title: Transfusion of fresh murine red blood cells reverses adverse effects of older stored red blood cells.
abstract: BACKGROUND
  Although a subset of recent studies have suggested that red blood cell (RBC) storage length is associated with adverse patient outcomes, others have shown no such relationship. Adults may be transfused with RBC units of different storage lengths, and existing studies do not take into consideration that fresh RBCs may alter responses to concurrently transfused stored RBCs. To test this possibility, we utilized a murine model and investigated transfusion outcomes of fresh, stored, or fresh-plus-stored RBCs.
  
  
  METHODS
  Fresh, 14-day-stored or fresh plus 14-day-stored leukoreduced RBCs from HOD-transgenic donors (with RBC-specific expression of hen egg lysozyme, ovalbumin, and human Duffy(b)) were transfused into naïve C57BL/6 recipients. Serum cytokines and anti-HOD alloimmunization were evaluated after transfusion.
  
  
  RESULTS
  In six of six experiments (n = 90 mice total), a proinflammatory serum cytokine storm of interleukin-6, keratinocyte-derived chemokine/CXCL1, and monocyte chemoattractant protein-1 was observed in transfusion recipients of stored but not fresh RBCs, along with high degrees of anti-HOD alloimmunization. However, concurrent transfusion of fresh HOD RBCs along with stored HOD RBCs significantly decreased these adverse outcomes (p < 0.05).
  
  
  CONCLUSIONS
  These results are consistent with fresh murine HOD RBCs losing protective properties during storage, and introduce a previously unrecognized variable in RBC storage studies. If translatable to humans, uniform "old blood" groups may be needed in future clinical studies to more accurately investigate the biologic effects of older RBC units.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pathology and Laboratory Medicine, Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Hendrickson
authors.forename: Eldad A
authors.initials: EA
authors.lastname: Hod
authors.forename: Krystalyn E
authors.initials: KE
authors.lastname: Hudson
authors.forename: Steven L
authors.initials: SL
authors.lastname: Spitalnik
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
mesh_terms: D000328:Adult; D000818:Animals; D001793:Blood Preservation / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000166:cytology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors
chemical_list: D016207:Cytokines