Fibrin Network Formation and Lysis in Septic Shock Patients
Background: Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient’s fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9540 |
| _version_ | 1797521328601825280 |
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| author | Julie Brogaard Larsen Mathies Appel Aggerbeck Kim Michael Larsen Christine Lodberg Hvas Anne-Mette Hvas |
| author_facet | Julie Brogaard Larsen Mathies Appel Aggerbeck Kim Michael Larsen Christine Lodberg Hvas Anne-Mette Hvas |
| author_sort | Julie Brogaard Larsen |
| collection | DOAJ |
| description | Background: Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient’s fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to assess fibrinolysis in septic shock patients using a plasma-based fibrin clot formation and lysis (clot–lysis) assay and investigate the association between clot–lysis parameters and other haemostatic markers, organ dysfunction and mortality. Methods: This was a prospective cohort study including adult septic shock patients (<i>n</i> = 34). Clot–lysis was assessed using our plasma-based in-house assay. Platelet count, activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, fibrin D-dimer, antithrombin, thrombin generation, circulating fibrinolysis markers and organ dysfunction markers were analysed. Disseminated intravascular coagulation score, Sequential Organ Failure Assessment (SOFA) score and 30-day mortality were registered. Results: Three distinct clot–lysis profiles emerged in the patients: (1) severely decreased fibrin formation (flat clot–lysis curve), (2) normal fibrin formation and lysis and (3) pronounced lysis resistance. Patients with abnormal curves had lower platelet counts (<i>p</i> = 0.05), more prolonged aPTT (<i>p</i> = 0.04), higher lactate (<i>p</i> < 0.01) and a tendency towards higher SOFA scores (<i>p</i> = 0.09) than patients with normal clot–lysis curves. Fibrinogen and fibrin D-dimer were not associated with clot–lysis profile (<i>p</i> ≥ 0.37). Conclusion: Septic shock patients showed distinct and abnormal clot–lysis profiles that were associated with markers of coagulation and organ dysfunction. Our results provide important new insights into sepsis-related fibrinolysis disturbances and support the importance of assessing fibrinolytic capacity in septic shock. |
| first_indexed | 2024-03-10T08:10:00Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:00Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-af396e77f371403db8586975cf22320d2023-11-22T10:45:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217954010.3390/ijms22179540Fibrin Network Formation and Lysis in Septic Shock PatientsJulie Brogaard Larsen0Mathies Appel Aggerbeck1Kim Michael Larsen2Christine Lodberg Hvas3Anne-Mette Hvas4Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, DenmarkThrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, DenmarkDepartment of Anaesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, DenmarkThrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus, DenmarkBackground: Septic shock patients are prone to altered fibrinolysis, which contributes to microthrombus formation, organ failure and mortality. However, characterisation of the individual patient’s fibrinolytic capacity remains a challenge due to a lack of global fibrinolysis biomarkers. We aimed to assess fibrinolysis in septic shock patients using a plasma-based fibrin clot formation and lysis (clot–lysis) assay and investigate the association between clot–lysis parameters and other haemostatic markers, organ dysfunction and mortality. Methods: This was a prospective cohort study including adult septic shock patients (<i>n</i> = 34). Clot–lysis was assessed using our plasma-based in-house assay. Platelet count, activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, fibrin D-dimer, antithrombin, thrombin generation, circulating fibrinolysis markers and organ dysfunction markers were analysed. Disseminated intravascular coagulation score, Sequential Organ Failure Assessment (SOFA) score and 30-day mortality were registered. Results: Three distinct clot–lysis profiles emerged in the patients: (1) severely decreased fibrin formation (flat clot–lysis curve), (2) normal fibrin formation and lysis and (3) pronounced lysis resistance. Patients with abnormal curves had lower platelet counts (<i>p</i> = 0.05), more prolonged aPTT (<i>p</i> = 0.04), higher lactate (<i>p</i> < 0.01) and a tendency towards higher SOFA scores (<i>p</i> = 0.09) than patients with normal clot–lysis curves. Fibrinogen and fibrin D-dimer were not associated with clot–lysis profile (<i>p</i> ≥ 0.37). Conclusion: Septic shock patients showed distinct and abnormal clot–lysis profiles that were associated with markers of coagulation and organ dysfunction. Our results provide important new insights into sepsis-related fibrinolysis disturbances and support the importance of assessing fibrinolytic capacity in septic shock.https://www.mdpi.com/1422-0067/22/17/9540sepsisfibrinolysisfibrin clot lysis timeplasminogenplasminogen activator inhibitor 1disseminated intravascular coagulation |
| spellingShingle | Julie Brogaard Larsen Mathies Appel Aggerbeck Kim Michael Larsen Christine Lodberg Hvas Anne-Mette Hvas Fibrin Network Formation and Lysis in Septic Shock Patients International Journal of Molecular Sciences sepsis fibrinolysis fibrin clot lysis time plasminogen plasminogen activator inhibitor 1 disseminated intravascular coagulation |
| title | Fibrin Network Formation and Lysis in Septic Shock Patients |
| title_full | Fibrin Network Formation and Lysis in Septic Shock Patients |
| title_fullStr | Fibrin Network Formation and Lysis in Septic Shock Patients |
| title_full_unstemmed | Fibrin Network Formation and Lysis in Septic Shock Patients |
| title_short | Fibrin Network Formation and Lysis in Septic Shock Patients |
| title_sort | fibrin network formation and lysis in septic shock patients |
| topic | sepsis fibrinolysis fibrin clot lysis time plasminogen plasminogen activator inhibitor 1 disseminated intravascular coagulation |
| url | https://www.mdpi.com/1422-0067/22/17/9540 |
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