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.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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 uncrossmatched RBC substitution.
Bogner
Viktoria
V
Chirurgische Klinik und Poliklinik-Innenstadt, Ludwig-Maximilians University, Munich, Munich, Germany. Viktoria.Bogner@med.uni-muenchen.de
Baker
Henry V
HV
Kanz
Karl-Georg
KG
Moldawer
L L
LL
Mutschler
Wolf
W
Biberthaler
Peter
P
D000328:Adult; D017707:Erythrocyte Transfusion; D005260:Female; D015894:Genome, Human; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000235:genetics; D009104:Multiple Trauma / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D025822:Ubiquitin C / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014949:Wounds, Nonpenetrating / Q000235:genetics*; D055815:Young Adult
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D025822:Ubiquitin C; D000072000:NF-KappaB Inhibitor alpha