Mitochondrial Dysfunction in Trauma-related Coagulopathy

NCT05004844 | Unknown

• 1 other identifier: 5500/2021-SZTE
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Trauma Induced Coagulopathy

Keywords

blood coagulation disorders; wounds and injuries; hemorrhage; mitochondria; blood platelet disorders; thrombelastography; coagulopathy, trauma induced

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Association between platelet mitochondrial functions and clot formation ability

  72 hours

• Association between platelet mitochondrial functions and conventional laboratory markers of hemostasis

  72 hours

• Relation between platelet mitochondrial functions and mortality

  72 hours

Interventions

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Severely injured trauma patients with hemorrhage

You may qualify if:

• 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)

Sponsors & Collaborators

• Petra Hartmann MD Ph.D.: lead

Study Sites (1)

Department of Traumatology, University of Szeged

Szeged, 6720, Hungary

Location

Related Publications (5)

• 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.

  PMID: 33927200 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.

  PMID: 22308457 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.

  PMID: 30985957 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.

  PMID: 22743367 BACKGROUND

• 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.

  PMID: 34954696 DERIVED

MeSH Terms

Conditions

Blood Coagulation Disorders; Wounds and Injuries; Hemorrhage; Blood Platelet Disorders; Hemostatic Disorders

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders

Study Officials

• 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

Central Study Contacts

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 13, 2021
• Study Start: October 31, 2021
• Primary Completion: October 31, 2022
• Study Completion: January 31, 2023
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)