Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events
Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events
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DOI：
10.1038/nbt1407
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发表时间：
2008-06-01
影响因子：
46.9
通讯作者：
Sasisekharan, Ram
中科院分区：
文献类型：
--
作者：
Guerrini, Marco;Beccati, Daniela;Sasisekharan, Ram
最近，某些批次的肝素与急性、快速发作的严重副作用相关，提示过敏型反应。为了确定这种副作用突然增加的潜在原因，我们使用正交高分辨率分析技术检查了大量与不良事件相关的肝素。通过详细的结构分析，发现污染物含有葡萄糖醛酸的二糖重复单元，其连接β 1 -> 3至β-N-乙酰半乳糖胺。二糖单元具有不寻常的硫酸化模式，在葡萄糖醛酸的2-O和3-O位置以及半乳糖胺的4-O和6-O位置硫酸化。鉴于这种污染物的性质，传统的筛选试验无法区分受影响和未受影响的批次。我们的分析表明，有效的筛选方法，可用于确定是否肝素批次含有污染物在这里报告。
Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta 1 -> 3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.