The Postinjury Inflammatory State and the Bone Marrow Response to Anemia

Abstract

Severe blunt trauma was associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, erythroid progenitor growth suppression, and persistent injury-associated anemia. Clinical trial registered with www.clinicaltrials.gov (NCT 02577731).

Impact of Injury Severity on the Inflammatory State and Severe Anemia

“…Yet, bone marrow expression of TfR-1 was decreased following severe trauma, representing the rate-limiting component of iron uptake by erythroid progenitors. 27,35 Loftus et al 27 postulated that for iron homeostasis and normal erythropoiesis, iron bioavailability must be accompanied by iron uptake in erythroid progenitors, which is facilitated by transferrin and its receptor via receptor-mediated endocytosis. Our findings in this study are consistent with the iron homeostasis process following trauma being interrupted both by decreased iron bioavailability due to an increase in hepcidin concentration as well as a decrease in transferrin receptor expression preventing iron uptake by the erythroid progenitors.…”

“…[11][12][13][21][22][23][24][25][26] Prior research has evaluated the postinjury inflammatory state in severely injured trauma patients and demonstrated their erythropoietic dysfunction and iron dysregulation. 27 To validate our preclinical findings and to expand upon our prior study of the postinjury inflammatory state in humans, the purpose of this study was to evaluate additional severely injured trauma patients and determine if there is a relationship between the ISS in trauma patients, and the degree of neuroendocrine activation and systemic inflammation that is related with persistent injury-associated anemia as well as to further characterize the bone marrow response to injury. To compare a continuum of neuroendocrine activation, we evaluated erythropoietic function in healthy controls, elective hip replacement patients, and blunt trauma patients.…”

“…These three groups were included to compare a transient stress response (elective hip replacement) and persistent hypercatecholaminemia (severe blunt trauma) to healthy controls. As reported by Loftus et al, 27 trauma patients from a level 1 trauma center were screened on admission for inclusion in the study. This study was registered at ClinicalTrials.gov/ (NCT02577731) and approved by the University of Florida Institutional Review Board (IRB201601386).…”

“…As previously described, 27 the bone marrow samples were collected during the scheduled open reduction and internal fixation of the hip or long bone fracture for the trauma and hip replacement patients, using an 11-gauge bone marrow biopsy needle (Covidien, Minneapolis, MN) at the fracture site. An investigator (TJL, ESM, CGA, JAS) was present in the operating room for collection of all bone marrow samples, which were obtained from the sterile field by an orthopedic surgeon (JEH, HKP, KKS, MP) to ensure consistency of the sample collection.…”

“…RNA was isolated from human bone marrow and reverse transcribed to cDNA, per our standard protocol. 27 Real-time polymerase chain reaction was performed using Brilliant II SYBR Green QPCR Master Mix (Agilent Technologies, Santa Clara, CA) and the Mx3005P qPCR System (Agilent Technologies), reported as mRNA fold change relative to healthy controls. Primers were designed using Primer3 Web software.…”