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补骨脂素介导的血小板浓缩物光净化:人免疫缺陷病毒无细胞形式和细胞相关形式的灭活及体内血小板功能评估

Psoralen-mediated photodecontamination of platelet concentrates: inactivation of cell-free and cell-associated forms of human immunodeficiency virus and assessment of platelet function in vivo.

作者信息

Margolis-Nunno H, Bardossy L, Robinson R, Ben-Hur E, Horowitz B, Blajchman M A

机构信息

New York Blood Center and V.I. Technologies, Inc., New York, USA.

出版信息

Transfusion. 1997 Sep;37(9):889-95. doi: 10.1046/j.1537-2995.1997.37997454013.x.

Abstract

BACKGROUND

Treatment of platelet concentrates (PCs) with psoralens and broad-band ultraviolet A (UVA) radiation is being examined for the elimination of pathogens that might be present in donated blood. Previous studies have demonstrated the inactivation of cell-free viruses and the maintenance of platelet integrity with common in vitro assays.

STUDY DESIGN AND METHODS

Human immunodeficiency virus (HIV) in three forms-cell-free, activity replicating, and latently infected cell lines-was added to PCs and treated with 50-microgram per mL of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), 0.35 mM rutin, and broad- and narrow-band UVA light (320-400 nm and 360-370 nm [UVA1], respectively). The inactivation of added HIV was assessed in tissue culture; platelet hemostatic activity was assessed in thrombocytopenic rabbits.

RESULTS

Each form of HIV was inactivated completely (> or = 10(5) infectious units) on treatment with 30 J per cm2 of UVA1 light. Similar results were obtained on treatment of 2.5 mL of PCs in test tubes or intact PC units (50 mL) in blood bags. Latently infected cell lines were substantially more sensitive than cell-free HIV or HIV that was actively replicating. Human platelets treated with 40 J per cm2 of UVA1 light had a fully corrected bleeding time shortly after treatment or after 5 days' storage, as assessed in thrombocytopenic rabbits. Platelet hemostatic function began to decrease with 81 J per cm2 of UVA1 light and was abolished with 113 J per cm2. At similar fluences, broad-band UVA light was more injurious to platelets than was UVA1 light.

CONCLUSION

HIV transmission might be eliminated by PCs after treatment with AMT and UVA1 light and without a reduction in platelet hemostatic function.

摘要

背景

正在研究用补骨脂素和宽带紫外线A(UVA)辐射处理血小板浓缩物(PCs),以消除献血中可能存在的病原体。先前的研究已通过常见的体外试验证明了无细胞病毒的灭活以及血小板完整性的维持。

研究设计与方法

将三种形式的人类免疫缺陷病毒(HIV)——无细胞的、活性复制的和潜伏感染的细胞系——添加到PCs中,并用每毫升50微克的4'-氨甲基-4,5',8-三甲基补骨脂素(AMT)、0.35毫摩尔芦丁以及宽带和窄带UVA光(分别为320 - 400纳米和360 - 370纳米[UVA1])进行处理。在组织培养中评估添加的HIV的灭活情况;在血小板减少的兔子中评估血小板止血活性。

结果

用每平方厘米30焦的UVA1光处理后,每种形式的HIV均被完全灭活(≥10⁵感染单位)。在试管中处理2.5毫升PCs或血袋中的完整PC单位(50毫升)时也获得了类似结果。潜伏感染的细胞系比无细胞HIV或活性复制的HIV敏感得多。在血小板减少的兔子中评估,用每平方厘米40焦的UVA1光处理的人血小板在处理后或储存5天后出血时间完全恢复正常。当UVA1光剂量达到每平方厘米81焦时,血小板止血功能开始下降,达到每平方厘米113焦时则完全丧失。在相同辐照量下,宽带UVA光对血小板的损伤比UVA1光更大。

结论

用AMT和UVA1光处理后的PCs可能消除HIV传播,且不会降低血小板止血功能。

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