Severe autoimmune hemolytic anemia; epidemiology, clinical management, outcomes and knowledge gaps

Femke V M Mulder; Dorothea Evers; Masja de Haas; Marjan J Cruijsen; Sophie J Bernelot Moens; Wilma Barcellini; Bruno Fattizzo; Josephine M I Vos

doi:10.3389/fimmu.2023.1228142

Severe autoimmune hemolytic anemia; epidemiology, clinical management, outcomes and knowledge gaps

Front Immunol. 2023 Sep 18:14:1228142. doi: 10.3389/fimmu.2023.1228142. eCollection 2023.

Authors

Femke V M Mulder^{1

2}, Dorothea Evers³, Masja de Haas^{1

2

4}, Marjan J Cruijsen⁵, Sophie J Bernelot Moens⁶, Wilma Barcellini⁷, Bruno Fattizzo^{7

8}, Josephine M I Vos^{4

6}

Affiliations

¹ Sanquin Research and Landsteiner Laboratory, Translational Immunohematology, Amsterdam UMC, Amsterdam, Netherlands.
² Department of Hematology, Leiden University Medical Center, Leiden, Netherlands.
³ Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands.
⁴ Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Amsterdam, Netherlands.
⁵ Department of Hematology, Catharina Hospital, Eindhoven, Netherlands.
⁶ Department of Hematology and Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
⁷ Department of Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁸ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

Abstract

Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder, mediated by auto-antibodies, and has a variable clinical course ranging from fully compensated low grade hemolysis to severe life-threatening cases. The rarity, heterogeneity and incomplete understanding of severe AIHA complicate the recognition and management of severe cases. In this review, we describe how severe AIHA can be defined and what is currently known of the severity and outcome of AIHA. There are no validated predictors for severe clinical course, but certain risk factors for poor outcomes (hospitalisation, transfusion need and mortality) can aid in recognizing severe cases. Some serological subtypes of AIHA (warm AIHA with complement positive DAT, mixed, atypical) are associated with lower hemoglobin levels, higher transfusion need and mortality. Currently, there is no evidence-based therapeutic approach for severe AIHA. We provide a general approach for the management of severe AIHA patients, incorporating monitoring, supportive measures and therapeutic options based on expert opinion. In cases where steroids fail, there is a lack of rapidly effective therapeutic options. In this era, numerous novel therapies are emerging for AIHA, including novel complement inhibitors, such as sutimlimab. Their potential in severe AIHA is discussed. Future research efforts are needed to gain a clearer picture of severe AIHA and develop prediction models for severe disease course. It is crucial to incorporate not only clinical characteristics but also biomarkers that are associated with pathophysiological differences and severity, to enhance the accuracy of prediction models and facilitate the selection of the optimal therapeutic approach. Future clinical trials should prioritize the inclusion of severe AIHA patients, particularly in the quest for rapidly acting novel agents.

Keywords: autoimmune hemolytic anemia; cold agglutinin disease; management; mortality; severe.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Anemia, Hemolytic, Autoimmune* / diagnosis
Anemia, Hemolytic, Autoimmune* / epidemiology
Anemia, Hemolytic, Autoimmune* / therapy
Blood Transfusion
Disease Progression
Hemolysis
Humans
Steroids / therapeutic use

Substances

Steroids

Grants and funding

The authors declare that this study received funding from Sanquin Diagnostics B.V. Unit Healthcare. Grant number PPO-SHS-2022-22.13/L2687. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.