Platelet Quality and Function Variability across Collection Platforms and during Storage: Findings from the Ongoing Chilled Platelet Study in Vitro (CHIPSiv)

Introduction

Platelet concentrates (PLT) are primarily collected by apheresis on three machines in the United States and are stored in either plasma or platelet additive solution (PAS). The short shelf-life of PLT contributes to frequent shortages. Storage of PLT at 4°C has been investigated as a method to extend their shelf-life, but the effects of collection methods on these cold-stored platelets (CS-PLT) remain uncertain. The ongoing Chilled Platelet Study (CHIPS) trial (NCT04834414) includes an extensive in vitro arm (CHIPSiv) to investigate PLT quality metrics of differentially manufactured PLT. Here we present an interim analysis comparing the effect of different manufacturing methods on end-storage function in both room temperature and cold-stored units.

Materials and Methods

Apheresis PLT (n=124) were manufactured at two sites across four platforms, these collections comprising 62 paired donations from unique single donors with one unit stored at room temperature (RT; 22°C, agitated) and the other stored in the cold (4°C, not agitated consistent with current blood banking practice): Trima in plasma (TP, n=14), Trima in PAS: Isoplate (TI, n=18), Amicus in plasma (AP, n=14), and Amicus in PAS: Intersol (AI, n=15). Initial target yield was 4.5 for all collections. Hemostatic function was assayed on days 0 and 7 for room temperature-stored PLT, and on days 0, 7, 14, and 21 for cold-stored PLT. Complete blood counts, biochemistry, and hemostatic function were analyzed. Data are reported as median (interquartile range).Collection characteristics were compared using 1-way ANOVA. A 2-way ANOVA (Tukey’s test) was performed for quality and functional metrics;if significant, within-platform comparison was performed on day 7 of room temperature storage (RT-D7) and day 21 of cold storage (CS-D21).

Results

Interestingly, Amicus collections took longer compared to Trima groups [TP vs. AP (p<0.001), TP vs. AI (p<0.0001), and TI vs. AP (p<0.01), TI vs. AI (p<0.0005)]. Additionally, the unit volume was highest in TI, showing a statistical difference with TP (p<0.0001) and AP (p<0.0001), but not with AI. Platelet count varied across platforms in CS (p<0.001) but not during RT storage (p=0.7). On CS-D21, the platelet count was highest in AI (1027 x 10³/uL) compared to TP (854.1 x 10³/uL), TI (842.3 x 10³/uL), and AP (583.7 x 10³/uL). However, no such difference was observed on RT-D7. On CS-D21, lactate levels were 10.94 mmol/L in AI [TP vs. TI (p<0.0001), TI vs. AP (p<0.001), TI vs. AI (p<0.001)] and 12.90 mmol/L on RT-D7 [TP vs. TI (p<0.01), TI vs. AP (p<0.01), TI vs. AP (p<0.01)]. On the other hand, glucose levels on CS-D21 and RT-D7 were 22.50 mg/dL and 29 mg/dL, respectively, in AI, showing statistically significant differences with other groups (p<0.0001). Platelet aggregation by light transmission aggregometry (LTA) with dual agonist (ADP+Collagen) showed no difference on CS-D21 across platforms, but on RT-D7, the Trima groups showed higher aggregation than the Amicus groups [TP vs. AP (p<0.001), TI vs. AP (p<0.001), TI vs. AI (p<0.01)]. Thrombin generation capacity measured via calibrated automated thrombogram (CAT) was the same across platforms on CS-D21 but not for RT-D7 [TP vs. TI (p<0.01), TI vs. AP (p<0.01)]. Maximum clot firmness (MCF) from rotational viscoelastometry (ROTEM) appeared to be different across platforms for both CS-D21 [TP vs. TI (p<0.0001), TP vs. AI (p<0.0001), TI vs. AP (p<0.01), AP vs. AI (p<0.0001)] and RT-D7 [TP vs. TI (p<0.01), TP vs. AP (p<0.01), TP vs. AP (p<0.0001), AP vs. AI (p<0.0001)].

Conclusions

Variability in PLT quality and function was evident across collection platforms at baseline and throughout storage. AI consistently underperformed compared to other platforms despite retaining the high count throughout storage, suggesting that storage solution and collection device may mediate this difference, and furthermore, that platelet count alone is an insufficient metric for PLT quality. Continued research is needed into the effects of PLT platform on hemostatic function.