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Published on: June 2, 2023
Platelet Storage Quality, Plasticizer Migration, and Transfusion Exposure Risk in DEHP Versus Non-DEHP Blood Storage
Ludwig Rayner Frontier Ramos1, Wouter Van't Hof2, Quentin Brebant3
1Medical Affairs, Macopharma USA, 3075 Breckinridge Blvd, Suite 405, Duluth, GA 30096, USA.
The global transition away from di(2-ethylhexyl) phthalate (DEHP)-plasticized blood storage systems has raised important questions regarding platelet storage biology, transfusion performance, and recipient exposure to plasticizer-derived compounds. This systematic review evaluated platelet quality, plasticizer migration, and modeled transfusion exposure associated with DEHP-containing and DEHP-free platelet storage systems, including di(2-ethylhexyl) terephthalate (DEHT), diisononyl cyclohexane-1,2-dicarboxylate (DINCH), butyryl trihexyl citrate (BTHC), and tri(2-ethylhexyl) trimellitate (TOTM). English-language studies reporting quantitative platelet storage, migration, or exposure endpoints were identified through structured Google Scholar searches through 1 May 2025, supplemented by manual reference screening. Eligible studies were required to specify plasticizer composition and report quantitative biologic, migration, or exposure outcomes. Narrative reviews, opinion articles, and studies lacking extractable quantitative data were excluded. The risk of bias and the certainty of the evidence were assessed using adapted domain- and GRADE-based frameworks for mechanistic and preclinical studies. A random-effects meta-analysis was performed for day 7 platelet pH, while the remaining endpoints were synthesized descriptively. Thirty-three studies were included, comprising experimental platelet storage studies, biomaterial migration analyses, toxicologic investigations, and exposure-modeling studies. Platelet metabolic stability, including pH, glucose consumption, lactate accumulation, and mitochondrial membrane potential, was preserved across plasticizer systems. Meta-analysis demonstrated no significant difference in pooled day 7 platelet pH between DEHP and non-DEHP systems (mean difference +0.025; 95% confidence interval -0.081 to +0.131). Platelet aggregation and agonist-induced activation responses were maintained in DEHP-free systems. Selected activation and apoptotic markers, including CD62P expression and Annexin V binding, were reduced in fully DEHP-free systems, suggesting decreased storage-related membrane stress. Migration studies consistently demonstrated substantially greater DEHP leaching than DINCH and DEHT, resulting in higher modeled cumulative transfusion exposure, particularly among pediatric and neonatal recipients. Evidence further indicated that DEHP-containing whole-blood collection systems contribute to downstream contamination of platelet products with DEHP and mono(2-ethylhexyl) phthalate (MEHP). Interpretation is limited by heterogeneity in study design, storage platforms, assay methodologies, and the predominance of in vitro evidence. Overall, replacing DEHP with modern alternative plasticizers helps preserve transfusion-relevant platelet quality while potentially reducing plasticizer migration and modeled recipient exposure, thereby supporting the biologic and toxicologic rationale for transitioning to phthalate-free blood collection and storage systems.
The global transition away from di(2-ethylhexyl) phthalate (DEHP)-plasticized blood storage systems has raised important questions regarding platelet storage biology, transfusion performance, and recipient exposure to plasticizer-derived compounds. This systematic review evaluated platelet quality, plasticizer migration, and modeled transfusion exposure associated with DEHP-containing and DEHP-free platelet storage systems, including di(2-ethylhexyl) terephthalate (DEHT), diisononyl cyclohexane-1,2-dicarboxylate (DINCH), butyryl trihexyl citrate (BTHC), and tri(2-ethylhexyl) trimellitate (TOTM). English-language studies reporting quantitative platelet storage, migration, or exposure endpoints were identified through structured Google Scholar searches through 1 May 2025, supplemented by manual reference screening. Eligible studies were required to specify plasticizer composition and report quantitative biologic, migration, or exposure outcomes. Narrative reviews, opinion articles, and studies lacking extractable quantitative data were excluded. The risk of bias and the certainty of the evidence were assessed using adapted domain- and GRADE-based frameworks for mechanistic and preclinical studies. A random-effects meta-analysis was performed for day 7 platelet pH, while the remaining endpoints were synthesized descriptively. Thirty-three studies were included, comprising experimental platelet storage studies, biomaterial migration analyses, toxicologic investigations, and exposure-modeling studies. Platelet metabolic stability, including pH, glucose consumption, lactate accumulation, and mitochondrial membrane potential, was preserved across plasticizer systems. Meta-analysis demonstrated no significant difference in pooled day 7 platelet pH between DEHP and non-DEHP systems (mean difference +0.025; 95% confidence interval -0.081 to +0.131). Platelet aggregation and agonist-induced activation responses were maintained in DEHP-free systems. Selected activation and apoptotic markers, including CD62P expression and Annexin V binding, were reduced in fully DEHP-free systems, suggesting decreased storage-related membrane stress. Migration studies consistently demonstrated substantially greater DEHP leaching than DINCH and DEHT, resulting in higher modeled cumulative transfusion exposure, particularly among pediatric and neonatal recipients. Evidence further indicated that DEHP-containing whole-blood collection systems contribute to downstream contamination of platelet products with DEHP and mono(2-ethylhexyl) phthalate (MEHP). Interpretation is limited by heterogeneity in study design, storage platforms, assay methodologies, and the predominance of in vitro evidence. Overall, replacing DEHP with modern alternative plasticizers helps preserve transfusion-relevant platelet quality while potentially reducing plasticizer migration and modeled recipient exposure, thereby supporting the biologic and toxicologic rationale for transitioning to phthalate-free blood collection and storage systems.
