title: The purified vepoloxamer prevents haemolysis in 42-day stored, DEHP/PVC-free red blood cell units.
abstract: BACKGROUND
  Use of the plasticiser di(2-ethylhexyl) phthalate (DEHP) in polyvinyl chloride (PVC) blood bags poses a potential dilemma. The presence of DEHP in blood bags has been shown to be beneficial to red blood cells during storage by diminishing haemolysis. However, DEHP use in PVC may be carcinogenic or estrogenising. Vepoloxamer is a poloxamer with rheological and cytoprotective rheological properties and a favourable toxicity profile in clinical trials. We hypothesised that vepoloxamer may be sufficient to replace the plasticiser DEHP to prevent elevated haemolysis while conserving the biochemical and redox potential++ in RBCs stored for up to 42 days.
  
  
  METHODS
  Paired analyses of aliquots from pooled RBC suspensions of ABO identical donors were aseptically split into test storage containers (DEHP/PVC or DEHP-free/ethylene vinyl acetate [EVA]) supplemented with or without vepoloxamer (at concentrations of 0.1, 1, 5 or 7.89 mg/mL) and cold stored for up to 42 days.
  
  
  RESULTS
  Vepoloxamer significantly prevented the increased haemolysis induced by the absence of DEHP in EVA bags in a dose-dependent manner by days 28 and 42 of storage (approx. 50% reduction of the maximum concentration of vepoloxamer; p<0.001). There was an inverse correlation between the concentration of vepoloxamer used and the haemolysis rate (r2=0.27, p<0.001) and a direct correlation between haemolysis and phosphatidylserine (PS) exposure (r2=0.42; p<0.01). Increased osmotic fragility and shear induced deformability of 42-day stored RBC in EVA bags was significantly corrected by the addition of vepoloxamer.
  
  
  CONCLUSIONS
  Vepoloxamer, in a concentration-dependent fashion, is able to partly rescue the increased haemolysis and PS exposure induced by the absence of the commonly used plasticiser DEHP. These results provide initial but strong evidence to support vepoloxamer use to replace DEHP in long-term storage of RBC.
authors.affiliation: Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cancelas
authors.affiliation: Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Neeta
authors.initials: N
authors.lastname: Rugg
authors.affiliation: Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Shawnagay
authors.initials: S
authors.lastname: Nestheide
authors.affiliation: Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hill
authors.affiliation: Mast Therapeutics Inc., San Diego, CA, United States of America.
authors.forename: R Martin
authors.initials: RM
authors.lastname: Emanuele
authors.affiliation: Mast Therapeutics Inc., San Diego, CA, United States of America.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Mckenzie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001793:Blood Preservation / Q000379:methods*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D011143:Polyvinyl Chloride / Q000494:pharmacology*
chemical_list: D011092:Polyethylene Glycols; D011143:Polyvinyl Chloride; D004051:Diethylhexyl Phthalate