[Peculiarities of blood coagulation disorders in patients with COVID-19].

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.

Hemostatic disorders are associated with the course and outcomes of COVID-19

Background : Thrombotic events are common in COVID-19 but little understood. Aims : To reveal if coagulopathies relate to the course and outcomes of COVID-19. Methods : We examined 235 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Informed consent was obtained and the study was approved by the Ethics Committee of K(V)FU. Hemostasis was assessed using a thrombodynamics assay, thromboelastography, fibrinogen and Ddimer levels, prothrombin time, and soluble fibrin complexes (ethanol gelation test). Blood clot contraction (retraction) kinetics was performed along with electron microscopy of platelets and clots and platelet flow cytometry. The hemostatic parameters were correlated with biochemical and hematological tests. Results : Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about 1/4 cases were associated with a high level of C-reactive protein, which may impede coagulation in vitro and mask the inflammatory thrombophilia in vivo . Contraction of blood clots was hindered and incomplete in about 1/2 patients, especially in severe and fatal cases. Suppression of clot contraction correlated directly with prothrombotic parameters, including a high D-dimer level. A decrease in the platelet contractility was mainly due to moderate thrombocytopenia in combination with chronic platelet activation and secondary 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 uncompact intravital clots are more obstructive but could also be prone to bleeding. 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. Conclusions : The results obtained i) confirm the importance of hemostatic disorders in COVID-19;ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction;iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.

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

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. © 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/ licenses/by/4.0/.