Iron homeostasis

Transfusions are often lifesaving but they also carry risks for transfusion-related complications, including iron accumulation. Although transfusion of a RBC unit is a safe, often life-saving therapy, a substantial percentage (10-25%) of the transfused RBC are degraded within 24hrs after the transfusion. This loss of donor RBC is the result of the detrimental changes that occur in the RBC during cold storage, and as each RBC unit contains 250 mg of iron, this means a patient receives 25 to 62.5 mg of iron that needs to be recycled in the first 24 hrs after transfusion. Since the human body has no regulatory mechanism to excrete the excess iron delivered to the body by transfusion, chronic blood transfusions result in high circulating iron levels and tissue iron overload. Also, many patients who receive RBCs have ineffective erythropoiesis that is associated with higher iron uptake from the diet and iron redistribution from the reticuloendothelial system to the parenchymal cells and as such contributes to toxic body iron overload. If untreated this transfusion related iron overload leads to irreversible organ injury and causes considerable morbidity, such as heart failure, liver cirrhosis, growth retardation, and diabetes, ultimately resulting in death. The underlying mechanism(s) leading to tissue toxicity of iron overload are still mostly unknown.
On the other hand, in some circumstances, iron intake is inadequate to compensate for physiological or pathological losses, leading to depletion of body iron stores. For instance, by withdrawing blood from blood donors, vast amounts of iron are being transferred from donor to patient. As a result, donors may be deprived of iron due to frequent donations, ultimately leading to iron deficiency and anemia and causing whole blood donor deferral.
Our research focusses on the understanding of (cell specific) pathways leading to iron overload toxicity after RBC transfusions, and the identification of novel genetic variants for the prediction of iron deficiency and/or anemia in donors.