Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient

Abstract

The putative ‘red blood cell (RBC) hypothermic storage lesion’ is the focus of intense interest and investigation in transfusion medicine . Owing to detrimental changes taking place during a period of up to 42 days, the RBC ability to sustain normal functionality after transfusion can become compromised. While our understanding of the RBC storage lesion has been advanced by a myriad of historical and more recent studies1-10, the clinical significance of transfusing “old blood” remains unclear. In this issue of Transfusion, Yu et al11, discuss the possible outcomes of transfusing stored versus fresh mouse RBCs into syngeneic susceptible hosts, that is mice with diabetes. They demonstrate that transfusion of stored RBCs or supernatants from stored RBCs can induce systemic hypertension and vasoconstriction in mice suffering endothelial dysfunction (diabetic mice), and that transfusion-induced vasoconstriction can be prevented by nitric oxide (NO) inhalation or oxidation of supernatants from stored RBCs. They correlate the hypertensive effects with hemolysis of stored RBCs and NO scavenging by cell-free hemoglobin. Yu and colleagues’ study supports recent mechanisms for the putative RBC storage lesion related to red cell hemolysis and inactivation of endothelial nitric oxide1,3,12,13 that may in part contribute to transfusion-related multi-organ injury, particularly in the setting of massive transfusion. Their work highlights the interaction between the age of banked blood and the health of the blood recipient (susceptible host), as well as characterizes the potential therapeutic use of NO to ameliorate severe outcomes in patients suffering from endothelial dysfunction caused by transfused blood hemolysis.