Analysis of mitochondrial function of platelets from polytrauma patients

Abstract text (incl. references and figure legends)

Introduction:The pathogenesis of trauma-induced coagulopathy (TIC) is not yet fully understood. However, platelet activation and subsequent clot formation are linked to mitochondrial activity suggesting a possible role for mitochondria in TIC. We aimed to investigate the mitochondrial function of platelets using high-resolution respirometry in TIC. Methods: Prospective observational study (ClinicalTrials.gov NCT05004844) included severely injured (injury severity score (ISS) ≥16), bleeding patients aged ≥18 years from 1 September 2021. Baseline respiratory activity and oxidative phosphorylation capacity (OxPhos) of platelet mitochondria isolated from venous blood samples at arrival, mitochondrial electron loss (after oligomycin), and maximum respiratory capacity (after FCCP) were assessed. The values obtained were normalized to the platelet count of the sample. Our results were compared with parallel aggregometric measurements of platelets (Multiplate ADPtest). Results: Baseline mitochondrial respiratory activity of isolated platelets from polytrauma patients (n=57) did not change compared to control patients (n=48). However, OxPhos was significantly decreased compared to controls (37±52 pmol/ml/sec vs 64±18 pmol/ml/sec). Lower oxygen consumption was measured after administration of oligomycin and FCCP, suggesting increased electron loss and impaired electron transport. Platelet functional tests in the polytrauma patients were all below the values of the control group, demonstrating severe coagulation disturbance (ADPtest: 112±14 AUC vs 85±69 AUC). Conclusions: Our results confirm the development of TIC in polytraumatized injured patients. ADP-induced platelet activation is perturbed, with concomitant detection of platelet mitochondrial dysfunction, including OxPhos required for platelet activation. A deeper understanding of maladaptive platelet responses after injury may provide a basis for the exploration of new therapeutic targets in polytrauma care.

Disclosure: Do you have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstract? (If not, please enter "No" in the text field.)

No