(P-BC-38) In Vitro Quality of Red Cell Concentrates in PAGGSM Additive Solution Derived from a Whole Blood Collection Set Plasticized with Di (2-Ethylhexyl) Terephthalate

Di(2-ethylhexyl) phthalate (DEHP) has been the primary plasticizer in polyvinyl chloride (PVC) whole blood (WB) collection sets since the introduction of plastic blood storage systems. However, toxicity concerns have prompted upcoming regulatory changes that will effectively prohibit DEHP’s use in medical devices in Europe. Removal of DEHP is expected to particularly impact the in vitro quality of red blood cell (RBC) concentrates (RCC), as DEHP has long been known to leach from PVC, incorporate into RBC membranes, and favorably impact hemolysis and other aspects of the RBC storage lesion. Manufacturers are developing DEHP-free blood bag systems and assessing RBC additive solutions (AS) that may better preserve RBCs in the absence of DEHP. One potential PVC plasticizer/AS combination is di (2-ethylhexyl) terephthalate (DEHT)/phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM). This study compared the in vitro quality of RCC derived from WB collected in top/bottom collection sets made from PVC-DEHP with saline-adenine-glucose-mannitol (SAGM) or PVC-DEHT with PAGGSM.

Study

Design/Methods:

Approximately 480 mL WB was collected into CPD in either 500 mL DEHP/SAGM collection sets (Macopharma REF LQT710X) or prototype 475 mL DEHT/PAGGSM collection sets (Macopharma REF PRORQT4-B). Leukoreduced RCC were produced using a semi-automated top/bottom “warm” process. Briefly, WB was kept at room temperature overnight and separated on day D1. WB was centrifuged at 4898 x g for 10 min on a Roto Silenta (Hettich) centrifuge and extracted on a Macopress Smart Revo (Macopharma). RCC were stored refrigerated. Quality parameters, including hemolysis, supernatant potassium (K⁺) and RBC deformability using Lorrca (RR Mechatronics), were measured on D43 (1 day after expiry).  Non-parametric Mood’s Median tests were used to calculate statistical significance between RCC in DEHP/SAGM (n = 37) vs. DEHT/PAGGSM (n = 29).

Results/Findings:

D43 results are shown in Table 1. All units in the study had hemolysis < 0.8 % suggesting that RCCs in DEHT/PAGGSM produced using the “warm” production method would meet CAN/CSA-Z902:20 Blood and Blood Components hemolysis requirements for current RCC (≤ 0.8 % in at least 90% of units tested). Although hemolysis was slightly higher in DEHT/PAGGSM vs. DEHP/SAGM RCC, the difference was not statistically significant. Lorrca results suggest that RBCs in DEHT/PAGGSM are slightly less deformable (lower EI_MAX) and require larger amounts of force (K_EI) to physically deform.


Conclusions:

These data show acceptable hemolysis levels in RCCs in DEHT/PAGGSM, supporting a 42-day shelf-life for these components. However, results indicate removal of DEHP impacts RBC deformability.