A New Trauma Frontier: Exploratory Pilot Study of Platelet Transcriptomics in Trauma Patients.
2021
BACKGROUND The earliest measurable changes to post-injury platelet biology may be in the platelet transcriptome, as platelets are known to carry messenger ribonucleic acids (RNAs), and there is evidence in other inflammatory and infectious disease states of differential and alternative platelet RNA splicing in response to changing physiology. Thus, the aim of this exploratory pilot study was to examine the platelet transcriptome and platelet RNA splicing signatures in trauma patients compared to healthy donors. METHODS Pre-resuscitation platelets purified from trauma patients (n = 9) and healthy donors (n = 5) were assayed using deep RNA sequencing. Differential gene expression analysis, weighted gene co-expression network analysis, and differential alternative splicing analyses were performed. In parallel samples, platelet function was measured with platelet aggregometry, and clot formation was measured with thromboelastography. RESULTS Differential gene expression analysis identified 49 platelet RNAs to have differing abundance between trauma patients and healthy donors. Weighted gene co-expression network analysis identified co-expressed platelet RNAs that correlated with platelet aggregation. Differential alternative splicing analyses revealed 1188 splicing events across 462 platelet RNAs that were highly statistically significant (false discovery rate < 0.001) in trauma patients compared to healthy donors. Unsupervised principal component analysis of these platelet RNA splicing signatures segregated trauma patients in two main clusters separate from healthy controls. CONCLUSIONS Our findings provide evidence of finetuning of the platelet transcriptome through differential alternative splicing of platelet RNA in trauma patients, and that this finetuning may have relevance to downstream platelet signaling. Additional investigations of the trauma platelet transcriptome should be pursued to improve our understanding of the platelet functional responses to trauma on a molecular level.Study typeBasic Science. LEVEL OF EVIDENCE N/A.
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