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Autoimmune haemolytic anaemias

Nature Reviews Disease Primers volume 10, Article number: 82 (2024) Cite this article

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Abstract

Adult autoimmune haemolytic anaemias (AIHAs) include different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on the membrane of autologous red blood cells (RBCs) are produced, leading to their accelerated destruction. In the presence of haemolytic anaemia, the direct antiglobulin test is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, the most frequent type of AIHAs, are associated with underlying conditions in ~50% of cases. In wAIHA, IgG autoantibody reacts with autologous RBCs at 37 °C, leading to antibody-dependent cell-mediated cytotoxicity and increased phagocytosis of RBCs in the spleen. Cold AIHAs include cold agglutinin disease (CAD) and cold agglutinin syndrome (CAS) when there is an underlying condition. CAD and cold agglutinin syndrome are IgM cold antibody-driven AIHAs characterized by classical complement pathway-mediated haemolysis. The management of wAIHAs has long been based around corticosteroids and splenectomy and on symptomatic measures and non-specific cytotoxic agents for CAD. Rituximab and the development of complement inhibitors, such as the anti-C1s antibody sutimlimab, have changed the therapeutic landscape of AIHAs, and new promising targeted therapies are under investigation.

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Fig. 1: Pathophysiology of warm adult autoimmune haemolytic anaemias.
Fig. 2: Pathophysiology of CAD.
Fig. 3: Diagnostic procedure for AIHA.
Fig. 4: Treatment algorithm for primary wAIHA and CAD.

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Authors and Affiliations

  1. Department of Internal Medicine and Clinical Immunology, National Reference Centre for Adult Immune Cytopenias, Henri Mondor University Hospital, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France

    Marc Michel & Etienne Crickx

  2. Hematology Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Bruno Fattizzo & Wilma Barcellini

  3. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Bruno Fattizzo

Authors
  1. Marc Michel
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  2. Etienne Crickx
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  3. Bruno Fattizzo
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  4. Wilma Barcellini
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Contributions

Introduction (M.M.); Epidemiology (B.F.); Mechanisms/pathophysiology (E.C.); Diagnosis, screening and prevention (W.B.); Management (M.M.); Quality of life (B.F.); Outlook (M.M.).

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Correspondence to Marc Michel.

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Competing interests

M.M. has received consultancy or advisory board honoraria and speaker’s bureau from Alexion, Amgen, Grifols, Johnson and Johnson Novartis, Sanofi, Sobi and UCB. E.C. has received honoraria (advisory boards, speaker fees) from Novartis, UCB and Sanofi. W.B. has received consultancy or  advisory board honoraria for Agios, Alexion, Amgen, Incyte, Novartis, Roche, Sanofi and SOBI; has received lecture fees or congress support from Alexion, Amgen, Novartis and Sanofi; and has received research support from Alexion. B.F. has received consultancy or advisory board honoraria and speaker’s bureau from Agios, Alexion, Apellis, Janssen, Novartis, Roche, Samsung, Sanofi and Sobi.

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Nature Reviews Disease Primers thanks J. W. Jacobs, D. L. Hansen, S. S. Datta, M. Miano and B. Mayer for their contribution to the peer review of this work.

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Michel, M., Crickx, E., Fattizzo, B. et al. Autoimmune haemolytic anaemias. Nat Rev Dis Primers 10, 82 (2024). https://doi.org/10.1038/s41572-024-00566-2

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