The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs

Abstract

Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.

A novel mouse model of red blood cell storage and posttransfusion in vivo survival

“…14 Moreover, the absence of plasticizer, present in human blood bags and reported to extend human RBC survival, may also be responsible. 15 It is important to note that the FDA requirement for 75% posttransfusion survival at 24 hours represents an average. Indeed, some units of RBCs stored under approved conditions for the appropriate length of time have substantially worse survival.…”

Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride

“…However, the use of PVC blood bags containing DEHP has been permitted in Japan without any regulation other than storage at low temperatures because DEHP has been found to be effective in preserving stored red blood cells (RBCs). 15 We recently developed a prototype of a novel and biologically safer blood container consisting of UV-irradiated PVC sheets 16 from which the elution of DEHP was almost suppressed. On evaluating the safety of the prototype, we found that the hemolytic ratio of the heparinized bovine blood stocked in the container was lower than that of the blood stored in normal PVC blood bags (data not shown).…”

In vitro evaluation of the quality of blood products collected and stored in systems completely free of di(2‐ethylhexyl)phthalate–plasticized materials

“…Despite research on alternative plasticizers including TOTM 14 or BTHC 15 or other polymers like polyolefines, 15,16 DEHP is still the plasticizer of choice for RBC storage containers because of the positive effect of DEHP on RBC stability. The presence of DEHP resulted in better retention of normal morphology, 17 enhanced osmotic stability, 18,19 decreased hemolysis, 18,20 and improved in vivo recoveries 24 hours after transfusion. 14,20 The plasticizer di(isononyl) cyclohexane-1,2dicarboxylate (DINCH), also known as Hexamoll DINCH (BASF SE, Ludwigshafen, Germany) is currently being discussed for its potential use in blood bags.…”