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

Blood - Tập 115 Số 21 - Trang 4284-4292 - 2010
Eldad A. Hod1,2, Ning Zhang3, Set Sokol1, Bogusław S. Wójczyk1, Richard O. Francis1, Daniel Ansaldi3, Kevin P. Francis3, Phyllis Della‐Latta1, Susan Whittier1, Sujit Sheth4, Jeanne E. Hendrickson5,6, James C. Zimring6, Gary M. Brittenham4, Steven L. Spitalnik1
1Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY
2New York Blood Center, NY
3Caliper Life Sciences, Alameda, CA;
4Departments of Pediatrics and Medicine, Columbia University College of Physicians and Surgeons, New York, NY;
5AFLAC Cancer Center and Blood Disorders Service, Emory University School of Medicine, Atlanta, GA; and
6Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.

Tóm tắt

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 nontransferrin 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 transfusion of stored RBC synergizes with subclinical 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.

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Blood

Tập 115 Số 21

4284-4292

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