Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use.

BACKGROUND: Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery. STUDY DESIGN AND METHODS: Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 ± 2°C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles. RESULTS: Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 µmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles. CONCLUSION: The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials.

Universal irradiation of platelets: Does irradiation affect the quality, effectiveness, and safety of platelets for transfusion?

We aimed to identify any detrimental effects on platelet quality and clinical effectiveness, of irradiated platelets compared to non-irradiated platelets for transfusion. The review was conducted in accordance with PRISMA guidelines. The protocol was prospectively registered on PROSPERO [CRD42023441930]. Our search identified 3002 references, of which we included 44 studies. Forty-one were in vitro only studies, two studies were in healthy volunteers, and one study reported clinical outcomes in thrombocytopenic patients. X-ray was used exclusively in three studies, and alongside gamma irradiation in one study. Two studies did not report the source of irradiation. The remaining 38 studies used gamma irradiation only. We assessed risk of bias (ROB) for studies reporting clinical and in vivo outcomes using ROB 2.0 (3 studies). We adapted a ROB tool designed for animal studies to assess ROB for the studies reporting in vitro outcomes (43 studies). We assessed the certainty of the evidence for the eight outcomes deemed most important to assess platelet quality and clinical effectiveness (where day 0 is the day of the blood draw). Overall, gamma irradiation has little to no effect on most markers of platelet quality and effectiveness. Where there is evidence of detriment from irradiation, differences are small in vitro, and are unlikely to affect clinical outcomes following transfusion. However, the evidence base is limited. Only half the studies could be included in any analysis. There is very limited evidence for x-ray as a source of irradiation and, given the potential benefits of using x-ray over gamma irradiation (ease of use and safety requirements), we would welcome further research comparing x-ray to gamma, and x-ray to a non-irradiated control.