Non‐phthalate plasticizer DEHT preserves adequate blood component quality during storage in PVC blood bags

Abstract

Background and objectives Commercial blood bags are predominantly made of polyvinyl chloride (PVC) plasticized with di(2‐ethylhexyl) phthalate (DEHP). DEHP is favourable for storage of red blood cells (RBC). Historically, removal of DEHP from blood bags has been linked to unacceptable haemolysis levels. Oncoming regulatory restrictions for DEHP due to toxicity concerns increase the urgency to replace DEHP without compromising RBC quality. Di(2‐ethylhexyl) terephthalate (DEHT) is one suggested substitute. The aim of this study was to compare PVC‐DEHT to PVC‐DEHP blood bags using additive solutions saline–adenine–glucose–mannitol (SAGM) and phosphate–adenine–glucose–guanosine–saline–mannitol (PAGGSM), to determine whether DEHT can maintain acceptable component quality. Materials and methods RBC concentrates (N = 64), platelet concentrates (N = 16) and fresh frozen plasma (N = 32) were produced from whole blood collected into either DEHT or DEHP plasticized systems. Using a pool‐and‐split study design, pairs of identical RBC content were created within each plasticizer arm and assigned either SAGM or PAGGSM. Storage effects were assessed weekly for 49 days (RBC), 7 days (platelets) and before/after freezing (plasma). Results Though haemolysis was slightly higher in DEHT, all study arms remained below half of the European limit 0·8%. K+ was lower in DEHT than in DEHP independent of additive solution. The metabolic parameters were not influenced by choice of plasticizer. Platelet activation/metabolism and plasma content were similarly preserved. Conclusion Our study demonstrates that the plasticizer DEHT provides adequate blood component quality. We propose DEHT as a strong future candidate for replacement of DEHP in blood bags.

DEHT is a suitable plasticizer option for phthalate‐free storage of irradiated red blood cells

“…RMVs are shed from the RBC membrane as part of the storage lesion process, as ROS increases and antioxidants and ATP are depleted [2]. In this study, the generation of RMVs had similar but earlier onset than in non‐irradiated units [23]. This is likely attributed to increased ROS generation caused by irradiation, both directly and through the positive feedback loop provided by the haemolysis‐induced increase of free haemoglobin [11, 12].…”

“…Membrane proteins of ATPase character control the asymmetry between the inner and outer leaflet, and when ATP levels decrease, there is a progressive translocation of phosphatidylserine to the outer leaflet [27], where it plays a signalling role for phagocytosis [28]. The literature is ambiguous as to whether the percentage of phosphatidylserine positive RMVs from non‐irradiated RBCs increases during storage or not; several studies, our own previous study included, seem to suggest that it does not [23, 29, 30]. However, as irradiation induces increased oxidizing damage to membrane‐bound proteins [11, 12], it may be hypothesized that the observed increase in the frequency of RMVs exposing phosphatidylserine may be a consequence of irradiation damage.…”

Survey of blood centre readiness regarding removal of DEHP from blood bag sets: The BEST Collaborative Study

“…for DEHT blood bags with PAGGS-M storage solution; however, these values were still higher compared to the values for DEHP blood bags with SAGM storage solution throughout the 49-day RBC storage period [10]. Similarly, Graminske et al reported higher haemolysis levels for DEHT with PAGGS-M compared to DEHP with AS-1 at the end of the 42-day storage period [11].…”

“…Conversely, shelf-life can be shortened to provide RBC products with lower haemolysis. Current non-DEHP alternatives result in increased haemolysis during blood storage, requiring reconsideration of the RBC shelf-life [9][10][11][12]. In order to mitigate this impact, research is moving towards 'alternative combinations' of new plasticizers with new RBC storage solutions [12,13].…”

“…Respondents were not clear on the best non-DEHP vinyl material and RBC storage solution. Responses may have been influenced by studies showing that haemolysis levels with DEHT or DINCH in combination with PAGGS-M were similar to those with DEHP[10][11][12].Larsson et al …”