藥物誘導免疫溶血性貧血文獻回顧及臨床診斷探討

藥物誘導免疫溶血性貧血(Drug-induced immune hemolytic anemia, DIIHA)屬於罕見的藥物不良反應(Adverse drug reaction, ADR)，臨床個案表現可能是輕微或急性嚴重的溶血性貧血，因此常被忽略或誤診。此研究目的為，介紹與DIIHA相關的藥物種類、藥物抗體產生的免疫機制以及實驗室進行鑑別診斷的流程，期望為DIIHA的臨床管理提供一份可參考的相關資料或建議。本研究收集PubMed、Google scholar及網路資料庫中的DIIHA相關文獻後，仔細閱讀後整理介紹已經發表的報導，內容包含可促使DIIHA的藥物及其臨床相關的檢驗項目與血清學特徵。研究結果為整合已經發表證實與DIIHA相關的100多種藥物清單供臨床參考查閱，並繪製實驗室鑑定相關免疫溶血性貧血的流程圖提示調查DIIHA的完整思路。DIIHA的發生主要歸因於藥物抗體的產生，而根據檢測的方法可以將藥物抗體分成兩大類：「藥物依賴性抗體」即在體外的實驗需加入藥物才能與紅血球反應。「藥物非依賴性抗體」即不需藥物存在也能與紅血球反應。另外，整理出部分特殊藥物會修飾紅血球細胞膜，造成血漿中的蛋白質非免疫性的吸附而形成溶血的相關研究。研究總結論為，與DIIHA相關的藥物逐年增加，需具備DIIHA臨床表現和實驗室輔助診斷的知識才可以正確的加以診斷。確診DIIHA的病人應進行ADR通報並建立檔案，才可避免再次發生提升病人用藥安全。

關鍵字

藥物誘導免疫溶血性貧血；藥物不良反應；藥物依賴性抗體；藥物非依賴性抗體

並列摘要

Drug-induced immune hemolytic anemia (DIIHA) is a rare adverse drug reaction (ADR). The clinical case may be mild or acute severe hemolytic anemia, which is usually disregard or misdiagnosed. The purpose of this study is to introduce drugs related to DIIHA, the immune mechanism of drug antibody production and making a differential diagnosis process in the laboratory, which provide recommendations for the clinical management of DIIHA. After collecting and reading the DIIHA-related literature reports in PubMed, Scholar, and the online database, we will summarize and introduce the drugs that have caused DIIHA and related clinical and serological research results. The results show that about currently more than 100 drugs are confirmed to be related to DIIHA. And draw a flowchart of laboratory identification of immune hemolytic anemia, prompting the complete idea of investigating DIIHA. According to the detection method, antibodies of drugs can be divided into two categories: the "Drug dependent antibodies, DDABs" category, in vitro the experiments require to add drugs to react with red blood cells (RBCs). The "Drug-independent antibodies, DIABs" category, the experiments can react with red blood cells without the presence of drugs. On the other wide, some special drugs can modify RBC membranes, causing non-immunologic protein adsorption onto drug-treated RBCs and may causing hemolysis. Finally, the conclusion of this study are more and more drugs involved in DIIHA, and the correctly diagnosis of DIIHA is required good understanding of clinical manifestations and laboratory-assisted tests. The recommendation of this study is report of patients diagnosed with DIIHA should be notified and filed to avoid recurrence of ADR to improve patient safety.