Cancelas Jose A, Rugg Neeta, Nestheide Shawnagay, Hill Sarah E, Emanuele R Martin, Mckenzie Douglas S
Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH, United States of America.
Mast Therapeutics Inc., San Diego, CA, United States of America.
Blood Transfus. 2017 Mar;15(2):165-171. doi: 10.2450/2017.0351-16.
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.
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.
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 (r=0.27, p<0.001) and a direct correlation between haemolysis and phosphatidylserine (PS) exposure (r=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.
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.
在聚氯乙烯(PVC)血袋中使用增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)存在潜在难题。血袋中DEHP的存在已被证明在储存期间对红细胞有益,可减少溶血。然而,PVC中使用DEHP可能具有致癌性或雌激素样作用。维泊洛沙姆是一种具有流变学和细胞保护流变学特性且在临床试验中具有良好毒性特征的泊洛沙姆。我们假设维泊洛沙姆可能足以替代增塑剂DEHP,以防止溶血增加,同时保持储存长达42天的红细胞中的生化和氧化还原电位。
将来自ABO血型相同供者的混合红细胞悬液的等分试样进行配对分析,无菌分装到补充或未补充维泊洛沙姆(浓度为0.1、1、5或7.89 mg/mL)的测试储存容器(DEHP/PVC或无DEHP/乙烯-醋酸乙烯酯[EVA])中,并冷藏长达42天。
在储存第28天和第42天时,维泊洛沙姆以剂量依赖的方式显著预防了EVA袋中因缺乏DEHP而导致的溶血增加(维泊洛沙姆最大浓度降低约50%;p<0.001)。所用维泊洛沙姆浓度与溶血率呈负相关(r=0.27,p<0.001),溶血与磷脂酰丝氨酸(PS)暴露呈正相关(r=0.42;p<0.01)。添加维泊洛沙姆可显著纠正EVA袋中储存42天的红细胞增加的渗透脆性和剪切诱导变形性。
维泊洛沙姆能够以浓度依赖的方式部分挽救因缺乏常用增塑剂DEHP而导致的溶血增加和PS暴露。这些结果提供了初步但有力的证据,支持在红细胞长期储存中使用维泊洛沙姆替代DEHP。