Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Abstract

Background: In vitro function of stored platelet (PLT) con-centrates was analyzed after applying two different techniques of pathogen reduction technology (PRT) treatment, which could increase cellular injury during processing and storage. Methods: Nine triple-dose PLT apheresis donations were split into 27 single units designated to riboflavin-UVB (M) or psoralen-UVA (I) treatment or remained untreated (C). Throughout 8 days of storage, samples were analyzed for annexin V release, the mitochondrial transmembrane potential (ΔΨ) and some classical markers of PLT quality (pH, LDH release, hypotonic shock response (HSR)). Results: PLT count and LDH release of all units maintained initial ranges. All units exhibited a decrease in pH and HSR and an increase in annexin V release and ΔΨ disruption. Notably, throughout the entire storage period, annexin V release re-mained lowest in M units. Throughout 7 days of storage, M units remained comparable to C units (p > 0.05), whereas inferior values were observed with I units. Here, differences to C units reached significance by day 1 (pH: p < 0.0001), day 5 (annexin V release: p < 0.014), and day 7 (HSR, ΔΨ: p ≤ 0.003). After PRT treatment, annexin V release and ΔΨ disruption were significantly (p < 0.001) correlated with pH and HSR. Conclusion: During storage, all units showed a de-crease in HSR and an increase in acidity, annexin V release and ΔΨ disruption. While M units remained comparable to C units, I units demonstrated significantly inferior values dur-ing terminal storage. This could have resulted from differences in PRT treatment or simply be due to differences in storage media and should be analyzed for clinical relevance in future investigations.

In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma‐irradiated platelets

“…A decrease in HSR to a varying degree has been reported for INTERCEPT and MIRASOL as well . The reason for the discrepancies seen in our study compared to other studies on UVC‐treated PLTs, and between studies of PLTs treated with INTERCEPT or MIRASOL, is not clear.…”

In vitro assessment of buffy‐coat derived platelet components suspended in SSP+ treated with the INTERCEPT Blood system

“…Overall, INTERCEPT treatment and subsequent storage increased glycolytic metabolism and activation compared to control units, as evidenced by a reduction in pH, an increase in glucose consumption, lactate production, exhaustion of ATP, CD62P expression and release and compromised collagen‐induced aggregation. Despite the observed differences, the impact on the in vitro quality of INTERCEPT platelets did not appear to be as marked as changes reported previously (Picker et al ., , ). However, the changes were particularly evident from day 5 of storage and therefore extension of the shelf‐life of treated platelets should be carefully considered.…”

“…Damage to platelet mitochondria can also lead to impaired oxidative phosphorylation. Previous studies examining apheresis platelets have demonstrated that INTERCEPT leads to a significant increase in mitochondrial membrane depolarisation during storage (Picker et al ., 2009a, 2009b, 2010). However, the effect of INTERCEPT on the mitochondrial membrane potential has not been previously examined in whole blood‐derived PCs stored in PAS.…”

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on in vitro platelet quality parameters

“…However, the combination of UVC‐treatment and cold‐storage also induced mitochondrial damage. The disruption to mitochondrial integrity may also contribute to membrane instability and cell swelling .…”