Salama A, Kroll H, Wittmann G, Mueller-Eckhardt C
Blutbank, Virchow-Klinikum der Humboldt-Universität zu Berlin, Germany.
Br J Haematol. 1996 Dec;95(4):640-4. doi: 10.1046/j.1365-2141.1996.d01-1947.x.
During the last 5 years we have identified a total of 17 patients (nine females and eight males aged between 53 and 85 years) with immune haemolytic anaemia related to diclofenac (a nonsteroidal anti-inflammatory drug). All patients developed acute intravascular haemolysis. Two patients died, and eight patients developed temporary renal failure that required haemodialysis. The direct antiglobulin test was positive with anti-IgG and anti-C3d in all cases, with anti-IgA in 4/10 cases tested, and negative with anti-IgM. The indirect antiglobulin test was moderately or weakly positive in 11 cases, and IgG autoantibodies could be eluted from the red blood cells (RBCs) of all patients. Initially, the diagnosis of autoimmune haemolytic anaemia of warm type was suggested in all cases. All patients had simultaneously developed autoantibodies and drug-dependent antibodies. The majority of drug-dependent antibodies (n = 13) reacted with urine containing the drug and its metabolites (ex vivo antigen), the native drug, and diclofenac-treated RBCs. The antibodies in the remaining four cases were detectable only in the presence of ex vivo antigen. Diclofenac appears to bind only weakly to RBCs in the absence of the drug-dependent antibodies. We conclude that diclofenac forms neoantigens with RBCs that may stimulate the production of autoantibodies and drug-dependent antibodies. The resulting haemolytic syndrome is very similar to autoimmune haemolytic anaemia of warm type.
在过去5年中，我们共确诊了17例与双氯芬酸（一种非甾体抗炎药）相关的免疫性溶血性贫血患者（9名女性和8名男性，年龄在53至85岁之间）。所有患者均发生急性血管内溶血。2例患者死亡，8例患者出现需要血液透析的暂时性肾衰竭。所有病例的直接抗球蛋白试验抗IgG和抗C3d均呈阳性，10例检测病例中有4例抗IgA呈阳性，抗IgM呈阴性。间接抗球蛋白试验在11例中呈中度或弱阳性，所有患者的红细胞（RBC）均可洗脱出血清IgG自身抗体。最初，所有病例均提示为温抗体型自身免疫性溶血性贫血。所有患者均同时产生自身抗体和药物依赖性抗体。大多数药物依赖性抗体（n = 13）与含有该药物及其代谢产物的尿液（体外抗原）、天然药物以及双氯芬酸处理的红细胞发生反应。其余4例中的抗体仅在存在体外抗原时才可检测到。在没有药物依赖性抗体的情况下，双氯芬酸似乎仅与红细胞弱结合。我们得出结论，双氯芬酸与红细胞形成新抗原，可能刺激自身抗体和药物依赖性抗体的产生。由此产生的溶血性综合征与温抗体型自身免疫性溶血性贫血非常相似。
