Mitochondrial Dysfunction in Trauma-related Coagulopathy

Mitochondrial Dysfunction in Trauma-related Coagulopathy - Is There Causality? - Study Protocol for a Prospective Observational Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Trauma Induced Coagulopathy
• Intervention / Treatment: Diagnostic test: Viscoelastic assays and aggregometry tests

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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Petra Dr. Hartmann, MD, Ph.D.; Phone Number: +36304388695; Email: petra.hartmann@med.u-szeged.hu
• Study Contact Backup: Name: Péter Dr. Jávor, M.D.; Phone Number: +36703193420; Email: peter.javor.md.@gmail.com

Study Locations

• Hungary
  • Szeged, Hungary, 6720
    • Department of Traumatology, University of Szeged
    • Contact: Eszter Bucsuházy; Phone Number: +3662545531; Email: office.trauma@med.u-szeged.hu
    • Principal Investigator: Petra Hartmann, MD, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Severely injured trauma patients with hemorrhage

Description

Inclusion Criteria:

• Trauma patients
• Injury Severity Score (ISS) 16 or greater,
• age of 18 years or greater,
• hemorrhage confirmed with extended focused assessment with sonography in trauma (eFAST) or computer tomography (CT)

Exclusion Criteria:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• 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. Erratum In: Nat Rev Dis Primers. 2022 Apr 22;8(1):25.
• 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.
• 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.
• 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. 2021 Dec 24;63(4):192-7. doi: 10.1159/000521670. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 31, 2021
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: mitochondria; hemorrhage; wounds and injuries; blood coagulation disorders; thrombelastography; blood platelet disorders; coagulopathy, trauma induced
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Wounds and Injuries
• Other Study ID Numbers: 5500/2021-SZTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No