Mitochondrial Dysfunction in Trauma-related Coagulopathy

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Trauma Induced Coagulopathy

Intervention / Treatment
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* Diagnostic Test: Viscoelastic assays and aggregometry tests


Participation Criteria
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Eligibility Criteria
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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: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Viscoelastic assays and aggregometry tests|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.|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood coagulation disorders, wounds and injuries, hemorrhage, mitochondria, blood platelet disorders, thrombelastography, coagulopathy, trauma induced