Exploratory in vitro study of red blood cell storage containers formulated with an alternative plasticizer

Abstract

Background: The plasticizer di-2-ethylhexyl phthalate (DEHP) is a common component in medical plastics. There is motivation to replace this component; however, DEHP is necessary to prevent excessive hemolysis in stored red blood cells (RBCs). Our objective is to evaluate a candidate replacement plasticizer (Hexamoll, di-isononyl cyclohexane-1,2-dicarboxylic acid [DINCH], BASF Corp.) compared to DEHP in an in vitro feasibility study. We hypothesize that the candidate will provide at least equivalent protection against hemolysis for RBCs stored for 42 days and periodic mixing of RBCs will add additional protection against hemolysis.

Study design and methods: Whole blood was collected into citrate-phosphate-dextrose; combined into pools of 2 ABO identical whole blood units; and divided, leukoreduced, centrifuged, and separated into plasma and RBCs. Additive solution was added, and the RBCs were stored for 42 days at 1 to 6°C. In three parts of this study, split pools were paired as DINCH-polyvinyl chloride (PVC) with weekly mixing versus DINCH-PVC with no mixing, DINCH-PVC mixed versus DEHP-PVC no mix, and DINCH-PVC versus DEHP-PVC with neither mixed. A standard panel of in vitro RBC characteristics was determined on Days 0 and 42.

Results: Mixing DINCH-PVC weekly improved Day 42 hemolysis (0.36 ± 0.07% vs.0.56 ± 0.15%, p = 0.002), and mixed DINCH-PVC bags were noninferior to unmixed DEHP-PVC bags (p ≤ 0.05). DINCH-PVC bags stored without weekly mixing were inferior to unmixed DEHP-PVC bags for hemolysis on Day 42, although no individual bag exceeded 0.8% hemolysis.

Conclusion: Periodic mixing of RBCs stored in DINCH-PVC provides additional protection against hemolysis. Unmixed DINCH-PVC bags were inferior to DEHP-PVC bags for prevention of hemolysis, but remain a candidate for replacement DEHP in RBC storage bags.