Harmful effects of transfusion of older stored red blood cells: iron and inflammation.

Retrospective studies suggest that the transfusion of older, stored red blood cells (RBCs) may be associated with increases in mortality, serious infections, multiorgan failure, thrombosis, and hospital length of stay. Our research is based on the overarching hypothesis that the adverse effects associated with transfusion of older, stored RBCs result from the acute delivery of hemoglobin iron to the monocyte-macrophage system. To test this "iron hypothesis," we are recruiting healthy human volunteers to donate double, leukoreduced, RBC units. We then transfuse them with one autologous fresh unit (i.e., after 3-7 days of storage) and one older, stored unit (i.e., at 40-42 days of storage). The primary study outcome will compare laboratory iron measures and proinflammatory cytokines after transfusion of fresh or older, stored RBCs. Similar studies using allogeneic RBC transfusions will be performed in chronically transfused patients with either sickle cell disease or β-thalassemia. Although prospective, randomized studies will ultimately determine the existence of adverse effects from transfusing older, stored RBCs, our goal is to determine the mechanism(s) for this potential effect.