Bairstow Shawn, McKee Jeff, Nordhaus Mark, Johnson Richard
Technology Resources, Baxter Healthcare, 25212 W. Illinois Rt 120, Round Lake, IL 60073, USA.
Anal Biochem. 2009 May 15;388(2):317-21. doi: 10.1016/j.ab.2009.03.009. Epub 2009 Mar 14.
Heparin is a commonly implemented anticoagulant used to treat critically ill patients. Recently, a number of commercial lots of heparin products were found to be contaminated with an oversulfated chondroitin sulfate (OSCS) derivative that could elicit a hypotensive response in pigs following a single high-dose infusion. Using both contaminated heparin products and the synthetically produced derivative, we showed that the OSCS produces dose-dependent hypotension in pigs. The no observed effect level (NOEL) for this contaminant appears to be approximately 1mg/kg, corresponding to a contamination level of approximately 3%. We also demonstrated that OSCS can be identified in heparin products using a simple, inexpensive, commercially available heparin enzyme immunoassay (EIA) kit that has a limit of detection of approximately 0.1%, well below the NOEL. This kit may provide a useful method to test heparin products for contamination with oversulfated GAG derivatives.
肝素是一种常用于治疗重症患者的抗凝剂。最近，发现许多商业批次的肝素产品被一种过度硫酸化的硫酸软骨素（OSCS）衍生物污染，该衍生物在猪单次高剂量输注后可引发低血压反应。使用受污染的肝素产品和合成生产的衍生物，我们表明OSCS在猪中产生剂量依赖性低血压。这种污染物的未观察到效应水平（NOEL）似乎约为1mg/kg，相当于约3%的污染水平。我们还证明，使用一种简单、廉价、可商购的肝素酶免疫测定（EIA）试剂盒可以在肝素产品中鉴定出OSCS，该试剂盒的检测限约为0.1%，远低于NOEL。该试剂盒可能为检测肝素产品是否被过度硫酸化的糖胺聚糖衍生物污染提供一种有用的方法。
