Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis‐mediated pathways

Abstract

Background Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold‐stored platelets (CSPs) and RTPs after 5‐day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days. Study Design and Methods This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial‐associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics. Results CSP preserved mitochondria‐associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro‐apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs. Conclusion Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well‐documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.

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

“…Until recently cold-stored platelets were only approved for use with a 3 day shelf-life; 21 although this can now be extended to 14 days if certain criteria are met. 14,22 While the shelf-life should be dictated by balancing the logistic benefits of a longer shelf-life with both product safety and in vivo hemostatic efficacy; these parameters may be impacted by the storage temperature and solution.…”

“…While it is feasible that the shelf‐life of cold‐stored platelets will exceed that of RT platelets, there is not yet a consensus on what the optimal shelf‐life of this product should be. Until recently cold‐stored platelets were only approved for use with a 3 day shelf‐life; 21 although this can now be extended to 14 days if certain criteria are met 14,22 . While the shelf‐life should be dictated by balancing the logistic benefits of a longer shelf‐life with both product safety and in vivo hemostatic efficacy; these parameters may be impacted by the storage temperature and solution.…”

“…Many studies have assessed the impact of cold‐storage on platelet quality when stored in either plasma or a combination of plasma and various platelet additive solutions (PASs) 4‐10 . Further, more recently, comparisons between cold‐stored platelets in plasma and PAS have been performed 11‐15 . However, variability in the study design, additive solution used, and manufacturing practices makes the transferability of data between blood collection centers with differing processes challenging.…”

“…[4][5][6][7][8][9][10] Further, more recently, comparisons between cold-stored platelets in plasma and PAS have been performed. [11][12][13][14][15] However, variability in the study design, additive solution used, and manufacturing practices makes the transferability of data between blood collection centers with differing processes challenging.…”

Cold‐stored platelets have better preserved contractile function in comparison with room temperature‐stored platelets over 21 days

“…Although using smaller bags instead of full-size platelet units is a limitation of this study, previous studies have demonstrated the usefulness of these bags in platelet storage for reducing introduction of donor-related variability into the outcomes. 19,23,24 Concentrations were adjusted to 300,000 platelets/μl using thawed fresh frozen plasma (FFP) collected and frozen after PRP separation from whole blood for all experiments in order to account for the effects of plasma degradation over time. 15 Detailed methods are described in the supplemental materials.…”