Tissue factor, D-dimer, and other participants and markers of hemocoagulation at the crossroad of coagulation and fibrinolysis pathways in severe COVID-19

Abstract

Summary. Introduction. This study is devoted to investigating the mechanisms of COVID‐19‐associated coagulopathy and is based on the experience of the Altai Branch of National Medical Research Center for Hematology obtained in 2021–2022 with the participation of a multidisciplinary team. Aim: to trace the patterns of the hemostatic response to SARS‐CoV‐2 invasion in a random sample of patients during the first 24 hours after admission to the intensive care unit (ICU) of a COVID‐19 hospital. Materials and Methods. This observational two‐center study was conducted in 2021–2022 in 96 patients aged 22 to 80 years. The examination was performed within the first 24 hours after admission to the ICU of a COVID‐19 hospital, in patients with a verified severe or extremely severe COVID‐19. A panel of 32 laboratory methods was used, including the assessment of markers of inflammatory response and endothelial dysfunction, as well as parameters of the plateletvascular, coagulation, anticoagulant, and fibrinolytic components of hemostatic system. Results. The mortality rate recorded during the first 7 days after hospitalization was 53%. The course of COVID‐19 infection was accompanied by increases of varying magnitude in plasma levels of several inflammatory markers: C‐reactive protein (CRP), interleukins (interleukin, IL) IL‐1β, IL‐6 as well as neopterin, with the degree of their elevation ranging from 27.6% (for IL‐1β) up to a 90‐fold increase (for IL‐6) relative to normal control values. Endotheliopathy markers — endothelin‐1, von Willebrand factor (vWF), and thrombomodulin were markedly elevated, along with plasma levels of tissue factor (TF) of 5.1‐fold and by a 14.6% decrease in the functional potential of its inhibitor TFPI (tissue factor pathway inhibitor). Notably, these changes did not include a decrease in platelet count or fibrinogen concentration, but were accompanied by more than a 7‐fold increase in D‐dimer level. Among physiological anticoagulants, the most prominent finding was a decrease in protein S activity (by 55.9%). At the same time, both the activity and antigen level of urokinase plasminogen activator (u‐PA) were increased, along with an elevation of plasminogen activator inhibitor‐1 (PAI‐1) and thrombin‐activatable fibrinolysis inhibitor (TAFI) potential (by 18.5%). Conclusion. The mechanisms of COVID‐19‐associated coagulopathy are complex and unusual from the standpoint of traditional concepts of systemic blood coagulation activation in severe infectious diseases. The absence of critical coagulation abnormalities in cytokine storm, along with divergent responses of the anticoagulant and fibrinolytic systems and high mortality, may be characterized as a thrombotic microangiopathy with abnormally high D‐dimer generation. This may contribute to a better understanding of the hemostatic response to external factors in human pathology as a whole.

For citation: Momot D.A., Mamaev A.N., Neimark M.I., Fedorov D.V., Shakhmatov I.I., Belozerskaya G.G., Momot A.P. Tissue factor, D‐dimer, and other participants and markers of hemocoagulation at the crossroad of coagulation and fibrinolysis pathways in severe COVID‐19. Tromboz, gemostaz i reologiya. 2026;(1):56–68. (In Russ.).

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