DEHP Alternative Blood Bag Quality Explored

A paper published in Vox Sanguinis examined, “the in vitro quality of red blood cell concentrates (RCCs) produced from whole blood (WB) collected in di(2-ethylhexyl) terephthalate (DEHT)/phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) bag sets” as an alternative to di(2-ethylhexyl) phthalate (DEHP)/saline-adenine-glucose-mannitol (SAGM) sets. The DEHP alternative blood bag quality study included, “500-mL DEHP/SAGM (n = 37) and prototype 475-mL DEHT/PAGGSM (n = 29) blood bag sets [compared] in independent study arms.” The authors explained that, [a]lthough the current DEHP/SAGM bags used at Canadian Blood Services have a 500-mL volume, the prototype DEHT/PAGGSM bags had a 475-mL volume, chosen to better align with our 480-mL nominal WB collection volume. In vitro quality of leu[k]oreduced RCCs (LR-RCCs) post-expiry was the main outcome assessed.”

The DEHP alternative blood bag quality study found that, “[a]t expiry, there was no statistically significant difference in supernatant K⁺ levels between DEHP/SAGM and DEHT/PAGGSM RCCs (47.8 ± 4.7 mmol/L and 48.8 ± 3.7 mmol/L, respectively; p = 0.346). DEHT/PAGGSM RCCs had slightly higher mean h[e]molysis levels at expiry; however, this difference was not statistically significant (0.29 percent ± 0.10 percent in DEHP/SAGM vs. 0.33 percent ± 0.12 percent in DEHT/PAGGSM; p = 0.083). There was statistically significantly higher free Fe²⁺ in DEHT/PAGGSM units at Day 43 (5.7 ± 1.1 μmol/L in DEHP/SAGM and 8.4 ± 1.9 in DEHT/PAGGSM; p < 0.001). Overall, the expected metabolic changes with RBC storage lesion were observed in both arms; however, there were some differences between arms. Adenosine triphosphate (ATP) was statistically significantly higher at Day 43 in DEHT/PAGGSM RCCs compared to DEHP/SAGM RCCs (3.23 ± 0.58 μmol/gHb and 2.83 ± 0.5 μmol/gHb, respectively; p = 0.004;). Supernatant glucose levels were statistically significantly lower in DEHT/PAGGSM versus DEHP/SAGM RCCs at expiry (15.4 ± 1.7 mmol/L and 18.1 ± 2.3 mmol/L, respectively; p < 0.001), despite PAGGSM having a higher level of starting glucose. [Additionally, the DEHP alternative blood bag quality found that there] was no difference in supernatant lactate levels between DEHT/PAGGSM and DEHP/SAGM RCCs at expiry (23.6 ± 2.4 mmol/L and 23.5 ± 2.8 mmol/L, respectively; p = 0.976;). Lorrca analysis indicated that DEHT/PAGGSM RBCs are less deformable than DEHP/SAGM RBCs (maximum elongation index [EI_MAX]; 0.581 ± 0.015 and 0.611 ± 0.010, respectively; p < 0.001) and require larger amounts of force (K_EI) to physically deform (2.300 ± 0.288 and 1.834 ± 0.177, respectively; p < 0.001). Osmoscan analysis revealed osmotic fragility differences between DEHP/SAGM and DEHT/PAGGSM RBCs. O_min, O_hyper, O_max and ΔO are all lower in DEHT/PAGGSM, suggesting an overall shift in the osmolality curve to the left (all p < 0.001).”

The researchers of the DEHP alternative blood bag quality study concluded that, “our study findings reiterate the need to focus research on DEHP alternatives on impacts to the red blood cell (RBC) membrane, with interrogation of h[e]molysis, microvesicle release, membrane composition, morphology, deformability and osmotic fragility likely to shed the most light on how RBC products will look in a DEHP-free future.” Limitations of the study included, “it was not a pool and split study design and did not address changes in the additive solution and plasticizer separately; [t]here was a higher proportion of male donors in the study, not reflective of Canadian Blood Services usually balanced male/female donor ratio; while the study was conducted using nominal processing conditions, such as temperatures and processing times, the approach taken was to conduct the study closer to the ‘worst case for quality’ of these nominal conditions (e.g., processing closer to the end of the allowable time ranges, if feasible). Therefore, the results of this DEHP alternative blood bag quality study may skew towards a worst-case scenario for product quality, something that may be viewed as a study limitation, but also a potential strength.”

Citation: Stephenson, T., Howell, A., Olafson, C. et al. “In vitro quality of whole blood-derived red cell concentrates collected, processed and stored in a blood bag set plasticized with di (2-ethylhexyl) terephthalate.” Vox Sanguinis. 2025.