Background: Warm autoimmune haemolytic anaemia (wAIHA) is rare but associated with significant mortality, morbidity, and treatment-related complications. There is limited Australian data on the incidence, burden of disease, and treatment outcomes.

Aims: We propose to report on the epidemiology and clinical characteristics, treatment and outcomes in a real-world retrospective audit of wAIHA cases in a regional Australian tertiary referral centre.

Methods: We performed a single-centre retrospective audit of wAIHA diagnosed between 01/01/2018- 11/11/2022 by collecting all positive direct antiglobulin tests (DAT) reported in the Australian Capital Territory (ACT) Pathology during this period. Then, investigators reviewed case records and laboratory data to determine whether a clinical diagnosis of wAIHA was established and their outcomes. Cold agglutinin disease was excluded. Descriptive statistics were performed with medians and interquartile ranges reported.

Results: The annual incidence of new wAIHA over this period was 2.1 per 100,000 per year (Australian Bureau of Statistics, based on the population of the ACT). There were 1356 DATs performed, including 772 unique patients who have undergone testing among which 46 cases of wAIHA were identified.

There was a male preponderance (60.9%), and the median age at diagnosis was 70.8 (57.5-78.9) years. At presentation, the median haemoglobin (Hb) was 73 (55-81) g/L, LDH 506 (332.8-704.8) U/L, total bilirubin 55.5 (34.5-75.3) umol/L, with DAT specificity for IgG, C3d, or both in 34.1%, 2.3%, and 61.4% of patients, respectively. There was one case of IgA AIHA (2.3%)

Twenty-four patients had secondary wAIHA (53.3%), most commonly due to lymphoproliferative disorders (LPD, 62.5%) followed by Evan's syndrome (20.8%), and autoimmune conditions (16.6%), including two patients (8.3%) who developed non-Hodgkin's lymphoma after diagnosis of wAIHA. Bone marrow evaluation was performed in 21 (45.7%) of cases, which diagnosed an underlying LPD in two cases (9.5%), and one case each of myelofibrosis and myelodysplastic neoplasm.

The median follow-up was 33.9 (4.8-52) months. Hospitalisation was required for 26 (56.5%) of cases, with a median length of 7 (5-11.8) days. Corticosteroids (most commonly prednisolone) was commenced as first-line therapy in 42 (91.3%) patients, which was first tapered in 26 (17-34) days (n=29) and ceased 137.5 (80.3-293.8) days (n=22) later. Where assessable (n=34), the overall response rate (ORR) was 88.2%, most commonly response (Hb improvement by ≥ 20 g/L from baseline: 55.1%), complete response (Hb within 10 g/L of historical values, or normal range with normal haemolytic markers: 14.7%), and complete remission (complete response and off treatment for ≥ 4 weeks: 29.4%). Rituximab monotherapy (off-label) was given at first and second-line in four and seven patients (36.4 and 63.6%), respectively. The ORR was 81.8%, most commonly response (36.4%), followed by complete response (27.3%), and complete remission (18.2%).

Venous thromboembolism and infections complicated six (13%) and thirteen (28.3%) patients. Mortality occurred in fourteen (30.4%) patients, including six (42.9%) which occurred within two weeks of diagnosis. These included five patients due to acute haemolytic crisis, and one due to sepsis. The mortality rate was comparable between the primary and secondary wAIHA cohorts (31.8% vs 29.2%). The mortality rate was higher in patients who did not receive rituximab, compared to those who did (37.1 vs 9.1%, Fisher's exact P=0.13).

Limitations of the audit include the small sample size, the possible loss of some cases that were diagnosed by private pathology providers without treatment in the public hospital system, and the impact of the COVID-19 pandemic during the study period.

Conclusion: To our knowledge, this report is the first comprehensive attempt to describe the contemporary incidence, real-world treatments, and outcomes of wAIHA in an Australian cohort, which noted significant healthcare burden including hospitalisation, corticosteroid use, mortality and morbidity rates.

However, further studies are needed to explore the emergence of immunotherapy associated haemolytic complications, the future impact of expanding treatment options in immune haematology, and the unexpectedly high mortality rate we observed in wAIHA also consistently reported in other publications.

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2025
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