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

Yuki Morishita,Ken-Ichi Miyazaki,Hitoshi Okazaki,Ken-Ichi Inamura,Tomokazu Mukai,Hisatoki Yamaoka,Toshiyasu Yuba,Yusuke Nomura,Tsuyoshi Kawakami,Yuji Haishima,Chie Fukui,Toshiyuki Ikeda,Hiroyoshi Ariga

doi:10.1371/journal.pone.0185737

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.

Highlights

Polyvinylchloride (PVC) has been widely used for the construction of medical devices, including blood containers, due to its durability and chemical inertness [1]
We recently reported that the concurrent use of DOTH and DINCH enabled the production of a safe polyvinyl chloride (PVC) sheet with protective effects on red blood cells, which was comparable to that of Di (2-ethylhexyl) phthalate (DEHP) [18]
One-way analysis of variance (ANOVA) analysis followed by post hoc TukeyKramer test for values obtained each week demonstrated that the total amount of plasticizer eluted from the DOTH/DL9TH blood container was not significantly different compared with that eluted from the DEHP blood container, but the levels determined in the DOTH/DINCH group were significantly higher than those of the DEHP group at 4–6 weeks

Summary

Introduction

Polyvinylchloride (PVC) has been widely used for the construction of medical devices, including blood containers, due to its durability and chemical inertness [1] As it is inflexible, to produce medical devices, the use of plasticizers is required. For the use in blood bags, alternative plasticizers should be safer, and have protective effects on red blood cells comparable to those of DEHP. We recently reported that the concurrent use of DOTH and DINCH enabled the production of a safe PVC sheet with protective effects on red blood cells, which was comparable to that of DEHP [18]. Using a novel plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH), we developed a PVC sheet for blood containers with comparable protective effects on red blood cells and improved cold resistance, compared to the characteristics of DEHP-PVC sheet [19]. We compared the potential for red blood cell preservation in the DOTH/DINCH- and DOTH/DL9TH-PVC blood containers, and that in the DEHP blood containers

Materials and methods

Results

Discussion