Increased blood ammonium concentrations cause neurological complications. Existing drugs are not always sufficiently effective. Alternatively, erythrocytes-bioreactors (EBRs) loaded with enzymes utilizing ammonium, were suggested for ammonium removal from blood. However all they worked only for a short period of time. The reasons for this were not investigated. In this study, EBR mathematical models were developed and analysed based on the reactions of glycolysis and different enzymes utilizing ammonium, which showed that the efficiency and duration of EBRs’ functioning could be limited due to low permeability of the cell membrane for some key substrates and products. A new enzyme system including glutamate dehydrogenase and alanine aminotransferase was proposed and realised experimentally, which was not limited by cell membrane permeability for glutamate and α-ketoglutarate due to creating metabolic pathway where these metabolites were produced and consumed cyclically. New bioreactors removed ammonium in vitro at the rate of 1.5 mmol/h × lRBCs (for human bioreactors) and in vivo in a model of hyperammoniemia in mice at the rate of 2.0 mmol/h × lRBCs (for mouse bioreactors), which correlated with model calculations. Experimental studies proved the proposed mathematical models are correct. Mathematical simulation of erythrocyte-bioreactors opens new opportunities for analysing the efficiency of any enzyme included in erythrocytes.

Background Transmission of pathogens through blood transfusion is still of great concern to clinicians, patients and blood providers. Pathogen reduction technologies (PRT) have been successfully applied for the treatment of labile blood components, such as plasma, platelets and whole blood (WB), which are now used in routine in many countries. We report the clinical evaluation of suspension of red blood cells (RBC‐S) derived from the WB treated with riboflavin and UV light (RF+UV). Study Design and Methods Seventy paediatric patients (0·3–17·1 years old) suffering from different malignant disorders were recruited and assigned to two groups: the control group (C) received transfusions of γ‐irradiated RBC‐S. The experimental group (T) received RBC‐S derived from WB, treated with RF+UV. Clinical efficacy was evaluated during follow‐up periods by Hb and Ht increments, and needs for transfusion support. Safety was assessed through active surveillance, recording post‐transfusion reactions, anti‐erythrocyte's antibody formation, haptoglobin and serum potassium levels. Results The clinical efficacy of RBC‐S in both groups was similar: mean post‐transfusion Hb concentration (101·6 ± 7·57 g/l vs. 100 ± 8·3 g/l; P = 0·43), and Ht level (28·5 ± 2·42% vs. 28·2 ± 2·7%; P = 0·66). Transfusion of pathogen‐reduced RBC‐S did not increase the frequency of transfusion reactions and did not induce an excessive immune response in the follow‐up period. Conclusion Transfusion of RBC‐S, obtained from pathogen‐reduced WB, is a promising method to increase the safety of blood component therapy for paediatric patients with malignant disorders without affecting clinical efficacy. A randomized clinical trial including more patients should follow this pilot study to confirm its results.