Hemoglobin Oxidation Reactions in Stored Blood

Hemoglobin (Hb) inside and outside the red blood cells (RBCs) undergoes constant transformation to an oxidized form in a process known as autoxidation. The ferrous heme iron (Fe2+) of the prosthetic group is spontaneously transformed into an oxidized ferric (Fe3+) form, but under oxidative stress conditions a higher oxidation ferryl heme (Fe4+) is also formed. Although Fe3+ is a non-functional form of Hb, the Fe4+ is also extremely reactive towards other biological molecules due to its high redox potential. The RBC contains an effective reductive machinery that maintains Hb in the functional form with little oxidation during its life span. The redox transformation of Hb occurs to a lesser extent in young RBCs; it may, however, have detrimental effects on the integrity of these cells during ex vivo storage or when RBCs are subjected to pathogen reduction processes. In this review, Hb oxidation reactions ("oxidative lesion") will be described, including details of how these reactions might impact the clinical use of stored or processed blood for therapeutic purposes.