JHSM
Journal of Health Sciences and Medicine

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Original Article
Clinical association of anemia subtypes with gallstone disease: evidence from a rural cohort study
Abstract
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 ?² 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.

Keywords : Gallstones, anemia, macrocytic anemia, hemolysis, ineffective erythropoiesis, risk factors

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1. Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep. 2005;7 (2):132-140. doi:10.1007/s11894-005-0051-8
2. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012;6(2):172-187. doi:10.5009/gnl. 2012.6.2.172
3. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999;117(3):632-639. doi:10.1016/s0016-5085(99)70456-7
4. Karayalcin R, Genc V, Karaca AS, Ozaksit G. Prevalence of cholelithiasis in a Turkish population sample of postmenopausal women. Turk J Gastroenterol. 2010;21(4):416-420.
5. Trotman BW, Soloway RD. Pigment gallstone disease: summary of the National Institutes of Health--international workshop. Hepatology. 1982;2(6):879-884. doi:10.1002/hep.1840020624
6. Vitek L, Carey MC. Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life. Eur J Clin Invest. 2003;33(9):799-810. doi:10.1046/j.1365-2362.2003.01214.x
7. Aydogdu I, Sari R, Ulu R, Sevinc A. The frequency of gallbladder stones in patients with pernicious anemia. J Surg Res. 2001;101(2):120-123. doi: 10.1006/jsre.2001.6269
8. Pamuk GE, Umit H, Harmandar F, Yesil N. Patients with iron deficiency anemia have an increased prevalence of gallstones. Ann Hematol. 2009; 88(1):17-20. doi: 10.1007/s00277-008-0557-x
9. Cikim G, Hatipoglu HS, Susam S. Evaluation of homocysteine, vitamin, and trace element levels in women with gallstones. J Trace Elem Med Biol. 2023;78:127177. doi:10.1016/j.jtemb.2023.127177
10. Chen P, Yang C, Ding J, Li Y, Hu W, Zhang Q. Association of dietary vitamin intake with gallstone risk in US adults: a cross-sectional NHANES study. Eur J Med Res. 2025;30(1):535. doi:10.1186/s40001-025-02841-8
11. Liu CM, Hsu CT, Li CY, Chen CC, Liu ML, Liu JH. A population-based cohort study of symptomatic gallstone disease in diabetic patients. World J Gastroenterol. 2012;18(14):1652-1659. doi:10.3748/wjg.v18.i14.1652
12. Liu CM, Tung TH, Chou P, et al. Clinical correlation of gallstone disease in a Chinese population in Taiwan: experience at Cheng Hsin General Hospital. World J Gastroenterol. 2006;12(8):1281-1286. doi:10.3748/wjg.v12.i8.1281
13. Loria P, Lonardo A, Lombardini S, et al. Gallstone disease in non-alcoholic fatty liver: prevalence and associated factors. J Gastroenterol Hepatol. 2005;20(8):1176-1184. doi:10.1111/j.1440-1746.2005.03924.x
14. Mendez-Sanchez N, Chavez-Tapia NC, Motola-Kuba D, et al. Metabolic syndrome as a risk factor for gallstone disease. World J Gastroenterol. 2005;11(11):1653-1657. doi:10.3748/wjg.v11.i11.1653
15. Zhuo H, Fan J, Zhang B, et al. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure. Open Med (Wars). 2022;17(1):1455-1465. doi:10.1515/med-2022-0549
16. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747-1750. doi:10.1182/blood-2005-07-3046
17. Adeniyi OF, Akinsete AM, Odeghe EA, et al. Cholelithiasis in children and adolescents with sickle cell disease: experience in a resource-limited setting. Ann Afr Med. 2022;21(1):58-64. doi:10.4103/aam.aam_81_20
18. Aguado A, Moratalla-Navarro F, Lopez-Simarro F, Moreno V. MorbiNet: multimorbidity networks in adult general population. Analysis of type 2 diabetes mellitus comorbidity. Sci Rep. 2020;10(1):2416. doi:10.1038/s41598-020-59336-1
19. Alkindi S, Almufargi SS, Pathare A. Clinical and laboratory parameters, risk factors predisposing to the development of priapism in sickle cell patients. Exp Biol Med (Maywood). 2020;245(1):79-83. doi:10.1177/15353 70219892846
20. Al Talhi Y, Shirah BH, Altowairqi M, Yousef Y. Laparoscopic cholecystectomy for cholelithiasis in children with sickle cell disease. Clin J Gastroenterol. 2017;10(4):320-326. doi:10.1007/s12328-017-0750-3
21. Cuciureanu T, Singeap AM, Chiriac S, Girleanu I, Trifan A, Stanciu C. An unusual case of cholecystoduodenal fistula in a nonagenarian patient. Medical-Surgical Journal-Revista Medico-Chirurgicala. 2017; 121(2):360-365.
22. Mohammed S, Addae S, Suleiman S, et al. Serum calcium, parathyroid hormone, and vitamin D status in children and young adults with sickle cell disease. Ann Clin Biochem. 1993;30(1):45-51. doi:10.1177/0004563293 03000108
23. Ariandi I, Saleh S, Benyamin AF, Harjianti T, Minhajat R, Bayu D. ß-thalassemia intermedia with autoimmune hemolytic anemia and multiple cholelithiasis complications. Gazzetta Medica Italiana Archivio per le Scienze Mediche. 2023;182(4):240-243. doi:10.23736/s03 93-3660.22.04881-1
24. Gardner K, Suddle A, Kane P, et al. How we treat sickle hepatopathy and liver transplantation in adults. Blood. 2014;123(15):2302-2307. doi:10. 1182/blood-2013-12-542076
25. AlSaleh N, Alaa Adeen AM, Hetta OE, et al. Emergency cholecystectomy: risk factors and impact of delay on electively booked patients, a 5-year experience of a tertiary care center. BMC Surg. 2024;24(1):396. doi:10.1186/s12893-024-02694-8
26. Rege RV. Biliary stones. Current Opinion in Gastroenterology. 1992;8(5): 749-755. doi:10.1097/00001574-199210000-00004
27. Rosenbaum H, Sidransky E. Cholelithiasis in patients with Gaucher disease. Blood Cells Mol Dis. 2002;28(1):21-27. doi:10.1006/bcmd.2001.0480
28. Lotfi M, Keramati P, Assdsangabi R, Nabavizadeh SA, Karimi M. Ultrasonographic assessment of the prevalence of cholelithiasis and biliary sludge in beta-thalassemia patients in Iran. Med Sci Monit. 2009;15(8):CR398-402.
29. Siregar DR, Muhar AM, Pohan DP. The role of cholelithiasis risk factors in stone types in cholelithiasis patients at Universitas Sumatera Utara Hospital. Bali Medical Journal. 2021;10(1):63-65. doi:10.15562/bmj.v10 i1.2139
Article available in :
Volume 9, Issue 1, 2026
Page : 126-132
https://doi.org/10.32322/jhsm.1805444
Article Information
Received : 17 Eki 2025
Accepted : 08 Ara 2025
Published : 05 Oca 2026
Corresponding Author :

Mehmet Berksun Tutan: Department of General Surgery, Hitit University Erol Olçok Training and Research Hospital, Çorum, Turkiye

[email protected]
Citation : Tutan MB, Tutan D, Koyun ON. Clinical association of anemia subtypes with gallstone disease: evidence from a rural cohort study. J Health Sci Med. 2026;9(1):126-132. doi:10.32322/jhsm.1805444

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