Altered platelet and coagulation function in moderate-to-severe COVID-19

Rustem I Litvinov,Svetlana S Sannikova,Izabella A Andrianova,Rafael R Khismatullin,Alina D Peshkova,John W Weisel,Chandrasekaran Nagaswami,Natalia G Evtugina,Svetlana I Safiullina,Alina I Khabirova

doi:10.1038/s41598-021-95397-6

Rustem I Litvinov, Svetlana S Sannikova + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-95397-6

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Abstract

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.

Highlights

The infectious disease caused by the SARS-CoV-2 virus has been named COVID-19
The thrombodynamics assay, which tracks the spatial growth of a plasma clot, revealed that patients with COVID-19 had a significant increase in the clot optical density (Fig. 1a, Table 1a), which was due to hyperfibrinogenemia
In acute COVID-19, hemostatic disorders that were revealed by extensive blood testing correlated with clinical manifestations of the disease, despite continuous low molecular weight heparin (LMWH) and immunosuppressive therapy

Summary

Introduction

The infectious disease caused by the SARS-CoV-2 virus has been named COVID-19. Despite numerous studies, the results of COVID-19 treatment remain mediocre, mainly due to the lack of detailed information on the pathogenesis of the disease, which is different from other known infections in many respects. Despite the proven role of coagulopathies in the clinical course and outcomes of COVID-198–12, some aspects of the pathogenesis of hemostatic disorders in COVID-19 remain understudied. It is not clear if there is a causal relation of hemostatic disorders with local and systemic inflammation and what is the role of inflammatory mediators in the initiation of hypercoagulability and sustaining a high thrombotic potential. A direct correlation between the hypercoagulability and the severity of the disease is not obvious It is unclear whether there is a link between the high thrombotic potential and deaths, especially during heparin therapy. Patients with moderate and severe COVID-19 require continuous laboratory monitoring of hemostasis and personalized use of anticoagulants to prevent or cure overt and latent thrombotic complications

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