Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

Abstract

Background: The Mirasol® pathogen reduction technology (PRT) for platelet concentrates (PC) uses riboflavin and UV light (270–360 nm). We evaluated the impact of PRT on platelets in comparison to standard single-donor PC. Material and Methods: Platelets were resuspended in autologous plasma. After 2 h rest without agitation, PC were split into an untreated control unit (C-PC) and an immediately treated unit (T-PC) (series I). In series IV, split PC were stored under agitation over night before PRT was carried out. Platelet quality was assessed by pH, glucose consumption, lactate production rate, LDH, soluble sCD62p and CD62p expression with and without TRAP (thrombin receptor-activating peptide) over 7 days. Results: Series I: On day 5, pH values were lower for T-PC (6.8 ± 0.2 vs. 7.4 ± 0.1, C-PC), accompanied by a higher glucose consumption rate of 0.069 ± 0.016 vs. 0.035 ± 0.006 mmol/10¹² platelets/h and lactate production rate of 0.126 ± 0.031 vs. 0.063 ± 0.011 mmol/10¹² platelets/h. CD62p using TRAP was lower for T-PC (50 ± 11 vs. 62 ± 14%). Baseline activation was higher in T-PC (35 ± 12 vs. 28 ± 15%). Longer initial rest time had no impact on these results (series II/III/IV). Conclusion: PRT leads to an increase of platelet metabolism and activation independent of the length of the initial rest times. PC resuspended in autologous plasma should be stored at maximum up to day 5.

In vitro study of platelet function confirms the contribution of the ultraviolet B (UVB) radiation in the lesions observed in riboflavin/UVB‐treated platelet concentrates

“…A change of ATP consumption rate is another hypothesis for the increased glycolytic flux in riboflavin/UVB‐treated PLTs. Increased expression of P‐selectin and lower ATP content were reported in riboflavin/UVB‐treated PLTs . We also found an increased expression of CD62P, active GPIIbIIIa at the surface of the PLTs, and an increased adhesion to fibrinogen indicating that the riboflavin/UVB‐treated PLTs were somehow activated upon treatment.…”

“…The results from this study reveal that the riboflavin/UVB treatment significantly impacts the metabolism of PLTs as evidenced by higher glucose consumption and lactate production rates. This phenomenon has been observed by other groups in Mirasol‐treated PLTs . It has been hypothesized that the increased anaerobic glycolysis rate in riboflavin/UVB‐treated PLTs was either due 1) to an impaired mitochondrial functionality leading to a decrease of oxidative phosphorylation, 2) to an alteration of the PLT storage medium characteristics (pH, oxygen content, plasma protein content), or 3) to changes in ATP consumption rate …”

“…In vitro studies reported metabolic changes, impaired mitochondrial function, accelerated passive activation, and altered agonist‐induced PLT aggregation in INTERCEPT‐treated compared to untreated PLTs . Mirasol‐treated PLTs exhibit an increased expression of P‐selectin (CD62P), higher lactate production, and increased glucose and oxygen consumption, as well as lower ATP over storage time . The Mirasol PIT leads to hyperactive PLTs resulting in a reduced degranulation capacity upon acute stimulation …”

Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion

“…Importantly, treated PCs exhibit a higher platelet pre-activation level and are less reactive to stimuli, thus showing lower efficacy than untreated PCs [8,9,10]. In addition, a recent study reported that microparticulation was significantly increased in treated PCs as they approached their expiration date [11].…”

Effects of use of riboflavin and ultraviolet light for pathogen inactivation on quality of platelet concentrates

“…Dosadašnja ispitivanja pokazala su, takođe, da su bolesnici koji su primili transfuzije trombocita inaktivisanih primenom riboflavina i UV zračenja imali uporedive hemostatske i hematološke parametre nakon transfuzije trombocita sa bolesnicima koji su primili transfuzije netretiranih kontrolnih koncentrata trombocita 19,25,31 . Takođe, nisu zabeležene neželjene reakcije nakon transfuzije u ovoj grupi bolesnika.…”