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Peer-reviewedCC BY 4.0Frontiers in Immunology

Clinical characteristics, treatment patterns and long-term outcomes of warm and mixed autoimmune hemolytic anemia: insights from a real-world study

  1. 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
  2. 2Tianjin Institutes of Health Science

Abstract

Objective: Autoimmune hemolytic anemia (AIHA) represents a heterogeneous group of autoimmune disorders, with limited large-scale real-world evidence from Asian populations. This study aimed to characterize the clinical characteristics, treatment patterns, and long-term outcomes of patients with warm AIHA (wAIHA) and mixed AIHA (mAIHA).

Methods: This single-center retrospective study screened 629 patients with AIHA hospitalized in China between 2014 and 2023. After excluding 32 patients with cold AIHA and 31 with DAT-negative AIHA, 566 patients (449 wAIHA and 117 mAIHA) were included, with a median follow-up of 57 months.

Results: Compared with wAIHA, mAIHA patients presented with earlier onset, poorer bone marrow compensation, and cold AIHA-like features despite comparable hemoglobin levels. Secondary AIHA was more prevalent in mAIHA (39.3% vs. 22.5%). Glucocorticoids remained the first-line treatment with similar response rates in both subtypes, while rituximab was the predominant second-line therapy. Treatment strategies and outcomes with multiple emerging therapies were also summarized. Median event-free survival was 17 months, with relapses mainly occurring during treatment tapering or infections. Estimated overall survival (OS) rates at 1, 3, and 5 years were 96%, 92%, and 89%, respectively, with infections and disease progression being leading causes of mortality. Independent risk factors associated with OS included age ≥60, hemoglobin at onset <6 g/dL, bone marrow responsiveness index <121, male sex, and an IgM+IgA-mediated serological pattern, whereas cold agglutinin titers demonstrated limited value in predicting OS or treatment response.

Conclusions: mAIHA and wAIHA share comparable glucocorticoid response and long-term survival despite distinct clinical and serological characteristics. This large real-world cohort delineates the profiles of wAIHA and mAIHA and identifies baseline factors associated with OS to support individualized management. Emerging therapies present promising prospects in AIHA management.

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BibTeX
@article{zhang2026clinical,
  title = {{Clinical characteristics, treatment patterns and long-term outcomes of warm and mixed autoimmune hemolytic anemia: insights from a real-world study}},
  author = {Junan Zhang and Yuan Li and Jiewen Qiu and Yizhou Zheng and Meili Ge and Fengkui Zhang and Jun Shi and Xin Zhao},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1931581},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931581/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Clinical characteristics, treatment patterns and long-term outcomes of warm and mixed autoimmune hemolytic anemia: insights from a real-world study
AU  - Junan Zhang
AU  - Yuan Li
AU  - Jiewen Qiu
AU  - Yizhou Zheng
AU  - Meili Ge
AU  - Fengkui Zhang
AU  - Jun Shi
AU  - Xin Zhao
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1931581
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931581/full
AB  - Objective: Autoimmune hemolytic anemia (AIHA) represents a heterogeneous group of autoimmune disorders, with limited large-scale real-world evidence from Asian populations. This study aimed to characterize the clinical characteristics, treatment patterns, and long-term outcomes of patients with warm AIHA (wAIHA) and mixed AIHA (mAIHA).  Methods: This single-center retrospective study screened 629 patients with AIHA hospitalized in China between 2014 and 2023. After excluding 32 patients with cold AIHA and 31 with DAT-negative AIHA, 566 patients (449 wAIHA and 117 mAIHA) were included, with a median follow-up of 57 months.  Results: Compared with wAIHA, mAIHA patients presented with earlier onset, poorer bone marrow compensation, and cold AIHA-like features despite comparable hemoglobin levels. Secondary AIHA was more prevalent in mAIHA (39.3% vs. 22.5%). Glucocorticoids remained the first-line treatment with similar response rates in both subtypes, while rituximab was the predominant second-line therapy. Treatment strategies and outcomes with multiple emerging therapies were also summarized. Median event-free survival was 17 months, with relapses mainly occurring during treatment tapering or infections. Estimated overall survival (OS) rates at 1, 3, and 5 years were 96%, 92%, and 89%, respectively, with infections and disease progression being leading causes of mortality. Independent risk factors associated with OS included age ≥60, hemoglobin at onset <6 g/dL, bone marrow responsiveness index <121, male sex, and an IgM+IgA-mediated serological pattern, whereas cold agglutinin titers demonstrated limited value in predicting OS or treatment response.  Conclusions: mAIHA and wAIHA share comparable glucocorticoid response and long-term survival despite distinct clinical and serological characteristics. This large real-world cohort delineates the profiles of wAIHA and mAIHA and identifies baseline factors associated with OS to support individualized management. Emerging therapies present promising prospects in AIHA management.
SN  - 1664-3224
ER  -