Combinations of Non-di(2-ethylhexyl) Phthalate Collection Sets, Storage Bags and Additive Solutions for Red Blood Cells

Abstract

For decades, di(2-ethylhexyl) phthalate (DEHP) has been the primary plasticizer used to make polyvinyl chloride (PVC) blood bags flexible. DEHP leaches into the blood product, stabilizing red blood cell (RBC) membranes and preventing excessive hemolysis. Despite being classified as a substance of very high concern due to its potential endocrine-disrupting and carcinogenic effects, DEHP has continued to be used in red cell concentrate (RCC) storage bags, as alternatives have often led to reduced RCC quality during storage. However, under the European Medical Device Regulation the use of DEHP in medical devices is restricted to below 0.1% by weight per July 2030. As a result, the effect of several alternative plasticizers on RCC quality, such as di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and N-butyryl-n-hexyl citrate (BTHC), have recently been investigated in combination with different storage solutions. Although previous studies using these new combinations showed variable results, these alternatives remain the most promising options, with current data demonstrating reduced leaching and lower toxicity compared to DEHP. This review highlights key publications on the transition from DEHP-PVC blood bag systems for RCC storage, demonstrating that several non-DEHP alternatives are viable replacement options, particularly when combined with next-generation storage solutions. Future studies are required to assess the frequency of adverse events, the occurrence of handling issues such as leakage, and to evaluate practical performance and clinical efficacy through post-transfusion recovery and increment studies.