rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2022-08-01rpcardio-2786Research ArticleORIGINAL STUDIESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯPulmonary Vascular Thrombosis in COVID-19: Clinical and Morphological ParallelsТромбоз сосудистого русла легких при COVID-19: клинико-морфологические параллелиhttps://orcid.org/0000-0003-3537-7409ПорембскаяО. Я.PorembskayaO. Ya.

Порембская Ольга Ярославна.

Санкт-Петербург.

eLibrary SPIN 9775-1057

Olga Ya. Porembskaya.

St-Petersburg.

eLibrary SPIN 9775-1057

porembskaya@yandex.ruhttps://orcid.org/0000-0002-6337-104XКравчукВ. Н.KravchukV. N.

Кравчук Вячеслав Николаевич.

Санкт-Петербург.

eLibrary SPIN 4227-2846

Viacheslav N. Kravchuk.

St-Petersburg.

eLibrary SPIN 4227-2846

https://orcid.org/0000-0002-5476-6058ГальченкоМ. И.GalchenkoM. I.

Гальченко Максим Иванович.

Санкт-Петербург.

eLibrary SPIN 8858-2916

Maxim I. Galchenko.

St-Petersburg.

eLibrary SPIN 8858-2916

https://orcid.org/0000-0001-8389-3841ДеевР. В.DeevR. V.

Деев Роман Вадимович.

Санкт-Петербург.

eLibrary SPIN 2957-1687

Roman V. Deev.

St-Petersburg.

eLibrary SPIN 2957-1687

https://orcid.org/0000-0002-9171-8338ЧесноковМ. Ш.ChesnokovM. Sh.

Чесноков Михаил Шакирович.

Санкт-Петербург.

Mikhail S. Chesnokov.

St-Petersburg.

https://orcid.org/0000-0002-2751-5587АванесянА. В.AvanesyanA. V.

Аванесян Альберт Вадимович.

Санкт-Петербург.

eLibrary SPIN 5704-3320

Albert V. Avanesyan.

St-Petersburg.

eLibrary SPIN 5704-3320

https://orcid.org/0000-0002-5358-7218ЛобастовК. В.LobastovK. V.

Лобастов Кирилл Викторович.

Москва.

eLibrary SPIN 2313-0691

Kirill V. Lobastov.

Moscow.

eLibrary SPIN 2313-0691

https://orcid.org/0000-0003-1567-1328ЦаплинС. Н.TsaplinS. N.

Цаплин Сергей Николаевич.

Москва.

eLibrary SPIN 8827-1385

Sergey N. Tsaplin.

Moscow.

eLibrary SPIN 8827-1385

https://orcid.org/0000-0002-5542-1502ЛаберкоЛ. А.LaberkoL. A.

Лаберко Леонид Александрович.

Москва.

eLibrary SPIN 8941-5729

Leonid A. Laberko.

Moscow.

eLibrary SPIN 8941-5729

https://orcid.org/0000-0003-3008-5124ЕрмаковВ. С.ErmakovV. S.

Ермаков Валерий Сергеевич.

Санкт-Петербург.

eLibrary SPIN 9095-3330

Valerii S. Ermakov.

St-Petersburg.

eLibrary SPIN 9095-3330

https://orcid.org/0000-0001-6955-4595ПашовкинаО. В.PashovkinaO. V.

Пашовкина Ольга Викторовна.

Москва.

eLibrary SPIN 3448-9764

Olga V. Pashovkina.

Moscow.

eLibrary SPIN 3448-9764

https://orcid.org/0000-0002-1306-1502СчастливцевИ. В.SchastlivtsevI. V.

Счастливцев Илья Вениаминович.

Москва.

eLibrary SPIN 7329-6994

Ilya V. Schastlivtsev.

Moscow.

eLibrary SPIN 7329-6994

https://orcid.org/0000-0002-9880-516XСайгановС. А.SayganovS. A.

