Pilot study on novel blood containers with alternative plasticizers for red cell concentrate storage

Abstract

Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl chloride (PVC) blood containers, is eluted from the blood containers and exerts protective effects on red blood cells. However, a concern for detrimental effects of DEHP on human health has led to the development of potential DEHP substitutes. Here, we compared the red blood cell preservation ability of two types of non-DEHP blood containers with safe alternative plasticizers to that of DEHP blood containers. Red cell concentrates in mannitol-adenine-phosphate solution (MAP/RCC) were stored for 6 weeks in PVC blood bags containing DEHP, di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH) and di (2-ethylhexyl) 4-cyclohexene-1,2-dicarboxylate (DOTH), or 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH) and DOTH. There was no significant difference in the total amount of plasticizer eluted into MAP/RCC (till 3 weeks from the beginning of the experiment), hemolysis of MAP/RCC, and osmotic fragility of MAP/RCC between the non-DEHP blood containers and DEHP blood containers. Hematological and blood chemical indices of MAP/RCC in all containers were nearly the same. Thus, DOTH/DINCH and DOTH/DL9TH blood containers demonstrate the same quality of MAP/RCC storing as the DEHP blood containers. Since DOTH, DINCH, and DL9TH were reported to be safe, DOTH/DINCH and DOTH/DL9TH blood containers are promising candidate substitutes for DEHP blood containers.

Migration of di(2‐ethylhexyl) phthalate, diisononylcyclohexane‐1,2‐dicarboxylate and di(2‐ethylhexyl) terephthalate from transfusion medical devices in labile blood products: A comparative study

“…Lagerberg et al showed an increasing plasticizer concentration along the storage of RBC (from D1 to D42) ranging from 4.1 ± 0.9 to 33.0 ± 11.0 μg/mL for DEHP and from 0.2 ± 0.1 to 4.5 ± 0.9 μg/mL for DINCH [4]. The same observation was noted by Morishita et al during the storage of RBC in PVC‐DEHP bags with DEHP concentrations from 2.60 ± 0.72 μg/mL to 22.0 ± 4.4 μg/mL at D1 and D42, respectively [31]. Our study highlights the same phenomenon for DEHT in RBC, namely, a concentration increases from 0.50 ± 0.46 to 7.12 ± 0.74 μg/mL, along the storage period.…”

“…Number of replicates for each condition: n = 3. *Statistically different ; **non-statistically different.± 4.4 μg/mL at D1 and D42, respectively[31]. Our study highlights the same phenomenon for DEHT in RBC, namely, a concentration increases from 0.50 ± 0.46 to 7.12 ± 0.74 μg/mL, along the storage period.…”

“…blood products has already been demonstrated in several studies for DEHP and DINCH[4,5,7,31].Lagerberg et al showed an increasing plasticizer concentration along the storage of RBC (from D1 to D42) ranging from 4.1 ± 0.9 to 33.0 ± 11.0 μg/mL for DEHP and from 0.2 ± 0.1 to 4.5 ± 0.9 μg/mL for DINCH[4]. The same observation was noted by Morishita et al during the storage of RBC in PVC-DEHP bags with DEHP concentrations from 2.60 ± 0.72 μg/mL to 22.0 F I G U R E 3 Evolution of the concentration of (a) plasticizer (di(2-ethylhexyl) phthalate [DEHP], diisononylcyclohexane-1,2-dicarboxylate [DINCH] and di(2-ethylhexyl) terephthalate), (b) plasticizer breakdown product (mono(2-ethylhexyl) phthalate [MEHP], monoisononylcyclohexane-1,2-dicarboxylate [MINCH] and mono(2-ethylhexyl) terephthalate [MEHT]) and (c) equivalent plasticizer (plasticizer + plasticizer breakdown product), during the 30 days of plasma storage.…”

Recommendations for in vitro evaluation of blood components collected, prepared and stored in non‐DEHP medical devices

“…This study also reported a higher rate of osmotic fragility, as well as decreased deformability when storing in BTHC and DINCH. Yet another study [7], also using SAGM, found no differences when comparing haemolysis between DEHP and a di (2‐ethylhexyl) 4‐cyclohexene‐1,2‐dicarboxylate (DOTH)/DINCH combination. In this study, baseline haemolysis rate (t = 0) was, however, already substantial (0.4%), while some units were close to exceeding 0.8% haemolysis in the third week of storage, which is the maximum amount of haemolysis that European countries adhere to in their guidelines when storing up to 6 weeks (Guide to the preparation, use and quality assurance of blood components, EDQM, 2020).…”

Impact of the pathogen inactivation process on the migration of di(2‐ethylhexyl) phthalate from plasma bags

“…The release of plasticizers from a medical device depends on the type of LBP and the storage conditions (temperature and duration) [3][4][5][6][7][8][9]; the higher the temperature and the longer the storage period, the greater the release of DEHP [5,[8][9][10]. The quantity of DEHP released by the medical device also depends on the nature of the LBP [1,4,5,7,9,11].…”