Homberg J C
Laboratoire Central d'Immunologie et d'Hématologie, Hôpital Saint-Antoine, Paris.
Presse Med. 1999 Apr 3;28(13):703-8.
AUTOANTIBODY PRODUCTION: The production of autoantibodies can only occur if immune tolerance is circumvented. Thus drug-induced autoimmune hemolytic anemia requires that the drug have an effect on both autoantigens and on the immune system. AN EXAMPLE, METHYLDOPA: Methyldopa is a hypotensive agent which induces major production of anti-Rh IgG anti-erythrocyte autoantibodies, anti-nuclear antibodies and anti-actin antibodies. These autoantibodies generally appear 6 months after treatment onset and are observed in 20% of treated patients. Hemolysis is however exceptional and is only clinically or biologically perceptible in 1 to 2% of the patients who become immunized. Induced lupus has been reported as have been several dozen cases of drug-induced hepatitis with anti-actin autoantibodies. DRUGS INDUCING HEMOLYTIC ANEMIA: Besides methyldopa, other drugs known to induce hemolytic anemia include levodopa used for Parkinson's disease, mefenamic acid, a nonsteroidal antiinflammatory drug, interferon-alpha, used in chronic viral hepatitis, cyclosporin used for the prevention of graft rejection and the treatment of certain autoimmune diseases, and fludarabin, used in chronic lymphoid leukemia.
If there is no clinical or biological expression, the drug can be continued, excepting fludarabin where regular controls are needed. If hemolytic anemia is patent, the drug must be discontinued, transfusion and corticosteroid therapy should be envisaged.
自身抗体产生:只有在免疫耐受被规避时才会发生自身抗体的产生。因此,药物诱导的自身免疫性溶血性贫血要求药物对自身抗原和免疫系统都有作用。一个例子,甲基多巴:甲基多巴是一种降压药,可诱导大量产生抗Rh IgG抗红细胞自身抗体、抗核抗体和抗肌动蛋白抗体。这些自身抗体通常在治疗开始后6个月出现,在20%的接受治疗的患者中可观察到。然而,溶血情况罕见,在产生免疫的患者中只有1%至2%在临床或生物学上可察觉。已报告有药物诱导的狼疮以及几十例伴有抗肌动蛋白自身抗体的药物性肝炎病例。诱导溶血性贫血的药物:除甲基多巴外,已知可诱导溶血性贫血的其他药物包括用于帕金森病的左旋多巴、非甾体抗炎药甲芬那酸、用于慢性病毒性肝炎的α干扰素、用于预防移植排斥和治疗某些自身免疫性疾病的环孢素以及用于慢性淋巴细胞白血病的氟达拉滨。
如果没有临床或生物学表现,除氟达拉滨需要定期监测外,药物可以继续使用。如果溶血性贫血明显,必须停用药物,并应考虑输血和皮质类固醇治疗。