The Usefulness of Improved, Newly Developed Polyolefin Container of Platelet, PO-100, with Higher Oxygen Permeability and Content

Abstract

The demand for platelet concentrate (PC) has been growing because of the increase of more intensive chemotherapy and hematopoietic stem cell transplantation, and highly invasive surgical operations of several specific areas (i.e. cardiovascular surgery, etc.), which has brought about considerable impact on its decent availability. Furthermore, the short storage period for room temperature stored PC, four days in Japan, five days in worldwide and seven days in the U.S. if they meet several requirements by FDA for the control of the risk of bacterial contamination, has put many PCs become outdated. In response to these requirements, measures have been taken to maximize platelet use, including development of polyolefin containers for platelets that elongate storage time and formulations of higher units. Here, we have developed a polyolefin container, PO-100, which has a 40%/m2 higher oxygen permeability than PO-80, a former, and standard platelet storage bags across the world. Furthermore, PO-100 has two types, one is PO-100/1000 with 1000mL capacity for 4-5 x 1011 platelets content and the other is PO-100/1500 with 1500mL capacity for over 6 x 1011 platelets content. In this study, we evaluated the influence of storage of higher content of platelet in PO-100 on the condition of platelet in the bag. The IRB of Nagasaki University approved this study. After informed consent was obtained from healthy volunteers, single-donor apheresis was performed. Then, platelets were pooled, separated equally into two types of bags, PO-100/1000 (n=6) or PO-100/1500 (n=6), and stored in plasma for up to day 7. We monitored various parameters, which related the quality of PC, in bags over the storage period. The result showed that the in vitro characteristics of platelets; platelet counts, mean platelet volume (MPV), and adenosine diphosphate (ADP)/collagen combined-induced platelet aggregation did not significantly change through 7 days storage period both in PO-100/1000 and PO-100/1500. Furthermore, MPV (fL) (8.63±0.35 vs 8.85±0.58, respectively, p=0.463) and platelet aggregation (%) (81.58±4.45 vs 84.67±1.21, respectively, p=0.118) were equivalent between these two conditions. Although pH gradually declined, it was maintained around 7.0 at day 7 without significant difference in both conditions (7.00±0.10 vs 6.92±0.08, respectively, p=0.063). On the other hand, lactate concentration elevated gradually, but there was no significant difference between two bags at day 7 (133.07±23.70 vs 104.52±15.56, respectively, p=0.097) and the pO2 declined by 30 to 40% from day 0 through day 1 in both conditions, suggesting aerobic metabolism was well maintained with efficient O2 consumption and less lactate accumulation in PO-110 bags regardless of its capacity. Intriguingly, our previous investigation demonstrated that pH and ADP-induced platelet aggregation in PO-80 bags decline steeply, notably after day 3, and values at day 7 were 6.67±0.24 and 56.67±11.34%, respectively, which suggested that higher oxygen permeability might contribute to keep platelets in better condition in PO-100 than PO-80. In conclusion, the present study demonstrated that PO-100 had significantly high utility as a noble container for PC. It was considered that better maintenance of the pH of the medium in PC within the appropriate range through improved higher oxygen permeability and efficient aerobic metabolism resulted in platelets in a better functional state even after 7 days storage. Furthermore, the results in this study might open the possibility of practical application of higher unit products, so that the supply chain of PCs could be conducted favorably. Disclosures Nagai: Kawasumi Laboratories Inc.: Research Funding; Kaneka Corporation: Research Funding; Ono Pharmaceutical Co.Ltd.: Consultancy. Yakushiji:Kawasumi Laboratories Inc.: Employment. Kino:Kawasumi Laboratories Inc.: Employment. Tokunaga:Kawasumi Laboratories Inc.: Employment. Yamaoka:Kawasumi Laboratories Inc.: Employment.