On the source of the non-transferrin-bound iron which accumulates in packed red blood cell units during storage

Background. Recent studies have shown large increases in non-transferrin-bound iron (NTBI) and biomarkers of oxidative stress in the extracellular medium of packed red blood cell units during storage. It has been further suggested that transfusion-mediated iron and oxidative load may contribute to transfusion-related morbidity in premature babies. The origin and nature of the NTBI is currently unclear, but the release of iron from oxidatively modified haemoglobin and haem has been suggested. The purpose of this study was to investigate whether this may be the case. Materials and methods. The concentration of haem in the extracellular fluid of paediatric packed cell units stored from 3 to 35 days was measured using a commercial haem assay. In vitro studies were conducted using haem (haemin; ferriprotoporphyrin IX chloride) to determine whether the NTBI assay was able to react with and measure iron associated with haem in the presence and absence of oxidising agents. Results. The level of haem in the extracellular fluid of paediatric packed cell units rose gradually from day 3 to day 21, then more rapidly to day 35. Very little NTBI was released from haem in the absence of oxidising agents, but the amount rose in a dose- and time-dependent manner in proportion to the oxidation of haem by incubation with H2O2. Discussion. The results of the study imply that the NTBI measured in previous studies may derive from the oxidatively modified haem that builds up in the extracellular fluid of packed red blood cell units during storage. The potential influence of this on transfusion mediated morbidity is discussed.