Rejuvenation solution as an adjunct cold storage solution maintains physiological haemoglobin oxygen affinity during early‐storage period of red blood cells

Abstract

Background Red blood cell (RBC) units accumulate morphologic and metabolic lesions during storage before transfusion. Pyruvate-inosine-phosphate-adenine (PIPA) solutions (Rejuvesol, Biomet, Warsaw, IN) can be incubated with RBC units to mitigate storage lesions. This study proposes a PIPA treatment process, termed cold 'rejuvenation', using Rejuvesol as an adjunct additive solution, to prevent biomechanical storage lesions while avoiding the 1 h PIPA incubation required with standard PIPA treatment. We compared the efficacy of cold to standard 'rejuvenation' in improving metabolic lesions that occur during cold storage of RBCs, without altering function.Methods Twelve leucoreduced, A-positive RBC units were obtained. Each unit was aliquoted into either control (standard storage), washed (W), standard rejuvenation (SR) or cold rejuvenation (CR) groups, the latter two requiring washing. A volume-adjusted dose of Rejuvesol was instilled into the CR group upon receipt (Day 3). After 15 days of storage, p50, RBC deformability, in-bag haemolysis and mechanical fragility were analysed. 'Any treatment' is defined as W, SR and CR, with comparisons in reference to control.Results Higher p50s were seen in rejuvenated groups (>30 mmHg vs. <19 mmHg; P < 0Á0001). Any treatment significantly increased elongation index (P = 0Á034) but did not significantly increase in-bag haemolysis (P = 0Á062). Mechanical fragility was not significantly different between groups (P = 0Á055) at baseline, but the control (CTL) group was more fragile after 2 h in a cardiac bypass simulation than any treatment (P < 0Á0001).Conclusions This study demonstrates that rejuvenation (standard or cold) prevents the leftward p50 shift of storage lesions without detrimental effect on RBC deformity, in-bag haemolysis or mechanical fragility.

Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport

“…This approach could improve post-storage RBC function not only via maintenance of the P 50 at near-normal values, but also via the increased erythrocytic ATP, which is necessary for enzymes functioning to defend RBC integrity and for blood flow-regulating vasoactivity that fine-tunes O 2 delivery. Indeed, cold “rejuvenation/PIPA treatment” attenuated storage-induced declines in deformability and the progressive increases in mechanical fragility and RBC lysis ( Evans et al, 2020 ). Among other potential downstream mechanisms of the benefits of preserving these critical organic phosphates, they may inhibit fatty acid desaturases, in turn limiting fatty acid accumulation ( Thomas et al, 2021 ).…”

Toward Translational Impact of Low-Glucose Strategies on Red Blood Cell Storage Optimization

“…These can include insufficient nitric oxide bioavailability, iron overload, reduced tissue perfusion, inflammation, immunomodulation, and many others . Due to this, attempts have been made to prevent or reduce the storage lesion including pH adjustments, modifications to additive solutions, , cryogenic preservation, , hypoxic storage, and the use of rejuvenating solutions to recover functional capabilities of RBCs. , To date, nearly all approaches to improve stored RBCs have not considered the significantly high level of glucose in whole blood collection and RBC storage solutions. Most anticoagulants and additive solutions contain glucose at concentrations at least 8 times greater than physiological levels and 5 times greater than levels often measured in the bloodstream of people with diabetes, a patient group whose RBCs often have many of the same properties as those of stored RBCs. , …”

Tools and metrics for the assessment of post‐storage performance of red blood cells: no one is left over

“…In this context, a valuable follow‐up to the Karafin study 1 would include measuring the baseline storage (and patient) RBC deformability. Despite discrepancies in the literature, 27 treatment of stored RBCs with rejuvenation solutions leads to no 28 or only partial 29 restoration of deformability and mechanical fragility of stored RBC. The mechanical stability of RBCs stored for either short or long periods does not improve or get worse, respectively, when reconstituted with plasma of healthy individuals at body temperature, representing a very early adverse response to the new conditions 30 .…”