The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients
ABSTRACT Septic shock is characterised by abnormal coagulation activation with defective fibrinolysis, leading to a high mortality rate. Cellular activation triggers the release of extracellular vesicles (EVs) conveying both procoagulant and fibrinolytic activities. We investigated whether the balan...
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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| Series: | Journal of Extracellular Vesicles |
| Online Access: | https://doi.org/10.1002/jev2.70073 |
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| author | Romaric Lacroix Coralie Judicone Karim Harti Souab Amandine Bonifay Anderson Loundou Tarik Bouriche Sylvie Cointe Loris Vallier Evelyne Abdili Laurent Arnaud Stéphane Robert Philippe Poncelet Charlotte Grosdidier Pierre Morange Eva Cochery‐Nouvellon Sylvie Bouvier Jean‐Christophe Gris Jean‐Yves Lefrant Marc Leone Jacques Albanese Françoise Dignat‐George |
| author_facet | Romaric Lacroix Coralie Judicone Karim Harti Souab Amandine Bonifay Anderson Loundou Tarik Bouriche Sylvie Cointe Loris Vallier Evelyne Abdili Laurent Arnaud Stéphane Robert Philippe Poncelet Charlotte Grosdidier Pierre Morange Eva Cochery‐Nouvellon Sylvie Bouvier Jean‐Christophe Gris Jean‐Yves Lefrant Marc Leone Jacques Albanese Françoise Dignat‐George |
| author_sort | Romaric Lacroix |
| collection | DOAJ |
| description | ABSTRACT Septic shock is characterised by abnormal coagulation activation with defective fibrinolysis, leading to a high mortality rate. Cellular activation triggers the release of extracellular vesicles (EVs) conveying both procoagulant and fibrinolytic activities. We investigated whether the balance between these activities, termed EV‐coagulolytic balance (EV‐CLB), predicts day‐90 mortality in 225 septic shock patients included in a multicentre prospective study. EV‐CLB, quantified as a ratio of TF‐dependent thrombin generation to uPA‐dependent plasmin generation, was higher in non‐survivors than in survivors at 24 h (2.78 [0.86–16.1] a.u. vs. 0.97 [0.34–2.18] a.u., p < 0.001). Moreover, survivors showed a significant decrease in EV‐CLB from H0 to H48 in contrast to non‐survivors. EV‐CLB was a better predictor than EV‐associated–procoagulant and ‐fibrinolytic activities taken individually and better correlated with sepsis severity markers such as SAPS II and lactate levels. Multivariate Cox regression models including severity markers and comorbidities confirmed EV‐CLB as an independent predictor of mortality in septic shock patients. Interestingly, subgroup analysis revealed EV‐CLB's strong prognostic value in peritonitis, biliary and urinary tract infections and Gram‐negative sepsis. Despite challenges in EV measurement requiring technical advancement for clinical translation, EV‐CLB represents a potential novel biomarker to guide individualised therapy targeting coagulation/fibrinolysis imbalance in septic shock. Trial Registration: This trial was registered at ClinicalTrials.gov identifier: NCT02062970 |
| format | Article |
| id | doaj-art-ecd7a8056063467e99862c3405bc8677 |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-ecd7a8056063467e99862c3405bc86772025-08-20T03:56:49ZengWileyJournal of Extracellular Vesicles2001-30782025-06-01146n/an/a10.1002/jev2.70073The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock PatientsRomaric Lacroix0Coralie Judicone1Karim Harti Souab2Amandine Bonifay3Anderson Loundou4Tarik Bouriche5Sylvie Cointe6Loris Vallier7Evelyne Abdili8Laurent Arnaud9Stéphane Robert10Philippe Poncelet11Charlotte Grosdidier12Pierre Morange13Eva Cochery‐Nouvellon14Sylvie Bouvier15Jean‐Christophe Gris16Jean‐Yves Lefrant17Marc Leone18Jacques Albanese19Françoise Dignat‐George20C2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceR and T Department BioCytex Marseille FranceIntensive Care Unit CHU La