Methodological strategies to study and elucidate RBC properties and their potential clinical impact on transfused patients

Transfusion is a life-saving practice that requires regular blood donation from healthy volunteers. Red blood cells (RBCs) are isolated from blood donation and stored as RBC concentrates (RCCs) at 4 °C for 42 to 49 days depending on storage solution. RBCs have been intensively studied in this context since World War II and a plethora of data has been obtained from identification and quantification of small molecules to cell function. It has become evident that the RBC properties can be affected by different parameters such as the manufacturing process and donor characteristics. These factors among others may exert a significant influence on transfusion efficacy and clinical outcomes. After a first part summarizing the impact of the transfusion chain on RBCs and the clinical outcomes (from donors to patients), this review will present different strategies from simple to complex models and from in vitro experiments to clinical trials to fully characterize the properties of RBCs. Furthermore, in silico modeling will be discussed. Beyond pre-analytical conditions, the experimental design might influence the findings. It is therefore essential to expose the RBCs to conditions adapted to the tested hypothesis to understand RBC behavior to optimize the transfusion outcome.