The authors have previously published a murine model with preclinical data to support their hypothesis that acute delivery of hemoglobin iron to the monocyte-macrophage system by transfusion and phagocytosis of older, stored red blood cells are inflammatory and immunosuppressive. The authors propose a clinical trial in humans to test this “iron hypothesis” in which normal volunteers will each be transfused with a “fresh” (3-7 days storage) autologous unit and an older (40-42 days storage) autologous unit; the primary outcomes will be laboratory iron parameters and assays for pro-inflammatory cytokines. Similar studies are planned for transfusion of allogeneic red blood cells to chronically transfused patients with hemoglobinopathies. The goal of each clinical study is to determine the mechanism(s) for the potential storage lesion mediated by hemoglobin iron.

– Lawrence Tim Goodnough