自身免疫性溶血性贫血:诊断和治疗的挑战。

IF 1.9 4区 医学 Q3 HEMATOLOGY
Transfusion Medicine and Hemotherapy Pub Date : 2024-08-27 eCollection Date: 2024-10-01 DOI:10.1159/000540475
Wilma Barcellini, Bruno Fattizzo
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引用次数: 0

摘要

背景:自身免疫性溶血性贫血(AIHA)是一种罕见疾病:摘要:根据自身抗体的同种型和热振幅,AIHA通常分为温性AIHA(wAIHA)和冷凝集素病(CAD)。直接抗球蛋白试验(DAT)或库姆斯试验(Coombs test)是诊断 AIHA 的基石,因为在 wAIHA 中抗 IgG 呈阳性,而在 CAD 中抗 C3d/IgM 抗血清加高滴度冷凝集素呈阳性。治疗方法也大不相同,前者使用类固醇和利妥昔单抗有效,而后者的反应率和持续时间都较短。脾切除术对于年轻/健康的 wAIHA 患者来说仍然是一个不错的选择,但对于 CAD 患者则是禁忌症,传统的免疫抑制剂正在向更深层次发展。一些新药正越来越多地用于复发/难治性AIHA,或正在试验中,包括B细胞(parsaclisib、ibrutinib、ritzabrutinib)和浆细胞靶向疗法(硼替佐米、达拉曲单抗)、双嘧达莫(bispisomab)等、daratumumab)、双特异性药物(iaalumab、obexelimab、povetacicept)、新生儿 Fc 受体阻断剂(nipocalimab)和补体抑制剂(sutimlimab、ritiprubart、pegcetacoplan、iptacopan)。在临床上,AIHA 的类型多种多样,从轻度/代偿性到危及生命/终末性,可能是原发性的,也可能与感染、肿瘤、自身免疫性疾病、移植、免疫缺陷和药物有关。除了所有这些变数外,还有一些罕见的类型,如混合型(wAIHA 加 CAD)、非典型(IgA 或温 IgM 驱动型)和 DAT 阴性,这些类型的诊断和临床治疗尤其具有挑战性:本文涵盖了 wAIHA 和 CAD 的经典临床特征、诊断和治疗,并通过临床案例重点介绍了需要新型疗法的疑难诊断和难治/复发病例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy.

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation.

Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging.

Key messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies.

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来源期刊
CiteScore
4.00
自引率
9.10%
发文量
47
审稿时长
6-12 weeks
期刊介绍: This journal is devoted to all areas of transfusion medicine. These include the quality and security of blood products, therapy with blood components and plasma derivatives, transfusion-related questions in transplantation, stem cell manipulation, therapeutic and diagnostic problems of homeostasis, immuno-hematological investigations, and legal aspects of the production of blood products as well as hemotherapy. Both comprehensive reviews and primary publications that detail the newest work in transfusion medicine and hemotherapy promote the international exchange of knowledge within these disciplines. Consistent with this goal, continuing clinical education is also specifically addressed.
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