Horowitz B, Bonomo R, Prince A M, Chin S N, Brotman B, Shulman R W
New York Blood Center, New York 10021.
Blood. 1992 Feb 1;79(3):826-31.
Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by-product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.
新鲜冰冻血浆（FFP）在世界各地的血库中作为红细胞浓缩液制备的副产品而制备。其适当的临床用途是用于凝血因子紊乱，在没有合适的浓缩物时以及在手术等出现多种凝血因子缺乏的情况下使用。病毒安全性取决于献血者的选择和筛查；因此，与全血一样，仍存在虽小但明确的病毒传播风险。我们通过在30℃下用1%磷酸三（正丁基）酯（TNBP）和1% Triton X - 100处理FFP 4小时来制备病毒灭活FFP（S/D - FFP）。添加的试剂通过用大豆油萃取和在不溶性C18树脂上进行色谱分离来去除。该处理导致水泡性口炎病毒（VSV）大于或等于10(⁷.⁵)感染剂量（ID50）、辛德毕斯病毒（用作标记病毒）大于或等于10(⁶.⁹) ID50、人类免疫缺陷病毒（HIV）大于或等于10(⁶.²) ID50、乙型肝炎病毒（HBV）大于或等于10(⁶)黑猩猩感染剂量（CID50）以及丙型肝炎病毒（HCV）大于或等于10(⁵) CID50迅速且完全失活。用S/D - FFP免疫兔子并随后用未处理的FFP吸附产生的抗体，证实没有新免疫原形成。凝血因子含量与FFP中的相当。基于这些实验室和动物研究，以及S/D处理的凝血因子浓缩物成功使用的广泛历史，我们得出结论，在生产设施中制备的S/D - FFP替代FFP将提高病毒安全性和产品一致性，且不会损失疗效。
