Clinical association of anemia subtypes with gallstone disease: evidence from a rural cohort study

Aims: Gallstone disease is common worldwide, and while hemolytic anemias are well-established risk factors for pigment stone formation, the relationship between other anemia subtypes and gallstone prevalence in the general adult population remains insufficiently characterized. This study aims to evaluate the association between anemia subtypes and gallstone disease in a large unselected cohort of adults presenting with dyspeptic symptoms. Methods: We conducted a retrospective observational study including adult patients who underwent both abdominal ultrasonography and laboratory testing between January 2020 and July 2025. Demographic, hematologic, and biochemical parameters were collected. Anemia was defined by standard hemoglobin thresholds and classified into microcytic, normocytic, and macrocytic subtypes by mean corpuscular volume. Comparisons between groups were performed using χ² and non parametric tests. Logistic regression and ROC analysis assessed the predictive value of hemoglobin for gallstone detection. Results: A total of 1.660 patients were analyzed, of whom 311 (18.7%) had gallstones. Anemia was present in 21.9% of the cohort and was more frequent in patients with gallstones compared to those without (27.0% vs. 20.8%, p=0.016). Among anemic patients, macrocytic anemia showed a markedly higher prevalence of gallstones (70%) compared to microcytic (19.6%) and normocytic (23.2%) anemia (p=0.001). Patients with gallstones also had lower hemoglobin (13.2 vs. 13.4 g/dl, p=0.012), reduced serum iron, higher RDW, and elevated ALP and GGT, with lower albumin levels. Logistic regression confirmed an independent inverse association between hemoglobin and gallstones (OR=0.90, 95% CI: 0.84-0.97, p=0.003). However, hemoglobin had limited discriminatory power (AUC 0.572 in men, 0.533 in women). Conclusion: In this large rural cohort, anemia-particularly macrocytic anemia-was significantly associated with gallstone disease, extending the link between hematologic disorders and biliary pathology beyond classic hemolytic conditions. Recognition of anemia subtypes in patients with biliary symptoms may improve risk stratification and guide metabolic and nutritional assessment. Prospective multicenter studies with detailed hematologic profiling and stone composition analysis are warranted to further clarify underlying mechanisms.