Timone, APHM Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceCEReSS ‐ Center for Studies and Research on Health Services and Quality of Life EA3279 Aix‐Marseille University Marseille FranceR and T Department BioCytex Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceDepartment of Hematology Biogenopole, CHU La Timone, APHM Marseille FranceDepartment of Hematology Biogenopole, CHU La Timone, APHM Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceR and T Department BioCytex Marseille FranceDepartment of Hematology CHU Nord, APHM Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceDepartment of Haematology CHU Nimes, Univ Montpellier Nîmes FranceDepartment of Haematology CHU Nimes, Univ Montpellier Nîmes FranceDepartment of Haematology CHU Nimes, Univ Montpellier Nîmes FranceUR‐UM103 IMAGINE, Univ Montpellier, Division of Anesthesia Critical Care, Pain and Emergency Medicine Nîmes University Hospital Montpellier FranceDepartment of Anesthesiology and Intensive Care CHU Nord, APHM Marseille FranceIntensive Care Unit CHU La Timone, APHM Marseille FranceC2VN, INSERM 1263, INRA 1260 Aix‐Marseille University Marseille FranceABSTRACT Septic shock is characterised by abnormal coagulation activation with defective fibrinolysis, leading to a high mortality rate. Cellular activation triggers the release of extracellular vesicles (EVs) conveying both procoagulant and fibrinolytic activities. We investigated whether the balance between these activities, termed EV‐coagulolytic balance (EV‐CLB), predicts day‐90 mortality in 225 septic shock patients included in a multicentre prospective study. EV‐CLB, quantified as a ratio of TF‐dependent thrombin generation to uPA‐dependent plasmin generation, was higher in non‐survivors than in survivors at 24 h (2.78 [0.86–16.1] a.u. vs. 0.97 [0.34–2.18] a.u., p < 0.001). Moreover, survivors showed a significant decrease in EV‐CLB from H0 to H48 in contrast to non‐survivors. EV‐CLB was a better predictor than EV‐associated–procoagulant and ‐fibrinolytic activities taken individually and better correlated with sepsis severity markers such as SAPS II and lactate levels. Multivariate Cox regression models including severity markers and comorbidities confirmed EV‐CLB as an independent predictor of mortality in septic shock patients. Interestingly, subgroup analysis revealed EV‐CLB's strong prognostic value in peritonitis, biliary and urinary tract infections and Gram‐negative sepsis. Despite challenges in EV measurement requiring technical advancement for clinical translation, EV‐CLB represents a potential novel biomarker to guide individualised therapy targeting coagulation/fibrinolysis imbalance in septic shock. Trial Registration: This trial was registered at ClinicalTrials.gov identifier: NCT02062970https://doi.org/10.1002/jev2.70073 |
| spellingShingle | Romaric Lacroix Coralie Judicone Karim Harti Souab Amandine Bonifay Anderson Loundou Tarik Bouriche Sylvie Cointe Loris Vallier Evelyne Abdili Laurent Arnaud Stéphane Robert Philippe Poncelet Charlotte Grosdidier Pierre Morange Eva Cochery‐Nouvellon Sylvie Bouvier Jean‐Christophe Gris Jean‐Yves Lefrant Marc Leone Jacques Albanese Françoise Dignat‐George The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients Journal of Extracellular Vesicles |
| title | The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients |
| title_full | The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients |
| title_fullStr | The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients |
| title_full_unstemmed | The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients |
| title_short | The Procoagulant and Fibrinolytic Balance of Extracellular Vesicles Predicts Mortality in Septic Shock Patients |
| title_sort | procoagulant and fibrinolytic balance of extracellular vesicles predicts mortality in septic shock patients |
| url | https://doi.org/10.1002/jev2.70073 |
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