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15 例奥沙利铂致药物性免疫性溶血性贫血患者的血清学特征。

Serologic characteristics of oxaliplatin antibodies in 15 patients with drug-induced immune hemolytic anemia.

机构信息

Etablissement Français du Sang, Laboratoire de Biologie Médicale, Site Saint-Antoine, Paris, France.

Etablissement Français du Sang, Laboratoire de Biologie Médicale, Site Ivry, 122-130 rue Marcel Hartmann, 94200 Ivry-sur-Seine, France.

出版信息

Transfusion. 2021 May;61(5):1609-1616. doi: 10.1111/trf.16360. Epub 2021 Mar 13.

DOI:10.1111/trf.16360
PMID:33686704
Abstract

BACKGROUND

Oxaliplatin, a third-generation platinum derivative is commonly used in combination treatment of metastatic colorectal cancer. Since 2008, it is the second most common cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our laboratory.

STUDY DESIGN AND METHODS

Samples from fifteen patients including nine (60%) with intravascular hemolysis, suspected of having DIIHA were studied for the presence of anti-oxaliplatin. Direct antiglobulin tests (DATs) and tests with oxaliplatin-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs in the presence of oxaliplatin were performed. A pool of normal AB sera with no unexpected antibodies was used as a control for nonimmunologic protein adsorption (NIPA).

RESULTS

Eleven (73%) of the fifteen patients had antibodies to oxaliplatin that reacted with drug-treated RBCs and untreated RBCs in the presence of drug by tube and/or gel method. Lower-titer reactivity (<20) obtained with four patients' sera and the corresponding pooled normal sera was most likely due to NIPA. Eighty seven percent (13/15) of the patients had positive DAT either with anti-IgG only (33%), IgG + C3d (40%), or C3d only (13%). Two patients had a negative DAT. No directly agglutinating antibody was observed with the pools of normal donor's sera in the presence of oxaliplatin.

CONCLUSION

Anti-oxaliplatin can cause severe intravascular hemolysis. Complement can usually be detected on the patient's RBCs and anti-oxaliplatin can be detected in the patient's serum. RBC-bound albumin detection with anti-human albumin needs to be performed to confirm NIPA which could have contributed to the patient's hemolytic anemia.

摘要

背景

奥沙利铂是第三代铂类衍生物,常用于转移性结直肠癌的联合治疗。自 2008 年以来,它是我们实验室研究的第二大药物诱导免疫性溶血性贫血(DIIHA)的常见原因。

研究设计和方法

研究了包括 9 例(60%)血管内溶血在内的 15 例疑似 DIIHA 患者样本,以检测抗奥沙利铂。进行了直接抗球蛋白试验(DAT)和奥沙利铂处理的红细胞(RBC)或未经处理和酶处理的 RBC 在奥沙利铂存在下的试验。使用无意外抗体的正常 AB 血清池作为非免疫性蛋白吸附(NIPA)的对照。

结果

15 例患者中有 11 例(73%)的血清中存在针对奥沙利铂的抗体,这些抗体通过试管和/或凝胶法与药物处理的 RBC 和未经药物处理的 RBC 发生反应。4 例患者血清和相应的正常血清池获得的低滴度反应(<20)很可能是由于 NIPA。15 例患者中有 87%(13/15)的 DAT 阳性,要么只有抗 IgG(33%),要么 IgG+C3d(40%),要么只有 C3d(13%)。有 2 例患者 DAT 阴性。在奥沙利铂存在下,正常供体血清池未观察到直接凝集抗体。

结论

抗奥沙利铂可引起严重的血管内溶血。患者的 RBC 上通常可检测到补体,患者的血清中可检测到抗奥沙利铂。需要进行抗人白蛋白检测以确认 NIPA,NIPA 可能导致患者溶血性贫血。

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