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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
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Viscoelastic assays and aggregometry tests | Diagnostic Test | Viscoelastic assays and aggregometry tests performed with ROTEM will allow us to characterize the clot forming abilities and platelet functions of our patients. ROTEM is used routinely for aiding clinicians in choosing the appropriate blood products for patients ROTEM requires samples of whole blood in an amount that does not entail additional burden or risk for patients. In our study, viscoelastic assays and aggregometry will be performed upon arrival, and 24-,48-,72-hours post-admission. |
| Measure | Description | Time Frame |
|---|---|---|
| Association between mitochondrial functions and aggregation capacity of platelets | 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. | 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Association between platelet mitochondrial functions and clot formation ability | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Severely injured trauma patients with hemorrhage
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Petra Dr. Hartmann, MD, Ph.D. | Contact | +36304388695 | petra.hartmann@med.u-szeged.hu | |
| Péter Dr. Jávor, M.D. | Contact | +36703193420 | peter.javor.md.@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Endre Prof. Dr. Varga, M.D,Ph.D,DSc | Department of Traumatology, University of Szeged | Study Director |
| Petra Dr. Hartmann, M.D., Ph.D. | Department of Traumatology, University of Szeged | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Traumatology, University of Szeged | Szeged | 6720 | Hungary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33927200 | Background | Moore EE, Moore HB, Kornblith LZ, Neal MD, Hoffman M, Mutch NJ, Schochl 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. | |
| 22308457 | Background | 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. |
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| ID | Term |
|---|---|
| D001778 | Blood Coagulation Disorders |
| D014947 | Wounds and Injuries |
| D006470 | Hemorrhage |
| D001791 | Blood Platelet Disorders |
| D020141 | Hemostatic Disorders |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| 72 hours |
| Association between platelet mitochondrial functions and conventional laboratory markers of hemostasis | 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. | 72 hours |
| Relation between platelet mitochondrial functions and mortality | 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. | 72 hours |
| 30985957 | Background | 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. |
| 22743367 | Background | 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. |
| 34954696 | Derived | Javor P, Rarosi F, Horvath T, Torok L, Hartmann P. Mitochondrial Dysfunction in Trauma-Related Coagulopathy: Is There Causality? Study Protocol for a Prospective Observational Study. Eur Surg Res. 2023;64(2):304-309. doi: 10.1159/000521670. Epub 2021 Dec 24. |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006474 | Hemorrhagic Disorders |