Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C–stored platelets

Abstract

BACKGROUND Cold (4°C)‐stored platelets are currently under investigation for transfusion in bleeding patients. It is currently unknown how long cold‐stored platelets can be stored for clinical applications. STUDY DESIGN AND METHODS Twenty three subjects were recruited. Twenty‐one subjects were available for in vivo assessment and received indium‐111 radiolabeled, cold‐stored platelets. We investigated 5‐ (n = 5), 10‐ (n = 6), 15‐ (n = 5), and 20‐day–stored (n = 5) platelets and obtained samples for in vitro testing at baseline and after the designated storage time. Twenty three units were available for in vitro testing. Five‐ and 7‐day (n = 5 each), room temperature (RT)‐stored platelets served as the current clinical standard control. RESULTS In vivo, we found a continuous decline in platelet recovery from 5 to 20 days. Platelet survival reached a low nadir after 10 days of storage. Ex vivo, we observed the maximum platelet αIIbβ3 integrin response to collagen at 5 days of cold storage, and we saw a continuous decline thereafter. However, platelet integrin activation and mitochondrial membrane integrity were better preserved after 20 days at 4°C, compared to 5 days at RT. Platelet metabolic parameters suggest comparable results between 20‐day cold‐stored platelets and 5‐ or 7‐day RT‐stored platelets. CONCLUSION In summary, we performed the first studies with extended, cold‐stored, apheresis platelets in plasma for up to 20 days with a fresh comparator. Storing cold‐stored platelets up to 20 days yields better results in vitro, but further studies in actively bleeding patients are needed to determine the best compromise between hemostatic efficacy and storage prolongation.

Refrigeration of apheresis platelets in platelet additive solution (PAS‐E) supports in vitro platelet quality to maximize the shelf‐life

“…In general, the observed changes to the platelet parameters were progressive in both RT and cold groups, but occurred at a slower rate in the cold-stored platelets. As previously shown, cold-stored platelets remained metabolically active throughout 21 days of storage, 5,15,[23][24][25] whereas glycolytic metabolism stalled in the RT-stored platelets in PAS by day 14. In contrast, residual glucose from 40% plasma was sufficient for 3 weeks when cold-stored, and PAS prevented acidification of the component.…”

“…However, it is prudent to keep in mind that the pH is only a surrogate marker of platelet quality, and it remains contentious as to whether it is predictive of clinical outcomes. 41,42 While it is well established that cold-storage is associated with reduced in vivo viability, 1,25,43 these indicators appear to be further affected by the composition of the storage solution. 11,12,25 Stolla et al, has recently demonstrated that in healthy human volunteers, in vivo platelet recovery was lower after storage for 10 days when platelets were supplemented with PAS (PAS-C and PAS-F), compared to platelets stored in plasma; however, the survival between the platelets in each group was similar.…”

“…41,42 While it is well established that cold-storage is associated with reduced in vivo viability, 1,25,43 these indicators appear to be further affected by the composition of the storage solution. 11,12,25 Stolla et al, has recently demonstrated that in healthy human volunteers, in vivo platelet recovery was lower after storage for 10 days when platelets were supplemented with PAS (PAS-C and PAS-F), compared to platelets stored in plasma; however, the survival between the platelets in each group was similar. 12 Importantly, the first contemporary clinical trial of coldstored platelets transfused units supplemented with PAS (PAS-C and PAS-E), and reported that they performed similarly to RT platelets for the treatment of bleeding in cardiac surgical patients.…”

Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage

“…Stolla et al 44 found that cold‐stored PLTs have a progressive decline in their survival upon autologous transfusion in humans within the first 10 days of storage with even further decline in the first 24‐hour recovery when they are cold stored for up to 20 days. Clustering of GPIbα on the PLT surface was noticed following refrigeration of PLTs 8 .…”

Platelet transfusion: The effects of a fluid warmer on platelet function

“…The current practice of storing PLTs at a room temperature of 22°C resulted from studies that demonstrated optimized circulating time and increase in PLT count in oncology patients but may not maximize or preserve PLT function 12 . Alternative methods to PLT and whole blood storage are being investigated and used—including cold storage (4°C) 13,14 …”