Additional population-based studies of autoimmune hemolytic anemia and its management are needed to reduce mortality in this patient population.
Autoimmune hemolytic anemia (AIHA) is typically a chronic condition with a good prognosis overall, but research on prognosis and causes of death in population-based longitudinal cohorts is scarce. A study of patients with AIHA in Denmark aimed to provide clarity on survival rates and causes of death in these patients vs the general population.
AIHA is heterogenous and involves cold-type, warm-type, or mixed-type autoantibodies that target red blood cells and cause hemolysis. The various types of AIHA present in different clinical phenotypes. Warm-type AIHA can be primary or caused by underlying disease such as lupus erythematosus or lymphoproliferative disorders, while cold-type’s main phenotype is cold agglutinin disease (CAD), which is driven by clonal lymphoproliferative cells in bone marrow.
In general, AIHA is associated with morbidity in patients—including thromboses, cancers, and connective tissue diseases—as well as mortality. Recent research, however, suggests that survival rates may be lower in patients with AIHA than previously thought. One French study, in particular, reported a 1-year survival rate of 79.5% in a cohort of nearly 10,000 patients. This contradicts previous reports of survival rates between 79% and 96%. Patients with secondary AIHA faced more dismal 1-year survival rates, as low as 52%. Causes of death have not been widely reported and have not been compared with the general public.
The current study included 2650 patients with AIHA or CAD between 1980 and 2016 and 130,801 matched comparators in the general population. A total of 1460 patients had primary AIHA, 1078 had secondary AIHA, and 112 had CAD. The groups had 72,124 comparators; 53,511 comparators; and 5166 comparators, respectively. Overall survival and cause-specific mortality from anemia, infection, cardiovascular disease, cancers, bleeding, and other causes were reported in cumulative incidence proportions.
Median survival was 9.8 years in primary AIHA, 3.3 years for secondary AIHA, and 8.8 years for CAD. One-year survival rates were 82.7%, 69.1%, and 85.5%, respectively. Women and younger patients typically tended to have better survival. Over the course of the study period, overall and median survival improved. Patients younger than 30 years at diagnosis had a prognosis comparable to the general population, but all other age groups with AIHA had worse survival.
At 1-year post diagnosis, cumulative cause-specific mortality in patients with AIHA was higher than in the general population. Adjusted cause-specific HRs in primary AIHA were 10.1 for death attributed to hematological cancers and 9.3 for death attributed to infections. In secondary AIHA, the cause-specific HR for death by infections was 5.9. The adjusted HR for bleeding-related death was 9.0 in primary AIHA and 8.1 in secondary AIHA. Cardiovascular death, infections, and hematological cancers remained common causes of death after 5 years in patients with AIHA.
Overall, the 3 types of AIHA showed increased overall and cause-specific mortality compared with the general population in this study, even after adjusting for comorbidities.
“For all subtypes, the first year after diagnosis of AIHA was associated with the highest mortality,” the authors wrote. “Leading causes of death in primary AIHA were cardiovascular disease, anemia, and infections. For secondary AIHA patients, solid cancer, hematological cancer, and cardiovascular diseases were the most commonly registered causes of death.”
While median survival improved over the course of the study, suggesting management of AIHA has improved over time, secondary AIHA did not see the same change in prognosis, and the overall prognosis for AIHA remains poor. The results suggest that patients with AIHA and CAD are a population with unmet management needs that warrant further research.
Hansen DL, Möller S, Frederiksen H. Survival in autoimmune hemolytic anemia remains poor, results from a nationwide cohort with 37 years of follow-up. Eur J Haematol. Published online March 11, 2022. doi:10.1111/ejh.13764