Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study
Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measu...
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2024-09-01
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| author | Heiko Rühl Christian Bode Tobias Becher Sebastian Eckert Ghaith Mohsen Hannah L. McRae Jens Müller Sara Reda Dirk Loßnitzer Johannes Oldenburg Christian Putensen Bernd Pötzsch |
| author_facet | Heiko Rühl Christian Bode Tobias Becher Sebastian Eckert Ghaith Mohsen Hannah L. McRae Jens Müller Sara Reda Dirk Loßnitzer Johannes Oldenburg Christian Putensen Bernd Pötzsch |
| author_sort | Heiko Rühl |
| collection | DOAJ |
| description | Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, <i>p</i> < 2 × 10<sup>−6</sup>) and non-COVID sepsis (up to 4.7-fold, <i>p</i> < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, <i>p</i> = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, <i>p</i> = 2 × 10<sup>−4</sup>) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (<i>p</i> = 0.036), 6-fold (<i>p</i> = 3 × 10<sup>−7</sup>) and 3-fold (<i>p</i> = 8 × 10<sup>−4</sup>) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis. |
| format | Article |
| id | doaj-art-e0be3497eded43f498675cd68cd8484d |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-09-01 |
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| spelling | doaj-art-e0be3497eded43f498675cd68cd8484d2025-08-20T01:56:05ZengMDPI AGBiomedicines2227-90592024-09-01129198210.3390/biomedicines12091982Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort StudyHeiko Rühl0Christian Bode1Tobias Becher2Sebastian Eckert3Ghaith Mohsen4Hannah L. McRae5Jens Müller6Sara Reda7Dirk Loßnitzer8Johannes Oldenburg9Christian Putensen10Bernd Pötzsch11Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, 53127 Bonn, GermanyFirst Department of Medicine, University Medical Centre Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, 68167 Mannheim, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, 53127 Bonn, GermanyInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, 53127 Bonn, GermanySepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, <i>p</i> < 2 × 10<sup>−6</sup>) and non-COVID sepsis (up to 4.7-fold, <i>p</i> < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, <i>p</i> = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, <i>p</i> = 2 × 10<sup>−4</sup>) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (<i>p</i> = 0.036), 6-fold (<i>p</i> = 3 × 10<sup>−7</sup>) and 3-fold (<i>p</i> = 8 × 10<sup>−4</sup>) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis.https://www.mdpi.com/2227-9059/12/9/1982COVID-19protein Csepsisthrombinthrombophilia |
| spellingShingle | Heiko Rühl Christian Bode Tobias Becher Sebastian Eckert Ghaith Mohsen Hannah L. McRae Jens Müller Sara Reda Dirk Loßnitzer Johannes Oldenburg Christian Putensen Bernd Pötzsch Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study Biomedicines COVID-19 protein C sepsis thrombin thrombophilia |
| title | Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study |
| title_full | Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study |
| title_fullStr | Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study |
| title_full_unstemmed | Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study |
| title_short | Decreased Protein C Pathway Activity in COVID-19 Compared to Non-COVID Sepsis: An Observational and Comparative Cohort Study |
| title_sort | decreased protein c pathway activity in covid 19 compared to non covid sepsis an observational and comparative cohort study |
| topic | COVID-19 protein C sepsis thrombin thrombophilia |
| url | https://www.mdpi.com/2227-9059/12/9/1982 |
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