The evaluation of cold-stored platelets

Platelets are an integral part of transfusion medicine. In Canada, over 80% of the platelet units for transfusion are produced via the buffy coat method from whole blood and stored in plasma. The storage condition is at 22°C under constant agitation for a maximum of 7 days. These are known as room temperature stored platelets (RPs). There are several disadvantages associated with RPs. First, RPs experience a significant decrease in platelet quality during storage known as the platelet storage lesion. Second, RPs have increased risks of microorganism growth. Last, RPs have a very limited shelf life which contributes to product wastage. Platelets stored at 4°C or cold-stored platelets (CPs) have been gaining renewed interest due to their potential of overcoming the disadvantages of RPs. Preliminary studies have shown that CPs have preserved mitochondrial functions, superior hemostatic functions and stable pH compared to RPs. Additionally, CPs have been hypothesized to be a superior product especially for bleeding patients. In this thesis, we compared the in vitro storage characteristics of CPs versus RPs over 14 days of storage. We showed that CPs have better aggregation response to physiological agonists and formed stronger clots compared to RPs. We also examined the underlying biological changes of CPs and RPs during storage by performing an untargeted metabolomic study. We showed that CPs exhibited significantly less metabolomic stress during storage compared to RPs as exemplified by the stable reduced glutathione pools in the CPs but not RPs. Additionally, we explored the potential benefits of CPs in bleeding scenarios by using an in vitro trauma transfusion model. From this experiment, we showed that donor whole blood mixed with CPs is more resistant to hyperfibrinolysis that is commonly observed in trauma. Finally, we explored the importance of oxidative stress in platelet storage by inhibiting the activity of the glucose 6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway. We found that RPs with G6PD inhibitors seem to have higher P-selectin expression and lower maximum clot firmness, indicating worse quality. These results indicate that CPs should be further considered as a transfusion product specifically for bleeding patients.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat