Cold stored platelets in the management of bleeding: is it about bioenergetics?

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

What is the context? To transition into an activated state, platelets require a highly efficient source of energy that is met through the production of ATP ­ this is referred to as "platelet bioenergetics"Platelets can be removed from healthy donors and used to make platelet concentrates for clinical usePlatelet concentrates are used clinically either therapeutically (to halt bleeding) or prophylactically (to prevent bleeding in patients with low platelet counts)They are stored at room temperature (20­24^oC) with constant gentle agitation, in packs that allow gas exchange and have a 7-day shelf life in some jurisdictionsStoring platelets in the cold (2­6^oC) has historically been shown to improve their ability to halt bleedingWhat is new? There is a renewed interest in cold stored platelets for use in actively bleeding patientsThere are benefits to cold-storing platelets over room temperature storageCold stored platelets are licensed in the US and Norway for certain indications for 14 daysWhat is next? Cold stored platelets have the potential to improve logistics of clinical supply of platelets, enable supply of platelet concentrates where access is currently limited, such as pre-hospital care and on the battlefield and provide improved hemostatic effects for bleeding patients.New research measuring the bioenergetic profiles of cold stored platelets could advance understanding of metabolism in cold stored platelets and support decisions on their re-introduction on a wider scale.

In vitro storage characteristics of neonatal platelet concentrates after addition of 20% PAS-E.

BACKGROUND AND OBJECTIVES: An observed decline in end-of-storage pH in plateletpheresis-derived platelet concentrates for neonatal use suspended in 100% autologous plasma was expected to be reversed by the addition of a platelet additive solution, (PAS)-E, increasing unit volume by approximately 20%. This study determined the impact on other in vitro storage parameters to ensure the expected increase in pH did not mask an adverse impact on component quality. STUDY DESIGN AND METHODS: For each replicate, one of a pair from a double adult dose plateletpheresis collection had approximately 50 ml of PAS-E added on Day 3 of storage. Its unmodified twin served as a control. Each adult dose was split into four neonatal storage packs and tested on Days 3, 6, 7 and 8. Three of 12 replicates were from donors with a history of low pH at end of storage and reflected the worst-case scenario for the new components. A further experiment evaluated whether any differences were simply due to the increased unit volume. RESULTS: In the nine randomly selected collections, pH on Day 8 was approximately 0.4 units higher in the test units. Platelet activation tended to be lower, with CD62P surface expression on Day 8 of 54.6 ± 9.9% compared to 65.8 ± 10.7% for controls (p < 0.001). Test units from donors with historically low pH retained pH22°C levels above 6.8 compared to controls (<6.4 on Day 8). CONCLUSION: The addition of 20% PAS-E by volume increased the buffering capacity of the units whilst maintaining other in vitro storage characteristics.