Mitochondrial Dysfunction in Trauma-Related Coagulopathy: Is There Causality? Study Protocol for a Prospective...

Area of Science:

• Mitochondrial biology
• Trauma and critical care medicine
• Hematology

Background:

• Trauma-induced coagulopathy (TIC) complicates hemorrhage control, with platelet dysfunction playing a key role.
• Mitochondrial activity is crucial for platelet activation and clot formation, suggesting their involvement in TIC pathogenesis.
• Current understanding of mitochondrial derangements in TIC remains incomplete.

Purpose of the Study:

• To quantitatively assess mitochondrial function in platelets of severely injured trauma patients.
• To explore the association between platelet mitochondrial function and hemostasis markers.
• To investigate the link between platelet mitochondrial function and clinical outcomes like massive transfusion and mortality.

Main Methods:

• Prospective observational study of 111 severely injured trauma patients (ISS ≥16).
• Exclusion of patients on oral antiplatelet agents.
• Assessment of platelet mitochondrial respiration using high-resolution fluororespirometry, measuring oxidative phosphorylation, electron transport chain coupling, and superoxide formation.
• Correlation with conventional hemostasis markers and rotational thromboelastometry (ROTEM).

Main Results:

• Platelet mitochondrial respiration (OxPhos capacity) was quantitatively characterized.
• Associations were examined between OxPhos capacity and ROTEM parameters, conventional hemostasis markers, need for massive transfusion, and 24-h mortality.
• Primary outcome: association between OxPhos capacity and ROTEM aggregometry parameters.

Conclusions:

• Mitochondrial dysfunction in platelets is implicated in trauma-induced coagulopathy.
• Quantifying platelet mitochondrial function may offer insights into TIC.
• Identifying mitochondria-mediated processes in platelets could lead to novel therapeutic strategies for managing hemorrhage in trauma patients.