Quantitative and qualitative changes in blood cells associated with COVID-19

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Abstract


Aim. To establish the relationship of hematological disorders with the pathogenesis, course and outcomes of COVID-19.

Methods. We examined 235 hospitalized patients with moderate and severe forms of acute COVID-19 receiving anticoagulants and immunosuppressive drugs. We studied the full blood cell counts and morphology along with the platelet function by flow cytometry in comparison with the clinical features and synthesis of inflammatory markers. To assess platelet contractility, blood clot contraction (retraction) kinetics was used in combination with scanning electron microscopy of platelets and blood clots.

Results. Hemolytic anemia, neutrophilia and lymphopenia were associated with immature erythrocytes and leukocytes, indicating activation of hematopoiesis. Contraction of blood clots in COVID-19 was impaired, especially in severe and lethal cases, as well as in the presence of comorbidities, including myeloproliferative and coronary heart diseases and acute cerebrovascular disease. In male patients, the changes in clot contraction were more pronounced. Suppression of clot contraction correlated directly with anemia and coagulopathy, including a high D-dimer level, which confirms the pathogenetic significance of blood clot contraction in COVID-19. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with chronic platelet activation and secondary platelet dysfunction. The structure and cellular composition of blood clots depended on the extent of contraction; clots with impaired contraction were porous, had a low content of deformed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin.

Conclusion. Blood cells undergoing both quantitative and qualitative changes are involved in the pathogenesis of COVID-19; the suppressed platelet-driven contraction of intravital blood clots may be a part of the prothrombotic mechanisms.


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About the authors

N G Evtugina

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Author for correspondence.
Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

S S Sannikova

City Clinical Hospital No. 16

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

A D Peshkova

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

S I Safiullina

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University; Medical Center “Aibolit”

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia; Kazan, Russia

I A Andrianova

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

G R Tarasova

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

R R Khismatullin

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

Sh M Abdullaeva

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

R I Litvinov

Institute of Fundamental Medicine and Biology of Kazan (Volga Region) Federal University

Email: natalja.evtugyna@gmail.com

Russian Federation, Kazan, Russia

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Supplementary files

Supplementary Files Action
1.
Рис. 1. Оптическая система для измерения кинетики контракции сгустка крови: A — примеры изображений сгустка на разных стадиях контракции; Б — типичная кинетическая кривая контракции сгустка крови и её ­основные параметры

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2.
Рис. 2. Параметры контракции сгустков крови пациентов с COVID-19 (n=215) и здоровых доноров (n=40): А — степень контракции; Б — лаг-период; В — площадь под кривой; Г — средняя скорость; результаты представлены в виде медианы и интерквартильного интервала (25-й и 75-й процентили); *p <0,001, критерий Манна–Уитни

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3.
Рис. 3. Зависимость параметров контракции сгустков крови пациентов с COVID-19 от количества тромбоцитов: А — степень контракции; Б — лаг-период; В — площадь под кривой; Г — средняя скорость; результаты представлены в виде медианы и интерквартильного интервала (25-й и 75-й процентили); *p <0,05, **p <0,01, ***p <0,001, метод ­Краскела–Уоллиса с последующим тестом Данна для парных сравнений.

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4.
Рис. 4. Репрезентативные микрофотографии сгустков крови у больных COVID-19 с низкой (13%) (А) и высокой (49%) (Б) степенями контракции, полученные с помощью сканирующей электронной микроскопии: А — сгусток с высокой порозностью, большим содержанием фибрина (Ф) и сохранением фракции двояковогнутых эритроцитов (Эр); Б — сгусток плотный, без межклеточных пор, с большим содержанием многогранных эритроцитов — полиэдроцитов (П)

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5.
Рис. 5. Репрезентативные микрофотографии частично активированных (А) и покоящихся (Б) тромбоцитов из крови пациентов с COVID-19, полученные с помощью сканирующей электронной микроскопии

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© 2021 Evtugina N.G., Sannikova S.S., Peshkova A.D., Safiullina S.I., Andrianova I.A., Tarasova G.R., Khismatullin R.R., Abdullaeva S.M., Litvinov R.I.

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