Omics markers of platelet transfusion in trauma patients

Abstract

BackgroundEven in the era of the COVID‐19 pandemic, trauma remains the global leading cause of mortality under the age of 49. Trauma‐induced coagulopathy is a leading driver of early mortality in critically ill patients, and transfusion of platelet products is a life‐saving intervention to restore hemostasis in the bleeding patient. However, despite extensive functional studies based on viscoelastic assays, limited information is available about the impact of platelet transfusion on the circulating molecular signatures in trauma patients receiving platelet transfusion.Materials and MethodsTo bridge this gap, we leveraged metabolomics and proteomics approaches to characterize longitudinal plasma samples (n = 118; up to 11 time points; total samples: 759) from trauma patients enrolled in the Control Of Major Bleeding After Trauma (COMBAT) study. Samples were collected in the field, in the emergency department (ED), and at intervals up to 168 h (7 days) post‐hospitalization. Transfusion of platelet (PLT) products was performed (n = 30; total samples: 250) in the ED through 24 h post‐hospitalization. Longitudinal plasma samples were subjected to mass spectrometry‐based metabolomics and proteomics workflows. Multivariate analyses were performed to determine omics markers of transfusion of one, two, three, or more PLT transfusions.ResultsHigher levels of tranexamic acid (TXA), inflammatory proteins, carnitines, and polyamines were detected in patients requiring PLT transfusion. Correlation of PLT units with omics data suggested sicker patients required more units and partially overlap with the population requiring transfusion of packed red blood cell products. Furthermore, platelet activation was likely increased in the most severely injured patients. Fatty acid levels were significantly lower in PLT transfusion recipients (at time of maximal transfusion: Hour 4) compared with non‐recipients, while carnitine levels were significantly higher. Fatty acid levels restore later in the time course (e.g., post‐PLT transfusion).DiscussionThe present study provides the first multi‐omics characterization of platelet transfusion efficacy in a clinically relevant cohort of trauma patients. Physiological alterations following transfusion were detected, highlighting the efficacy of mass spectrometry‐based omics techniques to improve personalized transfusion medicine. More specialized clinical research studies focused on PLT transfusion, including organized pre and post transfusion sample collection and limitation to PLT products only, are required to fully understand subsequent metabolomic and proteomic alterations.

Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

“…To investigate molecular signature similarities between swine and human, multiomics data from the COMBAT clinical study were leveraged. Comparison of swine ( n = 24) using EOS samples and severe multisystem injured patients ( n = 7) using emergency department [ED, median ambulance ride of 29 min (IQR 22–32)] samples showed an overlap of 462 protein and 53 metabolite identifications (Figure A).…”

“…Multiomics data were selected from a subgroup of patients from the control of major bleeding after trauma (COMBAT) cohort that represented severe multisystem injury (median base excess −13 and median NISS = 50) and TBI. These multiomics data were acquired from plasma samples processed and analyzed by MS in our laboratory using the same protocols as described for swine in this study.…”