Abstract

After intravenous supplementation of an unintentionally high dose of the antioxidant alpha-lipoic acid (ALA), a 53-year-old female complained of myalgia, chills and nausea, and showed signs of haemorrhagic diathesis. The laboratory findings were excessive hyperferritinemia, leukoerythroblastosis, severe thrombocytopenia, elevated liver enzymes and impaired coagulation. The toxicological tests resulted in an ALA serum concentration of 10 280 µg/L. The peripheral blood film of the patient showed some neutrophil dysplasia with unusual small dark-blue stained round cytoplasmic inclusions resembling ‘Howell-Jolly-body-like’ (HJBL) cytoplasmic inclusions, aptly named due to the morphologic similarity to their erythrocytic counterparts. Such HJBL inclusions are occasionally associated with acquired immunodeficiency, or immunosuppressive or cytostatic treatment. An association with ALA intoxication has not been described before. There are only a few reports on unintentional, harmful and lethal intoxications with ALA. The underlying molecular background of its toxicity on liver function or haematopoiesis is not yet known in detail, but ALA seems to interact with enzyme functions, e.g. with mitochondrial enzyme-complexes, possibly due to its pro-oxidant potential at high doses.

摘要

一名 53 岁的女性在无意中静脉补充高剂量的抗氧化剂 α-硫辛酸 (ALA) 后，主诉肌痛、寒战和恶心，并出现出血素质的迹象。实验室检查结果是过度的高铁蛋白血症、白细胞增多症、严重的血小板减少症、肝酶升高和凝血功能受损。毒理学测试结果显示 ALA 血清浓度为 10 280 µg/L。患者的外周血涂片显示一些中性粒细胞发育不良，带有不寻常的小深蓝色染色圆形细胞质内含物，类似于“Howell-Jolly-body-like”（HJBL）细胞质内含物，因其与红细胞对应物的形态相似而得名。这种 HJBL 内含物偶尔与获得性免疫缺陷有关，或免疫抑制或细胞抑制治疗。以前没有描述过与 ALA 中毒的关联。只有少数关于 ALA 无意、有害和致命中毒的报告。其对肝功能或造血功能的毒性的潜在分子背景尚不清楚，但 ALA 似乎与酶功能相互作用，例如与线粒体酶复合物，可能是由于其在高剂量下的促氧化潜力。