Hemorrhage and Subsequent Allogenic Red Blood Cell Transfusion are Associated With Characteristic Monocyte Messenger RNA Expression Patterns in Patients After Multiple Injury—A Genome Wide View

Abstract

Introduction As outcome to severe trauma is frequently affected by massive blood loss and consecutive hemorrhagic shock, replacement of red blood cell (RBC) units remains indispensable. Administration of RBC units is an independent risk factor for adverse outcome in patients with trauma. The impact of massive blood transfusion or uncrossmatched blood transfusion on the patients’ immune response in the early posttraumatic period remains unclear. Material Thirteen patients presenting with blunt multiple injuries (Injury Severity Score >16) were studied. Monocytes were obtained on admission and at 6, 12, 24, 48, and 72 hours after trauma. Biotinylated complementary RNA targets were hybridized to Affymetrix HG U 133A microarrays. The data were analyzed by a supervised analysis based on whether the patients received massive blood transfusions, and then subsequently, by hierarchical clustering, and by Ingenuity pathway analysis. Results Supervised analysis identified 224 probe sets to be differentially expressed (p < 0.001) in patients who received massive blood transfusion, when compared with those who did not. In addition, 331 probe sets were found differentially expressed (p < 0.001) in patients who received uncrossmatched RBC units in comparison with those who exclusively gained crossmatched ones. Functional pathway analysis of the respectively identified gene expression profiles suggests a contributory role by the AKT/PI3Kinase pathway, the mitogen-activated protein-kinase pathway, the Ubiquitin pathway, and the diverse inflammatory networks. Conclusion We exhibited for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns in patients with multiple trauma indicating a strongly significant association between the patients’ genomic response in blood monocytes and massive or uncross-matched RBC substitution.

Critical illness is an iatrogenic disorder

“…Transfusion is a potent stimulus for inflammatory gene expression after trauma (73,74). The administration of fresh-frozen plasma has also been linked to ARDS and an increased risk of organ dysfunction (75).…”

The Glue Grant experience: characterizing the post injury genomic response

“…Attempts by other groups are also ongoing to associate clinical outcomes with specific gene signatures. For example, Biberthaler et al have examined the genomic profiles of monocytes from patients post traumatic injury and have identified some association between clinical parameters and canonical signaling pathways, such as multisystem organ failure with cellular development, cell death, and ephrin signaling pathways [39–41]. However, much more work needs to be done in order to prospectively validate and to further understand what the biological implications of these genomic findings are and whether they can be used as a prognostic signature for poor outcome in these severely injured patients.…”