C. G. Apple1, E. S. Miller1, J. A. Stortz1, J. C. Mira1, M. K. Hollen1, T. J. Loftus1, M. Lopez1, Z. Wang1, K. B. Kannan1, D. C. Nacionales1, C. R. Cogle1, H. K. Parvataneni1, K. K. Sadasivan1, M. Patrick1, J. E. Hagen1, S. Brakenridge1, F. A. Moore1, H. V. Baker1, L. L. Moldawer1, P. A. Efron1, A. M. Mohr1 1University of Florida,Department Of Surgery,Gainesville, FL, USA
Introduction: Previous data has shown that severe traumatic injury is associated with bone marrow dysfunction which manifests as persistent injury-associated anemia. MicroRNAs (miR) have been emerging as critical regulators of hematopoieisis, and several miRs have been specifically linked to the regulation of erythropoiesis. We sought to identify whether the expression of any erythropoiesis-related miRs was altered in trauma patients to determine if these miRs play a role in persistent injury-associated anemia.
Methods: Bone marrow (BM) was collected intraoperatively from severely injured trauma patients [ISS≥15 or hemorrhagic shock (lactate≥2, base deficit≥5, MAP≤65)] who underwent fracture fixation as well as age-matched controls. There were 27 trauma patients and 16 controls analyzed. Total RNA & miR were isolated from CD34 positive cells using the RNeasy Plus Mini kit, and genome-wide and miR expression patterns were calculated with a log2 transformed expression matrix using RMA. Genes with significant expression differences (fold expression changes over age-matched control) were found using BRB Array Tool (p<0.001, t-test). Significance p<0.005 trauma vs controls by two-tailed unpaired t-test.
Results: There were marked differences in expression of 60 miRs in the trauma group when compared to age-matched controls when using a p<0.005. Two of these miR play a role in regulating erythropoiesis. miR 223, associated with suppression of erythrocytic differentiation, was found to be upregulated 1.9 fold in the trauma patients as compared to controls (p<0.0005). miR 150-3p, associated with diversion of stem cells towards megakaryocytes rather than erythrocyte differentiation, was found to be upregulated 1.8 fold in the trauma patients as compared to controls (p<0.0009). Hemoglobin on day of surgery was 10.2±1.89 g/dL in trauma compared to 13.8±2.31 g/dL in controls.
Conclusion: Severe blunt trauma is associated with persistent injury-associated anemia and this study identifies two miRs that were significantly upregulated in their expression when compared to age-matched controls. Further studies are needed to target these miRs and mitigate their downstream effects, thereby improving the anemia seen following severe traumatic injury.