Mitochondrial Dysfunction in Trauma-related Coagulopathy
Study Details
Study Description
Brief Summary
Bleeding control often poses a great challenge for clinicians due to trauma-induced blood clotting disorder (TIC), a condition that is present in one-third of bleeding trauma patients. As platelets are considered as central mediators in TIC, the understanding of mitochondria-mediated processes in thrombocytes may disclose new therapeutic targets in the management of severely injured patients. The investigators hypothesize that mitochondrial dysfunction occurs in the platelets of trauma patients with TIC. The investigators intend to quantitatively characterize the derangements of mitochondrial functions in TIC; and assess the relation between mitochondrial respiration and clinical markers of platelet function
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Detailed Description
Hemorrhage control often poses a great challenge for clinicians due to trauma-induced coagulopathy (TIC), a condition that is present in one-third of bleeding trauma patients. As platelets are considered as central mediators in TIC, the understanding of mitochondria-mediated processes in thrombocytes may disclose new therapeutic targets in the management of severely injured patients. The investigators hypothesize that mitochondrial dysfunction occurs in the platelets of trauma patients with TIC. The investigators intend to quantitatively characterize the derangements of mitochondrial functions in TIC; and assess the relation between mitochondrial respiration and clinical markers of platelet function measured with aggregometry, viscoelastic tests and conventional laboratory analysis.
Study Design
Outcome Measures
Primary Outcome Measures
- Association between mitochondrial functions and aggregation capacity of platelets [72 hours]
The association between the results of high-resolution respirometry (The activity of respiratory complexes, the ATP synthase activity (OxPhos), the electron transport chain capacity and coupling of mitochondria) and numerical parameters of ROTEM aggregometry (AUC, MS and A6 in TRAPTEM) at 0, 24, 48, and 72 hours post-admission will constitute our primary outcome.
Secondary Outcome Measures
- Association between platelet mitochondrial functions and clot formation ability [72 hours]
The association between the results of high-resolution respirometry (The activity of respiratory complexes, the ATP synthase activity (OxPhos), the electron transport chain capacity and coupling of mitochondria) and results of viscoelastic assays (CT, CFT, α-angle, A10, MCF, LI30 and ML in INTEM, EXTEM, APTEM, FIBTEM) at 0, 24, 48, and 72 hours post-admission will serve as secondary outcome.
- Association between platelet mitochondrial functions and conventional laboratory markers of hemostasis [72 hours]
The association between the results of high-resolution respirometry (The activity of respiratory complexes, the ATP synthase activity (OxPhos), the electron transport chain capacity and coupling of mitochondria) and conventional markers of hemostasis (prothrombin time (PT), International Normalized Ratio (INR)) at 0, 24, 48, and 72 hours post-admission will serve as secondary outcome.
- Relation between platelet mitochondrial functions and mortality [72 hours]
The association between the results of high-resolution respirometry (The activity of respiratory complexes, the ATP synthase activity (OxPhos), the electron transport chain capacity and coupling of mitochondria) and 72-hour mortality will serve as secondary outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Trauma patients
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Injury Severity Score (ISS) 16 or greater,
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age of 18 years or greater,
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hemorrhage confirmed with extended focused assessment with sonography in trauma (eFAST) or computer tomography (CT)
Exclusion Criteria:
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Traumatology, University of Szeged | Szeged | Hungary | 6720 |
Sponsors and Collaborators
- Petra Hartmann MD Ph.D.
Investigators
- Study Director: Endre Prof. Dr. Varga, M.D,Ph.D,DSc, Department of Traumatology, University of Szeged
- Principal Investigator: Petra Dr. Hartmann, M.D., Ph.D., Department of Traumatology, University of Szeged
Study Documents (Full-Text)
None provided.More Information
Publications
- Barile CJ, Herrmann PC, Tyvoll DA, Collman JP, Decreau RA, Bull BS. Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2539-43. doi: 10.1073/pnas.1120645109. Epub 2012 Jan 30.
- Kornblith LZ, Moore HB, Cohen MJ. Trauma-induced coagulopathy: The past, present, and future. J Thromb Haemost. 2019 Jun;17(6):852-862. doi: 10.1111/jth.14450. Epub 2019 May 13. Review.
- Kutcher ME, Redick BJ, McCreery RC, Crane IM, Greenberg MD, Cachola LM, Nelson MF, Cohen MJ. Characterization of platelet dysfunction after trauma. J Trauma Acute Care Surg. 2012 Jul;73(1):13-9. doi: 10.1097/TA.0b013e318256deab.
- Moore EE, Moore HB, Kornblith LZ, Neal MD, Hoffman M, Mutch NJ, Schöchl H, Hunt BJ, Sauaia A. Trauma-induced coagulopathy. Nat Rev Dis Primers. 2021 Apr 29;7(1):30. doi: 10.1038/s41572-021-00264-3. Review. Erratum in: Nat Rev Dis Primers. 2022 Apr 22;8(1):25.
- 5500/2021-SZTE