Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia-A Systematic Review and Meta-Analysis

Abstract

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA.

Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study.

Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively.

Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.

Keywords: autoantibodies; autoimmune haemolytic anaemia; epidemiology; meta-analysis; review; secondary causes.

Figure 1

PRISMA flowchart. Studies identified through PubMed 14 July 2020. Studies were first reviewed based on title and abstract, which excluded 2459 studies. 176 studies were eligible for full-text review, and 149 studies were then excluded, mostly due to wrong patient population. 27 studies were included in this systematic review for data extraction and meta-analysis.

Figure 2

Meta-analysis of the proportion of females in patients with warm autoimmune haemolytic anaemia (wAIHA) with 95% CI and the weight of the included studies. Meta-analysis of the proportion of females with wAIHA by age-group in the studies, generation using the meta-prop procedure in Stata. I² = 0.0% represents a presumably very low heterogeneity in the included studies, as the 95% CI are overlapping. Each of the black $■$-symbols represents the ES and 95% CI for one study. The orange ◊-symbols are the pool effect estimates from subgroups and overall.

Figure 3

Meta-analysis of proportion of secondary warm autoimmune haemolytic anaemia (wAIHA) with 95% CI and the weight of the included studies. Meta-analysis of the proportion of patients with secondary wAIHA by level of location of wAIHA-diagnosis, generation using the meta-prop procedure in Stata. As shown, more patients are diagnosed with primary wAIHA in primary centres, compared with referral centres. I² = 0.0% represents a presumably very low heterogeneity in the included studies, as the 95% CIs are overlapping. Each of the black $■$-symbols represents the ES and 95% CI for one study. The orange ◊-symbols are the pool effect estimates from subgroups and overall.