Peculiarities of blood coagulation disorders in patients with COVID-19

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Abstract

Aim. To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19.

Materials and methods. We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes.

Results. Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation.

Conclusion. The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

About the authors

Natalia G. Evtugina

Kazan Federal University

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-4950-3691

мл. науч. сотр.

Russian Federation, Kazan

Svetlana S. Sannikova

City Hospital №16

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-0668-1877

врач

Russian Federation, Kazan

Alina D. Peshkova

Kazan Federal University

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-8790-1818

канд. биол. наук, науч. сотр. Института фундаментальной медицины и биологии

Russian Federation, Kazan

Svetlana I. Safiullina

Kazan Federal University; Medical Center “Aibolit”

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0003-4657-0140

канд. мед. наук, ст. науч. сотр. Института фундаментальной медицины и биологии, врач-гематолог

Russian Federation, Kazan

Izabella A. Andrianova

Kazan Federal University

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0003-3973-3183

канд. биол. наук, науч. сотр. Института фундаментальной медицины и биологии

Russian Federation, Kazan

Gulzada R. Tarasova

Kazan Federal University

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0003-3599-1599

врач клиники ФГАОУ ВО КФУ

Russian Federation, Kazan

Alina I. Khabirova

Kazan Federal University

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-7243-8832

мл. науч. сотр. Института фундаментальной медицины и биологии

Russian Federation, Kazan

Aleksandr G. Rumyantsev

Dmitry Rogachev National Medical Research Center of Pediatric Hematology

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-1643-5960

акад. РАН, д-р мед. наук, проф., президент ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева»

Russian Federation, Moscow

Fazoil I. Ataullakhanov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; Center for Theoretical Problems of Physico-Chemical Pharmacology

Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0002-6668-0948

чл.-кор. РАН, д-р биол. наук, проф., науч. рук. ФГБУН ЦТП ФХФ РАН, зав. отд. биофизики и системной биологии и лабораторией биофизики ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева

Russian Federation, Moscow

Rustem I. Litvinov

Kazan Federal University

Author for correspondence.
Email: natalja.evtugyna@gmail.com
ORCID iD: 0000-0003-0643-1496

д-р мед. наук, проф., гл. науч. сотр. Института фундаментальной медицины и биологии

Russian Federation, Kazan

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2. Fig. 1. Parameters of thrombodynamics in COVID-19 patients (n=215) and healthy donors (n=20): a – clot density, b – the stationary clot growth rate, c – the initial clot growth rate, d – clot size, e – lag time. Hereinafter in tables 2, 3, 5: results are presented as a median and interquartile range (25 and 75th percentiles). *p<0.01; **p<0.001, Mann–Whitney U-test.

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3. Fig. 2. Characteristic thromboelastograms (TEGs) of a COVID-19 patient and a healthy donor, illustrating the decelerated clotting and an increase in the clot strength in the COVID-19 plasma sample.

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