Sanne de Bruin

125 Metabolic changes in erythrocytes in vivo, during storage and after transfusion Introduction Red blood cell (RCC) transfusion is themost widely applied cellular therapy inmedicine. To guarantee the supply of blood products it is inevitable to store red blood cells for a certain time. Storage of RCCs up to 49 days is allowed, depending on local regulations. The alterations which occur during storage are well studied and are known as the stor- age leasion 1,2 . These alterations include morphological and biochemical changes of which some are reversible, depending on the duration of storage 3 . The current opinion is that certain biochemical compounds are important for survival and functionality of erythrocytes like adenosine triphosphate (ATP), 2,3-diphosphoglyc- erate (2,3-DPG) and glutathione (GSH). The importance of these metabolites in vivo is seen in red blood cell disorders caused by deficiencies in enzymes that generate these compounds. For example, erythrocytes from patients suffering from glucose-6-phos- phate-dehydrogenase (G6PD) deficiency contain lower GSH levels resulting in haemo- lysis when erythrocytes are exposed to oxidative stress 4 . Furthermore, a defect in one of the enzymes catalysing a step in the glycolysis, such as in pyruvate kinase and hex- okinase deficiency, resulting in decreased ATP levels, leads to constant mild to severe haemolytic anemia 5 . Finally, 2,3-DPG levels are important for the correct oxygen carry- ing function of erythrocytes. Low 2,3-DPG levels result in increased oxygen affinity of haemoglobin leading to decreased oxygen offload to the peripheral tissue 6 . Thus low 2,3-DPG levels lead to impaired oxygen transport of erythrocytes to the tissues. This is exemplified in patients suffering from2,3-DPGmutase deficiency, which results in lower 2,3-DPG levels and a compensatory polycythemia 7 . Over the years multiple research groups have studied the metabolic changes during in vivo and in vitro aging of erythrocytes. Significant differences exist in different metabolic pathways comparing in vivo aging with in vitro aging. These insights have helped blood banks to improve storage conditions over the years, and thereby improving the quality of stored blood products. In the previous century metabolic changes in erythrocytes during in vivo an in vitro aging have been well studied. These studies were, however, mainly focused on a limit- ed number of metabolites or enzymes which could lead to certain biases. The last two decades the scientific field studying this subject has advanced rapidly. Nowadays it is possible to measure a broad spectrum of metabolites and proteins at once using mass spectrometry approaches. These new approaches make it possible to do untargeted 5