Brief Reports
Vol. 3 No. 3 (2024)
Thrombin generation assay in COVID-19 patients shows a hypocoagulable pattern
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 23 June 2024
Accepted: 2 October 2024
Accepted: 2 October 2024
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Patients with COVID-19 often exhibit coagulopathy, which can significantly impact prognosis. Therefore, investigating coagulation in this context is clinically relevant. The thrombin generation assay (TGA) provides comprehensive data on individual clotting patterns. In our study, we utilized a calibrated automated thrombogram to globally assess coagulation in COVID-19 patients. The study included 67 COVID-19 patients (40 hospitalized in the medical ward and 27 in intensive care units) and 45 blood donors for comparison. Our analysis revealed significant differences in TGA parameters (lag time, time-to-peak, thrombin peak, and endogenous thrombin potential) between patients and blood donors, suggesting a hypocoagulable state in the former. Specifically, COVID-19 patients exhibited prolonged lag time and time-to-peak values, as well as lower thrombin peak and endogenous thrombin potential compared to blood donors (Mann-Whitney test: p<0.05); notably, no significant differences in thrombin generation were observed based on the clinical setting. These findings suggest a reduced capacity for thrombin generation, indicating a consumptive coagulopathy in COVID-19 patients and that in this context, thrombosis is primarily attributable to localized effects in the lungs, platelet activation, and/or prothrombotic endothelial dysfunction. The thrombin generation assay is instrumental in defining coagulation patterns in COVID-19 and may also be applicable to other infectious diseases.
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Citations
Gerber GF, Chaturvedi S. How to recognize and manage COVID-19-associated coagulopathy. Hematology Am Soc Hematol Educ Program 2021:614-20. DOI: https://doi.org/10.1182/hematology.2021000297
Devreese KMJ. COVID-19-related laboratory coagulation findings. Int J Lab Hematol Suppl 1:36-42. DOI: https://doi.org/10.1111/ijlh.13547
Tiscia GL, Favuzzi G, De Laurenzo A, et al. Reduction of ADAMTS13 levels predicts mortality in SARS-CoV-2 patients. TH Open 2020;4:e203-e206. DOI: https://doi.org/10.1055/s-0040-1716379
Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clinical Chemistry 2016;62: 699-707. DOI: https://doi.org/10.1373/clinchem.2015.248625
Hemker HC, Giesen P, Al Dieri R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003;33:4-15. DOI: https://doi.org/10.1159/000071636
White D, MacDonald S, Edwards T, et al. Evaluation of COVID-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays. Int J Lab Hematol 2021;43:123-30. DOI: https://doi.org/10.1111/ijlh.13329
Marongiu F, Grandone E, Barcellona D. Pulmonary thrombosis in 2019-nCoV pneumonia? J Thromb Haemost 2020;18:1511-13. DOI: https://doi.org/10.1111/jth.14818
Wójcik K, Bazan-Socha S, Celejewska-Wójcik N, et al. Decreased protein C activity, lower ADAMTS13 antigen and free protein S levels accompanied by unchanged thrombin generation potential in hospitalized COVID-19 patients. Thromb Res 2023;223:80-86. DOI: https://doi.org/10.1016/j.thromres.2023.01.016
Cohen O, Landau N, Avisahai E, et al. Association between Thrombin Generation and Clinical Characteristics in COVID-19 Patients. Acta Haematol 2023;146:151-60. DOI: https://doi.org/10.1159/000527581
Campello E, Bulato C, Spiezia L, et al. Thrombin generation in patients with COVID-19 with and without thromboprophylaxis. Clin Chem Lab Med 2021;59:1323-30. DOI: https://doi.org/10.1515/cclm-2021-0108
Gris JC, Guillotin F, Dos Santos TP, et al. Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study. Thromb Res 2023;222:85-95. DOI: https://doi.org/10.1016/j.thromres.2022.12.019
Kelliher S, Weiss L, Cullivan S, et al. Non-severe COVID-19 is associated with endothelial damage and hypercoagulability despite pharmacological thromboprophylaxis. J Thromb Haemost 2022;20:1008-14. DOI: https://doi.org/10.1111/jth.15660
Nougier C, Benoit R, Simon M, et al. Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis. J Thromb Haemost 2020;18:2215-9. DOI: https://doi.org/10.1111/jth.15016
Vermeiren P, Vandevelde A, Peperstraete H, Devreese KMJ. Monitoring of heparin therapy beyond the anti-Xa activity assay: Evaluation of a thrombin generation assay. Int J Lab Hematol 2022;44:785-95. DOI: https://doi.org/10.1111/ijlh.13836
Binder NB, Depasse F, Mueller J, et al. Clinical use of thrombin generation assays. J Thromb Haemost 2021;19:2918-29. DOI: https://doi.org/10.1111/jth.15538
van de Berg TW, Hulshof AM, Nagy M, et al. Suggestions for global coagulation assays for the assessment of COVID-19 associated hypercoagulability. Thromb Res 2021;201:84-9. DOI: https://doi.org/10.1016/j.thromres.2021.02.026
Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost 2020;18:2103-9. DOI: https://doi.org/10.1111/jth.14975
Thachil J. Lessons learnt from COVID-19 coagulopathy. EJHaem 2021;2:577584. DOI: https://doi.org/10.1002/jha2.228
Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020;18:1023-6. DOI: https://doi.org/10.1111/jth.14810
Supporting Agencies
Italian Ministry of HealthHow to Cite
1.
Tiscia GL, Colaizzo D, De Laurenzo A, Cappucci F, Fischetti L, Chinni E, et al. Thrombin generation assay in COVID-19 patients shows a hypocoagulable pattern. Bleeding Thromb Vascul Biol [Internet]. 2024 Oct. 22 [cited 2025 Dec. 26];3(3). Available from: https://www.btvb.org/btvb/article/view/145
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