Omics markers of platelet transfusion in trauma patients

医学 组学 血小板 凝血病 血小板输注 堆积红细胞 人口 输血 内科学 重症监护医学 生物信息学 生物 环境卫生
作者
Ian S. LaCroix,Mitchell J. Cohen,Ernest E. Moore,Monika Dzieciątkowska,Christopher C. Silliman,Kirk C. Hansen,Angelo D’Alessandro
出处
期刊:Transfusion [Wiley]
卷期号:63 (8): 1447-1462 被引量:2
标识
DOI:10.1111/trf.17472
摘要

Even 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.To 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.Higher 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).The 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.
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