Acquired hemolytic anemia, or AHA, is not a single disease but a heterogeneous collection of conditions in which red blood cells are destroyed prematurely by mechanisms outside the cells themselves. Because the body cannot replace the lost cells quickly enough, patients are left with too few oxygen-carrying red cells, producing dizziness, weakness, irregular heartbeat, and shortness of breath. In severe cases, free hemoglobin spilled into the bloodstream can trigger kidney injury, stroke, or heart attack, and the disorder’s causes range from autoimmune attack and transfusion reactions to medications, infections, and metal poisoning. The most common subtype worldwide, autoimmune hemolytic anemia, strikes roughly one to three people per 100,000 each year, while paroxysmal nocturnal hemoglobinuria affects only about 15.9 individuals per million.

Standard treatment depends on the underlying cause and includes corticosteroids, B-cell-depleting monoclonal antibodies, blood transfusion, splenectomy, or hematopoietic stem cell transplantation. Yet even with these options, patients remain vulnerable to serious complications, including cardiovascular disease, immune dysfunction, infection, thrombotic events, and pulmonary hypertension. That persistent burden of illness is precisely why the Taiwanese research team, led by investigators affiliated with China Medical University, set out to ask whether Chinese herbal medicine, which is reimbursed and systematically recorded under Taiwan’s National Health Insurance program, might be associated with better long-term outcomes in this population.

The team mined claims data from 2008 to 2019, identifying patients newly diagnosed with acquired hemolytic anemia between 2010 and 2017 using standard diagnostic codes. To ensure diagnoses were reliable, they required at least three outpatient claims or one inpatient claim for the condition. After excluding patients missing demographic information, those who underwent splenectomy, and those whose herbal prescriptions fell below a prespecified cumulative threshold of 14 days in the year following diagnosis, the cohort comprised 6,807 eligible patients, of whom 909 were classified as herbal medicine users and 2,229 as non-users.

Because patients who seek out traditional medicine often differ systematically from those who do not, the researchers used propensity score matching to build comparable groups. Matching on age, sex, Charlson comorbidity index, blood transfusion history, and iron chelation therapy yielded 790 well-balanced pairs. Before matching, herbal users were younger, more likely to be female, and carried a lower comorbidity burden than non-users, differences that the matching procedure largely erased and that the subsequent statistical models further adjusted for.

The survival signal was striking. In a fully adjusted Cox proportional hazards model, herbal medicine users had a 37 percent lower risk of death from any cause than matched non-users, with an adjusted hazard ratio of 0.63 and a 95 percent confidence interval of 0.51 to 0.77. Kaplan-Meier curves confirmed better survival among users, with a log-rank p-value of 0.0006. The benefit extended to the cardiovascular realm: after multivariable adjustment, herbal treatment was associated with a 62 percent reduction in cardiovascular disease-related mortality, corresponding to an adjusted hazard ratio of 0.38. Older age, heavier comorbidity burden, and blood transfusion each independently raised mortality risk, while female sex was linked to lower all-cause mortality. Sensitivity analyses using different cumulative exposure cutoffs produced consistent results.

Beyond the survival analysis, the study broke new ground by mapping how physicians actually combine herbal products in this patient group. Using association rule mining and network visualization, the team analyzed more than 27,000 prescriptions and identified two distinct clusters. The first, a hematologic-supportive cluster, centered on Dang-Gui, Huang-Qi, Gui-Pi-Tang, E-Jiao, and Dan-Shen, with the Dang-Gui to Huang-Qi pair showing the strongest co-prescription relationship. The second cluster paired Jie-Geng with Bei-Mu. Gui-Pi-Tang was the most frequently prescribed formula overall, while Huang-Qi, Dan-Shen, Bei-Mu, Jie-Geng, Dang-Gui, and E-Jiao led among single herbs.

Experimental literature offers plausible biological explanations for why these particular herbs cluster together. Polysaccharides from Angelica sinensis, the botanical source of Dang-Gui, appear to protect hematopoietic cells from oxidative injury and reverse anemia of chronic disease in animal models. Huang-Qi, derived from Astragalus species, has been shown to raise red cell, white cell, hemoglobin, and hematocrit levels in anemic animals, and its principal constituent astragaloside IV has demonstrated anti-anemic effects in chemotherapy-induced models as well as potential benefits in heart failure. Dan-Shen, the root of Salvia miltiorrhiza, reduces erythrocyte membrane damage and improves blood viscosity, while collagen-derived peptides from E-Jiao stimulate hematopoiesis. Jie-Geng, meanwhile, has shown cardioprotective effects by blocking angiotensin II-induced cardiomyocyte apoptosis. These mechanisms align neatly with the observed reduction in both overall and cardiovascular mortality.

The findings echo earlier Taiwanese studies in related blood disorders. Prior work found that herbal medicine use was associated with improved survival in aplastic anemia and with reduced all-cause, diabetes-related, and cardiovascular mortality in hereditary hemolytic anemias, with overlapping prescription patterns featuring Dang-Gui, Huang-Qi, and Dan-Shen. The consistency across these independent cohorts strengthens the case that the current results are not a statistical fluke, though it also means the new study inherits some of the same methodological constraints.

Those constraints matter. Claims data contain no laboratory values or physical assessments, leaving room for residual confounding and possible misclassification of exposure or outcome. The excluded patients differed from the included ones in sex, age, comorbidity, and transfusion use, raising the possibility of selection bias. Individualized dosing information was unavailable, and the matching design precluded dose-response analysis. The authors also note that multi-herb combinations common in traditional practice may interact with pharmaceuticals in ways the study could not capture, and that healthcare systems elsewhere may differ from Taiwan’s. Still, the researchers argue that the identified herbal clusters provide a concrete, testable roadmap for prospective cohort studies and mechanistic experiments aimed at determining whether these centuries-old formulations can genuinely extend survival for patients with acquired hemolytic anemia.

Subject of Research: Association between Chinese herbal medicine use and mortality in acquired hemolytic anemia

Article Title: Chinese herbal medicine therapy reduces all-cause and cardiovascular disease-related mortalities in acquired hemolytic anemia: A Taiwanese nationwide retrospective cohort study

Article References: Chou, C.-H., Chiou, J.-S., Hsu, Y.-L., Chiu, M.-L., Chen, C.-J., Liang, W.-M., Tsai, F.-J., Wu, Y.-C., Chou, I.-C., Lin, T.-H., Liao, C.-C., Huang, S.-M., Lin, C.-W., Li, T.-M., Li, J.-P., & Lin, Y.-J. (2026). Chinese herbal medicine therapy reduces all-cause and cardiovascular disease-related mortalities in acquired hemolytic anemia: A Taiwanese nationwide retrospective cohort study. Heliyon, 12(15), Article e45157. https://doi.org/10.1016/j.heliyon.2026.e45157

Image Credits: AI Generated

DOI: 10.1016/j.heliyon.2026.e45157

Keywords: acquired hemolytic anemia, Chinese herbal medicine, cardiovascular mortality, all-cause mortality, Taiwan National Health Insurance, propensity score matching, Cox proportional hazards, Dang-Gui, Huang-Qi, autoimmune hemolytic anemia, prescription pattern analysis, traditional Chinese medicine