Blood Journal
Leading the way in experimental and clinical research in hematology

Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation

  1. Eldad A. Hod1,*,
  2. Ning Zhang2,
  3. Set A. Sokol1,
  4. Boguslaw S. Wojczyk1,
  5. Richard O. Francis1,
  6. Daniel Ansaldi2,
  7. Kevin P. Francis2,
  8. Phyllis Della-Latta1,
  9. Susan Whittier1,
  10. Sujit Sheth3,
  11. Jeanne E. Hendrickson4,
  12. James C. Zimring5,
  13. Gary M. Brittenham3, and
  14. Steven L. Spitalnik1
  1. 1 Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, United States;
  2. 2 Caliper Life Sciences, Alameda, CA, United States;
  3. 3 Departments of Pediatrics and Medicine, Columbia University College of Physicians and Surgeons, New York, NY, United States;
  4. 4 AFLAC Cancer Center and Blood Disorders Service, Emory University School of Medicine, Atlanta, GA, United States;
  5. 5 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States
  1. * Corresponding author; email: eh2217{at}


Although red blood cell (RBC) transfusions can be lifesaving, they are not without risk. In critically ill patients, RBC transfusions are associated with increased morbidity and mortality, which may increase with prolonged RBC storage before transfusion. The mechanisms responsible remain unknown. We hypothesized that acute clearance of a subset of damaged, stored RBCs delivers large amounts of iron to the monocyte/macrophage system, inducing inflammation. To test this in a well-controlled setting, we used a murine RBC storage and transfusion model to show that the transfusion of stored RBCs, or washed stored RBCs, increases plasma non-transferrin bound iron (NTBI), produces acute tissue iron deposition, and initiates inflammation. In contrast, the transfusion of fresh RBCs, or the infusion of stored RBC-derived supernatant, ghosts, or stroma-free lysate, does not produce these effects. Furthermore, the insult induced by stored RBC transfusions synergizes with sub-clinical endotoxinemia producing clinically overt signs and symptoms. The increased plasma NTBI also enhances bacterial growth in vitro. Taken together, these results suggest that, in a mouse model, the cellular component of leukoreduced, stored RBC units contributes to the harmful effects of RBC transfusion that occur after prolonged storage. Nonetheless, these findings must be confirmed by prospective human studies.

  • Submitted October 9, 2009.
  • Accepted March 4, 2010.