Biopreservation of red blood cells--the struggle with hemoglobin oxidation

One of the least recognized causes of cellular damage during ex vivo preservation of red blood cells is oxidative injury to the hemoglobin. The latter has been associated with hemolysis through the release of toxic substances and oxidation of vital cell components. This review delineates some of the major pathways that link hemoglobin oxidation and cellular damage, and summarizes the incidence of red blood cell oxidative injury during hypothermic storage, cryopreservation and desiccation stress. Red blood cell hypothermic storage, despite its success, is not exempt from oxidative injury. Growing evidence portrays a time-dependant oxidative assault including formation of reactive oxygen species, attachment of denatured hemoglobin to membrane phospholipids and the release of hemoglobin-containing membrane microvesicles throughout storage. Similar symptoms have been observed in attempts to stabilize red blood cells in the dried state, in which methemoglobin levels of reconstituted red blood cells reached 50%. Factors affecting the rate of hemoglobin oxidation during red blood cell ex vivo storage include compromised antioxidant activity, high concentrations of glucose in the storage media and the presence of molecular oxygen. Hemoglobin oxidation largely dictates our ability to effectively preserve red blood cells. Understanding its origins along with investigating methods to minimize it can significantly improve the quality of our future blood products.