Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19
Abstract Hypercoagulability and endothelial dysfunction are strongly involved in the worsening of the clinical condition in COVID-19 patients. In severe cases, the inflammatory process triggers the release of angiopoietin 2, which could decrease circulating thrombomodulin (TM), a major regulatory me...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-15679-1 |
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| author | Ana Marco-Rico Adrián Montaño Francisco López-Jaime Ihosvany Fernández-Bello Pascual Marco-Vera |
| author_facet | Ana Marco-Rico Adrián Montaño Francisco López-Jaime Ihosvany Fernández-Bello Pascual Marco-Vera |
| author_sort | Ana Marco-Rico |
| collection | DOAJ |
| description | Abstract Hypercoagulability and endothelial dysfunction are strongly involved in the worsening of the clinical condition in COVID-19 patients. In severe cases, the inflammatory process triggers the release of angiopoietin 2, which could decrease circulating thrombomodulin (TM), a major regulatory mechanism in thrombin generation. Although some studies have described an increased TM resistance, further data are needed to obtain robust results. The objective of our study was to evaluate TM resistance in hospitalized COVID-19 patients using the thrombin generation test and its correlation with development of any severe clinical events (SCE). Forty-seven hospitalized COVID-19 patients were included (median age was 59 years (50–75); 42.6% women). Measurement of endogenous thrombin potential (ETP) revealed that 54.8% of patients had a percentage (%) of ETP inhibition < 40%, suggesting TM resistance. 23% (23%) of patients (n = 11/47) presented at least one SCE. Significant resistance to TM was observed in patients with SCE: percentage (%) of ETP inhibition was 24.3% vs. 47.6% (p = 0.019) in the non-SCE group. Furthermore, lower percentage (%) of ETP inhibition significantly correlated with increased clot stiffness (r= -0.372, p = 0.0167). The percentage (%) of ETP inhibition was a strong predictor of SCE, with an AUC of 0.803 (95%CI: 0.670–0.936). To conclude, thrombin generation can be a powerful tool for risk stratification in hospitalized COVID-19 patients. In addition, increased TM resistance, quantified by a lower percentage (%) of ETP inhibition is strongly associated with the development of SCE and shows promise as a powerful and new independent marker of poor prognosis. |
| format | Article |
| id | doaj-art-5ac9cf7ee38844acbc06220e0a7ba41a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5ac9cf7ee38844acbc06220e0a7ba41a2025-08-20T03:42:38ZengNature PortfolioScientific Reports2045-23222025-08-011511910.1038/s41598-025-15679-1Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19Ana Marco-Rico0Adrián Montaño1Francisco López-Jaime2Ihosvany Fernández-Bello3Pascual Marco-Vera4Thrombosis and Hemostasis Department, Hematology Service, University General HospitalThrombosis and Hemostasis Department, Hematology Service, Regional University HospitalThrombosis and Hemostasis Department, Hematology Service, Regional University HospitalBiomedical Research Institute (ISABIAL)Biomedical Research Institute (ISABIAL)Abstract Hypercoagulability and endothelial dysfunction are strongly involved in the worsening of the clinical condition in COVID-19 patients. In severe cases, the inflammatory process triggers the release of angiopoietin 2, which could decrease circulating thrombomodulin (TM), a major regulatory mechanism in thrombin generation. Although some studies have described an increased TM resistance, further data are needed to obtain robust results. The objective of our study was to evaluate TM resistance in hospitalized COVID-19 patients using the thrombin generation test and its correlation with development of any severe clinical events (SCE). Forty-seven hospitalized COVID-19 patients were included (median age was 59 years (50–75); 42.6% women). Measurement of endogenous thrombin potential (ETP) revealed that 54.8% of patients had a percentage (%) of ETP inhibition < 40%, suggesting TM resistance. 23% (23%) of patients (n = 11/47) presented at least one SCE. Significant resistance to TM was observed in patients with SCE: percentage (%) of ETP inhibition was 24.3% vs. 47.6% (p = 0.019) in the non-SCE group. Furthermore, lower percentage (%) of ETP inhibition significantly correlated with increased clot stiffness (r= -0.372, p = 0.0167). The percentage (%) of ETP inhibition was a strong predictor of SCE, with an AUC of 0.803 (95%CI: 0.670–0.936). To conclude, thrombin generation can be a powerful tool for risk stratification in hospitalized COVID-19 patients. In addition, increased TM resistance, quantified by a lower percentage (%) of ETP inhibition is strongly associated with the development of SCE and shows promise as a powerful and new independent marker of poor prognosis.https://doi.org/10.1038/s41598-025-15679-1COVID-19ThrombosisThrombin generationThrombomodulin resistanceSevere clinical events |
| spellingShingle | Ana Marco-Rico Adrián Montaño Francisco López-Jaime Ihosvany Fernández-Bello Pascual Marco-Vera Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 Scientific Reports COVID-19 Thrombosis Thrombin generation Thrombomodulin resistance Severe clinical events |
| title | Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 |
| title_full | Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 |
| title_fullStr | Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 |
| title_full_unstemmed | Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 |
| title_short | Thrombomodulin resistance as a novel prothrombotic pathway in COVID-19 |
| title_sort | thrombomodulin resistance as a novel prothrombotic pathway in covid 19 |
| topic | COVID-19 Thrombosis Thrombin generation Thrombomodulin resistance Severe clinical events |
| url | https://doi.org/10.1038/s41598-025-15679-1 |
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