Background/Case Studies: Polyvinyl chloride (PVC) blood bags plasticized with di(2-ethylhexyl)phthalate (DEHP) have long been the standard for red blood cell (RBC) storage due to DEHP’s ability to stabilize cell membranes during refrigerated storage. However, DEHP is associated with potential toxicological concerns, including endocrine disruption and carcinogenicity, prompting regulatory agencies and manufacturers to seek safer alternatives. One such candidate is di(2-ethylhexyl)terephthalate (DEHT), a non-phthalate plasticizer with a similar stabilizing effect but without the known toxic effects of DEHP. While DEHT has been evaluated under normoxic storage conditions, its compatibility with hypoxic RBC storage, a method shown to enhance RBC preservation, remains underexplored.
Study
Design/Methods: Sixteen units of 1-day-old leukocyte-reduced RBCs in AS-3 were obtained from an AABB/FDA-licensed blood bank. For each replicate, four ABO-matched units (300–340 mL) were pooled and divided equally into four storage conditions: (1) PVC-DEHP, (2) PVC-DEHT, (3) DEHT-hypoxic, and (4) DEHP-hypoxic. Hypoxic units were processed using a CE-marked O₂/CO₂ reduction system on a linear shaker at 72 CPM for 3 hours at room temperature, then transferred into DEHT or DEHP hypoxic storage bags. All units were stored at 1–6°C for 42 days. RBC quality (ATP, 2,3-DPG, hemolysis) was assessed pre- and post-treatment and weekly. Data were analyzed by repeated-measures ANOVA with Newman Keuls post hoc test.
Results/Findings: The results are summarized in Table 1 as means ± standard deviations from four independent pools of LR-RBCs (N=4). The percent oxygen saturation of hemoglobin (%sO₂) and partial pressure of carbon dioxide (pCO₂) were significantly lower in hypoxic/hypocapnic RBCs (Groups C and D) compared to conventional storage (Groups A and B), confirming effective O2/CO2 reduction. ATP, 2,3-DPG, and lactate levels were higher in hypoxic RBCs on Days 21 and 42, indicating better preservation of metabolic function. Hemolysis levels on Day 42 remained below regulatory thresholds (FDA 1.0% and EU 0.8%) in all groups: A (0.29%), B (0.48%), C (0.52%), D (0.43%). Conclusions: Hypoxic RBC storage in DEHT plasticized bags preserves cell quality, including ATP, 2,3-DPG, and hemolysis, comparable to DEHP. Our findings support DEHT as a viable replacement for DEHP in hypoxic storage systems, facilitating the transition toward phthalate-free blood products without compromising RBC integrity.
