] пг/мл соответственно, р = 0,016). Была отмечена корреляция между МСP-1 и показателями фибринолиза t-PA (0,402, р = 0,046), PAI-1 (0,437, р = 0,029). Также показаны корреляции МСP-1 и маркеров фибринолиза с показателями гемодинамики и физической работоспособности: MCP-1 и SvO₂ (–0,574, p = 0,002), MCP-1 и сердечный индекс (–0,614, p = 0,001), дистанция в тесте шестиминутной ходьбы и t-PA (–0,435, p = 0,006).

Заключение. В результате исследования продемонстрирована взаимосвязь МСP-1 с показателями активности коагулофибринолитической системы и тяжестью течения ХТЭЛГ. Полученные данные могут быть использованы для дальнейшего изучения патогенеза посттромбоэмболического синдрома и разработки критериев оценки прогноза у пациентов с ХТЭЛГ.

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