Persistent injury-associated anemia and aging: Novel insights

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Abstract

BACKGROUND

Hypercatecholaminemia and bone marrow dysfunction have been implicated in the pathophysiology of persistent injury-associated anemia. The elderly may be more vulnerable to bone marrow dysfunction due to high basal and peak catecholamine levels and impaired hematopoietic progenitor growth. We hypothesized that aging would adversely affect persistent injury-associated anemia.

METHODS

Male Sprague-Dawley rats aged 8 to 9 weeks and F344-BN rats aged 25 months were randomized to naive controls, lung contusion plus hemorrhagic shock (LCHS), and LCHS plus daily chronic restraint stress (LCHS/CS). Urine norepinephrine was measured on Days 1 and 7. Mobilization of hematopoietic progenitor cells (HPCs), bone marrow colony-forming units–erythroid growth, and peripheral blood hemoglobin, mean corpuscular volume (MCV), and red cell distribution width (RDW) were assessed on Day 7 (*p < 0.05 young vs. aged counterpart by one-way analysis of variance).

RESULTS

Aged rats had higher norepinephrine levels at naive baseline (97* vs. 27 ng/mL) and 7 days following LCHS/CS when compared with young (359* vs. 127 ng/mL). Following LCHS/CS, HPC mobilization was greater among young rats when compared with aged (5.4 vs. 2.5%). Colony-forming units–erythroid growth was lower among aged animals for each group (naive: 47* vs. 65; LCHS: 40* vs. 50; LCHS/CS: 38* vs. 44 cells/plate). Aged naive rats had higher initial hemoglobin (15.2* vs. 14.3 g/dL) but lower MCV (48* vs. 59 fL/cell) and larger RDW at baseline and greater differences 7 days after LCHS/CS (MCV: 46* vs. 60 fL/cell; RDW: 17.4* vs. 16.3%).

CONCLUSIONS

Compared with young rats, aged rats had less HPC mobilization despite elevated basal and peak norepinephrine. Aged rats were disproportionately affected by impaired hematopoietic progenitor growth and an iron-restricted red blood cell phenotype at baseline, which persisted 7 days after injury. Further research is needed to assess how the clinical approach to persistent injury-associated anemia should differ for elderly trauma patients.

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