Sanne de Bruin

216 Chapter 9 blood transfusion. A randomized controlled trial testing this hypothesis should include long-term effects such as the development of transfusion iron overload. Increased 2,3-DPG levels should theoretically result in increased oxygen offload in the peripheral tissues. It remains difficult to assess the additive value of increased 2,3-DPG levels on improving the oxygenation status in patients. Since it is not possible to mea- sure oxygen delivery of RBCs to the tissues directly in patients, we need to use surro- gate markers for tissue oxygenation. Several surrogate markers are used for research purposes including but not limited to near-infra red spectroscopy and mitochondrial oxygen content 22,23 . However, sufficient oxygen supply to the peripheral tissues is depen- dent on numerous other factors including cardiac output and arterial oxygen content. These factors are often compromised in patients, especially in those who are in need of a RBC transfusion. Possibly, a broader outcome than tissue oxygenation can be used, for instance clinical outcomes such as mortality. Finally, this study functions as proof of concept study. It is the first study that was able to isolate biotinylated RBCs after transfusion on which analysis could be performed. This method is also applicable in clinical research. Recovery of the metabolic storage lesion may be different in patients suffering from systemic illness, such as septic pa- tients. How RBCs recover in this sort of patient group might give insights on what part of the metabolism we should focus on during storage. If for instance RBCs are unable to recover their redox state in critically ill patients, it might be beneficial to preserve PPP activity, even if this is at the expense of other metabolic pathways. Platelet labelling In chapter 7 we validated a novel method to label platelets with biotin, in order to assess their PTR as well as study their phenotype after transfusion, as an alternative for labelling using radioactive isotopes. We consider biotin labelled platelets to be a good alternative for radiolabelled platelets, as these can be even administered in vulnerable patient populations. However, we found that the procedural steps in our protocol result in a small increase in platelet activation. Since labelling with radioactive isotopes in- cludes similar procedural steps platelet activation is hypothesized to be similar in label- ling with radioactive isotopes 24 . However, to our knowledge, no data has been published about the effect of radioactive isotope labelling on platelet activation. Nonetheless, the current gold standard for assessing PTR of platelets is radioactive isotope labelling. Due to strict regulations on working with radioactive material, we were unable to assess

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