Sanford-Driscoll M, Knodel L C
Drug Intell Clin Pharm. 1986 Dec;20(12):925-34. doi: 10.1177/106002808602001202.
The incidence of immune hemolytic anemia (IHA) is increasing. The proliferation of pharmaceuticals is a contributing factor to this increase. IHA is an uncommon, though significant, adverse effect of a wide variety of drugs. Several recent case reports have implicated the nonsteroidal antiinflammatory drugs (NSAIDs). Because of the extensive use of this class of drugs, a review of case reports, clinical studies, and in vitro research was conducted on NSAID-induced IHA. Mefenamic acid, ibuprofen, sulindac, naproxen, tolmetin, feprazone, and aspirin are reported to cause IHA, with mefenamic acid most frequently implicated. Mefenamic acid appears to cause hemolytic anemia by an autoimmune mechanism similar to methyldopa and aspirin by an immune complex mechanism. However, there is insufficient information concerning ibuprofen, sulindac, naproxen, tolmetin, and feprazone to assign specific mechanisms of immune hemolysis. In individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, aspirin at usual therapeutic doses is not a predisposing factor to hemolysis unless other risk factors are present. Although individuals with G-6-PD deficiency are at increased risk of developing hemolytic anemia when exposed to oxidizing stresses, the use of NSAIDs does not appear to increase this risk significantly. Because NSAID-induced IHA occurs infrequently and the sensitivity of currently used tests to detect drug-dependent antibodies is limited, routine serologic testing in patients receiving NSAIDs is not justified. If hemolytic anemia occurs in a NSAID-treated patient and the history is consistent with a drug-induced etiology, the NSAID should be discontinued. With discontinuation of the offending agent, the prognosis is good. There is a rapid hematologic recovery, with a slow resolution of abnormal serologic findings.
免疫性溶血性贫血（IHA）的发病率正在上升。药物种类的增多是导致这一上升趋势的一个因素。IHA是多种药物罕见但严重的不良反应。最近的几例病例报告已将非甾体抗炎药（NSAIDs）列为病因。由于这类药物的广泛使用，因此针对NSAIDs诱发的IHA，对病例报告、临床研究和体外研究进行了综述。据报道，甲芬那酸、布洛芬、舒林酸、萘普生、托美丁、非普拉宗和阿司匹林可导致IHA，其中甲芬那酸最常被提及。甲芬那酸似乎通过类似于甲基多巴的自身免疫机制导致溶血性贫血，而阿司匹林则通过免疫复合物机制致病。然而，关于布洛芬、舒林酸、萘普生、托美丁和非普拉宗，尚无足够信息来确定其免疫溶血的具体机制。在葡萄糖-6-磷酸脱氢酶（G-6-PD）缺乏的个体中，除非存在其他危险因素，否则常规治疗剂量的阿司匹林并非溶血的诱发因素。虽然G-6-PD缺乏的个体在暴露于氧化应激时发生溶血性贫血的风险增加，但使用NSAIDs似乎并不会显著增加这一风险。由于NSAIDs诱发的IHA很少发生，且目前使用的检测方法检测药物依赖性抗体的灵敏度有限，因此对接受NSAIDs治疗的患者进行常规血清学检测并无必要。如果NSAIDs治疗的患者发生溶血性贫血，且病史与药物诱发病因相符，则应停用NSAIDs。停用致病药物后，预后良好。血液学指标迅速恢复，血清学异常结果则缓慢消退。
