Sanne de Bruin

215 General discussion Effect of an alkaline additive solution on post transfusion recovery and metabolic restoration of RBCs In chapter 6 we found that RBCs stored in an alkaline chloride-free additive solution did not have a higher post transfusion recovery (PTR) despite a better metabolic state in these RBCs. Especially the redox state and glycolysis were significantly better preserved in PAGGGM stored RBCs. This study shows that the metabolic state of RBCs is not the main driver of RBC clearance. While adenosine triphosphate (ATP) levels still might be important for the function of a RBC, wewere not able to confirm the finding of a previous study which showed a correlation between ATP levels and PTR 15 . An important limitation in assessing RBC PTR after transfusion is the lack of knowledge on the survival of the transfused RBC in the first ten minutes after transfusion. In our study, as done in most studies 15,16 , we calculated the PTR using the percentage of la- belled RBCs in the first blood sample, drawn 10 minutes after transfusion, as reference. Thus, using this method, RBC that are immediately cleared from the circulation, within the first ten minutes, are not considered. Ideally, the number of circulating RBCs and the number of administered biotinylated RBCs would be known at the time the trans- fusion was finished. Then, it would be possible to precisely calculate the PTR at any timepoint, even after tenminutes. As a surrogate, it is common practice to calculate the circulating volume of the recipient, and thereby estimate the percentage of donor RBCs as accurate as possible. However, the optimal method to assess the circulating volume in humans is by no means established. Several methods are described in literature to estimate circulating volume for clinical and research purposes, including but not limited to indocyanine green dilution and carbon mono-oxide rebreathing method 16–18 . Unfor- tunately, all these methods are estimates with different accuracies. For the purpose of determining RBC PTR, a method that allows an accurate estimation of the circulating volume is necessary. Future directives The implications of a higher PTR of fresh RBCs for clinical practice should be further in- vestigated. It is not feasible to transfuse everyone with the freshest RBCs. Furthermore, in critically ill patients it is shown that transfusion of fresh RBCs did not result in im- proved clinical outcomes compared to longer stored RBCs 19–21 . Nonetheless, theremight be specific patient populations that could benefit from an increased PTR. We postulate that patients with a chronic need for transfusion are a potential patient population that could benefit from fresh RBCs. A higher PTR could result in an increased interval between blood transfusion and thereby minimizing the long-term adverse effects of 9