Сайганов Сергей Анатольевич.

Санкт-Петербург.

eLibrary SPIN 2174-6400

Sergey A. Sayganov.

St-Petersburg.

eLibrary SPIN 2174-6400

Северо-Западный Государственный Медицинский Университет им. И.И. МечниковаРоссияMechnikov's North-Western State Medical UniversityRussian FederationСанкт-Петербургский Государственный Аграрный УниверситетРоссияState Agrarian UniversityRussian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова; Клиническая больница №1 (Волынская) Управления делами Президента Российской ФедерацииРоссияPirogov Russian National Research Medical University; Clinical hospital no.1 of the Presidents Administration of Russian FederationRussian FederationКлиническая больница №1 (Волынская) Управления делами Президента Российской ФедерацииРоссияClinical hospital no.1 of the Presidents Administration of Russian FederationRussian Federation202207092022184376384Copyright © Porembskaya O.Y., Kravchuk V.N., Galchenko M.I., Deev R.V., Chesnokov M.S., Avanesyan A.V., Lobastov K.V., Tsaplin S.N., Laberko L.A., Ermakov V.S., Pashovkina O.V., Schastlivtsev I.V., Sayganov S.A., 20222022Порембская О.Я., Кравчук В.Н., Гальченко М.И., Деев Р.В., Чесноков М.Ш., Аванесян А.В., Лобастов К.В., Цаплин С.Н., Лаберко Л.А., Ермаков В.С., Пашовкина О.В., Счастливцев И.В., Сайганов С.А.Porembskaya O.Y., Kravchuk V.N., Galchenko M.I., Deev R.V., Chesnokov M.S., Avanesyan A.V., Lobastov K.V., Tsaplin S.N., Laberko L.A., Ermakov V.S., Pashovkina O.V., Schastlivtsev I.V., Sayganov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/2786Aim

Aim. We aimed to study the histological and thrombotic changes in lung vessels in patients who died with COVID-19, to access the correlation between anticoagulation therapy (ACT) and thrombotic events (TE), treatment results, clinical and laboratory patients' characteristics.

Material and Methods

Material and Methods. We retrospectively analyzed treatment results of patients hospitalized with COVID-19 and lung vessel samples of the deceased patients. Dynamic changes and highest levels of D-dimer and fibrinogen were studied in its correlation with the disease severity according to SOFA score, computer tomographic (CT) results, lung, renal and hepatic dysfunction. The association between different doses of ACT and treatment results, laboratory indicators and thrombotic events was accessed. The histological lung vessels examination was performed using Martius Scarlet Blue (MSB)staining.

Results

Results. 313 patients were included in the study (61 patients died). The median age of hospitalized patients was 60 years (IQR 51-66 years). The frequency of the intravitallyconfirmed TE was 4,8%. The strong statistical association was revealed between D-dimer level and 3-4 points SOFA score, patients' mortality, oxygen support requirement, CT3-CT4 pneumonia, glomerular filtration rate and TE. There was no mortality in patients with D-dimer normal references, but in cases with three times elevation reached 13%, 48,5% - in cases with 3-6 times elevation and 64,6% - in cases with more than 6 times elevation. The strong statistical association was registered between fibrinogen and SOFA score, CT 3-4 pneumonia, patients' mortality. D-dimer and fibrinogen levels demonstrated weak correlation. There was no statistical correlation between prophylactic, intermediate and therapeutic ACT and D-dimer and fibrinogen levels, CT results, patients' mortality. MSBstaining was used in 36 deceased patients tissue samples. 1394 lung vessels were analyzed. Lung vessels thrombi persisted in samples of all 36 patients (100%). Vessels with the diameter 3,5-30 mm were thrombosed in 7%, with the diameter 0,034-0,84 mm - in 48%, with the diameter 0,85-3,4 mm - in 45%. The frequency of thrombi persisted 06 hours, 6-12 hours, 12-18hours, 18-24 hours and more than 24 hours was12%, 14%, 62%, 5% and 7% respectively.

