Sanne de Bruin

145 Storage of RBCs in PAGGGM improves metabolism after transfusion but has no effect on PTR Introduction Directly after red blood cell (RBC) transfusion, a significant number of RBCs is cleared from the circulation 1,2 . Several studies have reported that post-transfusion recovery (PTR), i.e. the percentage of RBCs that circulate at 24h after transfusion, is heteroge- neous across the donor population, with units showing poor PTR (<75%) below Food and Drug Administration and European Council thresholds 3 . In some patients up to 38% of the transfused RBCs is cleared in the first 24 hours 1,2 . Similar observations on the heterogeneity of PTR as a function of genetic make-up of the donors have been reca- pitulated inmechanistic studies in rodents models showing an impact of iron and redox metabolism on PTR 4 . A low PTR might result in a larger need of blood products as well as a more frequent exposure to the potential harmful side effects of RBC transfusion 5,6 . RBC storage time is one of the factors associated with a decreased PTR 1 . During storage RBCs undergo several metabolic and morphological changes, known as the “storage lesion”. The metabolic changes include decreased cellular levels of 2,3-diphosphoglyc- erate(2,3-DPG), adenosine triphosphate (ATP) and an impaired redox metabolism 7–11 . Decrease of the intracellular pH contributes significantly to the storage lesion. The rate limiting enzyme of glycolysis, phosphofructokinase (PFK), is inhibited at pH < 7.0 12 . The additive solutions that are used to preserve RBCs is another important factor in main- taining RBC integrity during storage. However, both citrate-phosphate-dextrose (CPD, anticoagulant), as well as the standard additive solution for storage of RBCs in Europe (saline-adenine-glucose-mannitol (SAGM)), have a pH of 5-6, resulting in a relatively low pH for the RBC concentrate. The low pH of the additive is readily buffered by RBC incubation to the solution during processing of the unit. However, the intracellular pH progressively acidifies during storage as a function of lactate formation from ongoing glycolysis. It is unclear to what extent these metabolic changes are reversible. ATP and 2,3-DPG levels can restore within 72 hours after transfusion 13–15 . However, storage also impacts the main antioxidant pathways 16 (e.g., the pentose phosphate pathway – PPP and glu- tathione - GSHmetabolism), purine 16 and lipid oxidation 17 . It is unknown whether these metabolic lesions also improve after transfusion. Reduction of storage time or improvement of additive solutions may result in increased RBC quality and PTR. Several studies have shown better preservation of glycolysis ac- tivity and redox metabolism using alkaline, chloride free additive solutions 18,19 . Storage 6