Sanne de Bruin

217 General discussion platelet activation of radioactive isotope labelled platelets. However, 111-In-oxine and biotin labelled platelets have a similar lifespan after transfusion in baboons 25 . These data support our assumption that platelet activation is similar between both labelling techniques. An alternative technique that does not involve platelet manipulation prior to transfu- sion is using human leukocyte antigen (HLA) discrepancy. Here, the differences in HLA type between the donor and the recipient are used to distinguish donor from recipient PLTs. This method has several other limitations: 1) the majority of the transfused blood products are pooled products with five different donors and thus five different HLA patterns 2) when multiple platelet concentrates are administered within 10 days, it is difficult to distinguish the previous transfused product from the current product and 3) this approach cannot be usedwith autologous blood products since there is then no HLA mismatch. Therefore, we believe that despite higher platelet activation, biotinylated platelets should be the future gold standard in assessing platelet PTR. Future directives Our group is currently performing a trial in healthy volunteers (NTR 6493) to assess the safety and efficacy of biotinylated PLTs. Once proven safe and effective, biotinylated platelets will enable us to assess platelet clearance in numerous patient populations. Patient populations of special interest who often receive platelet transfusions are crit- ically ill patients, patients with a haematological malignancy and patients undergoing large surgeries. Correlations between patient related factors, such as fever and un- derlying disease with post transfusion recovery of platelets should be assessed. These findings can help design targeted therapy strategies. Furthermore, biotin labeling can be used to assess the quality of new platelet products. For instance, the use of new platelet additive solutions, the use of cryo-stored platelets or the effects of new patho- gen reduction therapies on PLT PTR. In our method we assessed the labelling of PLTs using a single concentration of biotin. Previously, it was shown in mice, that two different densities of biotin can be used to label PLTs making it possible to distinguish different PLT populations 26 . In the near future, we plan to explore the labelling of PLTs using different concentrations of biotin, enabling us to perform similar experiments as described in chapter 6, but now using platelets. This methods provides possibilities to use internal controls by transfusing two different platelet populations into one recipient. The use of internal controls will reduce the noise of inter-donor and/or inter-recipient variability. 9

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