Conclusion

Conclusion. Thrombi of different ages from fresh to organized were observed in one third of lung vessels in all deceased patients. Lung vessels thrombosis plays an important role in pathogenesis and thanatogenesis of COVID-19. The D-dimer level correlates with lung, renal dysfunction, patients' mortality and doesn't show any correlation with ACT and can be accepted as a criterion of lung vessel thrombotic progression.

Цель

Цель. Изучить гистологические изменения и особенности тромботического поражения сосудистого русла легких у пациентов, скончавшихся от новой коронавирусной инфекции (COVID-19), оценить связь разных доз антикоагулянтных препаратов и процессов тромбообразования, результатов лечения и динамики ряда клинических и лабораторных показателей этих больных.

Материал и методы

Материал и методы. Проведен ретроспективный анализ результатов стационарного лечения пациентов с COVID-19 в сочетании с морфологическим исследованием образцов легочной ткани скончавшихся больных. Изучена динамика и пиковые уровни Д-димера и фибриногена, тяжесть заболевания по шкале SOFA, распространенности пневмонии при компьютерной томографии (КТ), органная дисфункция легких, почек и печени. Оценена связь лечебных, промежуточных и профилактических дозировок антикоагулянтной терапии (АКТ) с течением и исходом заболевания, динамикой лабораторных показателей. Проведено гистологическое исследование сосудистого русла легких [окраска Martius Scarlet Blue (MSB) по Лендруму].

Результаты

Результаты. В исследование включены 313 пациентов (61 пациент скончался); медиана возраста 60 лет (межквартильный диапазон 51-66 лет). Частота прижизненно подтвержденных тромботических событий (ТС) - 4,8%. Выявлена сильная статистически значимая связь уровня D-димера с тяжестью в 3-4 балла по SOFA, летальным исходом, потребностью в кислородной поддержке, распространенностью поражения при КТ, снижением скорости клубочковой фильтрации, ТС. Летальный исход не наблюдался при нормальных значениях D-димера, наступал в 13% случаев при его повышении до 3 раз, в 48,5% - до 3-6 раз, в 64,6% - при увеличении более чем в 6 раз. Для высокого уровня фибриногена сильная статистически значимая связь прослеживалась с тяжестью по шкале SOFA в 3-4 балла, КТ3 и КТ4 степенях тяжести пневмонии, летальным исходом. Уровни D-димера и фибриногена продемонстрировали слабую корреляцию. Проведение АКТ в разных режимах (профилактическая, промежуточная и лечебная) не показало статистически значимой связи с уровнями D-димера, фибриногена, динамикой изменений при КТ, с общей летальностью. В гистологических препаратах 36 скончавшихся пациентов применена окраска MSB. Оценено 1394 сосуда. У всех 36 больных (100%) в сосудах разного калибра обнаружены тромбы различной давности. В сосудах калибра 3,5-30 мм тромбы встречались в 7%, калибра 0,034-0,84 мм - в 48%, среднего калибра 0,85-3,4 мм - в 45%. Доля тромбов возрастом 0-6 ч, 6-12 ч, 12-18 ч, 18-24 ч, >24 ч составила 12%, 14%, 62%, 5% и 7% соответственно.

Заключение

Заключение. Тромботические изменения в системе легочной артерии (ЛА) обнаруживались у всех скончавшихся пациентов, они поражали около трети сосудов легочного русла и представляли собой тромбы различной степени зрелости. Тромботические процессы в сосудистом русле легких играют значимую роль в патогенезе и танатогенезе при COVID-19. Критерием прогрессирования тромбоза в системе ЛА при COVID-19 может являться уровень D-димера, нарастание которого коррелировало с тяжестью легочной дисфункции, тромботическими изменениями легких, риском летального исхода и не зависело от характера АКТ.

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The authors declare that there are no conflicts of interest present.