The Relationship between Immunological and Biological Markers in Thalassemia Patients after Blood Transfusion
DOI:
https://doi.org/10.33003/fjs-2026-1022-6036Keywords:
Thalassemia, Blood Transfusion, Cytokines, Iron Overload, Inflammatory BiomarkersAbstract
Thalassemia patients require repeated blood transfusions, which may alter immunological and biological markers, potentially influencing inflammation, immune function, and complications. This study aimed to evaluate immunological and biological markers in transfused thalassemia patients and determine their associations with transfusion-related clinical and laboratory alterations. An analytical case–control study included 80 transfusion-dependent β-thalassemia patients and 40 healthy controls from January 2025 to April 2026. Clinical, transfusion, chelation, and anthropometric data were recorded. Blood samples were collected before scheduled transfusion. Complete blood count, ferritin, AST, ALT, and hs-CRP were measured using standardized laboratory methods, while serum IL-6, TNF-α, and IL-10 were quantified by ELISA. Cardiac function and growth parameters were assessed. Ethical approval and informed consent were obtained from all participants. The study included 80 thalassemia patients and 40 healthy controls. Patients demonstrated significantly higher CRP, IL-6, TNF-α, IL-10, ferritin, AST, and ALT levels, alongside significantly lower hemoglobin and left ventricular ejection fraction (all P<0.001). Patients received 3.5 ± 1.0 transfusions monthly, and 65.0% received iron-chelation therapy. Normal growth was observed in 85.0% of patients versus 95.0% of controls. Overall health status was significantly poorer among thalassemia patients compared with healthy controls (P<0.001). Transfusion-dependent thalassemia was associated with marked inflammatory, immunological, hematological, and biochemical alterations, particularly elevated cytokines, ferritin, and liver enzymes. These findings support integrated biomarker monitoring to identify transfusion-related complications, assess iron overload, and improve long-term clinical management of affected patients.
References
Ababneh, S., Abu Siyam, A. A., Alzoubi, M. M., Al-Sawalha, N. A., Al Sukhni, F. F., Al Rahbeni, T., Al-Mugheed, K., & Abdelaliem, S. M. F. (2025). Assessment of health-related quality of life in transfusion-dependent beta-thalassemia. Scientific Reports, 15, 32267. https://doi.org/10.1038/s41598-025-07728-6
Abd El-Hamid, M. E. S., Younis, Y. A. H. S., Mansour, M. M., Dawoud, A. M., El Derbaly, S. A., & Mansour, M. M. (2026). Assessment of CTLA-4, LAG-3, and TIM-3 expression in pediatric patients with β-thalassemia major and their association with alloimmunization. Journal of Pediatric Hematology/Oncology.
Al-Hakeim, H. K., et al. (2025). In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms. Journal of Affective Disorders.
Almorish, M. A. W., Al-Absi, B., Elkhalifa, A. M. E., Alhamidi, A. H., et al. (2024). Red blood cell alloimmunization in blood transfusion-dependent β-thalassemia major patients in Sana’a City, Yemen. Scientific Reports, 14, 1005. https://doi.org/10.1038/s41598-024-51561-2
Alshihmani, I., Faraj, S. A., Oodi, A., Eftekhar, Z., Jalali Far, M. A., & Pourfathollah, A. A. (2025). Low rate of red cell alloimmunization among multiply transfused beta-thalassemia major patients in the Wasit Province of Iraq. Transfusion and Apheresis Science, 64(6), 104267. https://doi.org/10.1016/j.transci.2025.104267
Aneed, N. S., Fadhil, R. K., Kadhum, S. M., Sadoon, N. M., Hussein, B. J., & Abood, A. J. (2024). Immunological assessment of interleukin-6 and 8 in Baghdad patients with β-thalassemia. South Eastern European Journal of Public Health, 187–194. https://doi.org/10.70135/seejph.vi.1659
Aydinok, Y., et al. (2022). Current approaches to the assessment and management of iron overload in transfusion-dependent thalassemia. Blood Reviews, 56, 100982.
De Sanctis, V., Soliman, A. T., & Skordis, N. (2023). Growth and endocrine complications in transfusion-dependent thalassemia. Acta Biomedica, 94, e2023124.
Drahos, J., Boateng-Kuffour, A., Calvert, M., Levine, L., Dongha, N., Li, N., Pakbaz, Z., Shah, F., & Martin, A. P. (2024). Health-related quality-of-life impacts associated with transfusion-dependent β-thalassemia in the USA and UK: A qualitative assessment. The Patient, 17(4), 421–439. https://doi.org/10.1007/s40271-024-00678-7
Dudley, J., et al. (2024). Health-related quality of life with standard and curative therapies in thalassemia: A narrative literature review. Annals of the New York Academy of Sciences, 1533, 32–48. https://doi.org/10.1111/nyas.15100
Dutta, A., et al. (2023). Alloantibody among thalassemia patients receiving multiple blood transfusions at a tertiary care hospital in India. Bioinformation, 19, 937–943.
El-Rasheidy, F. H., et al. (2022). Inflammatory and immunological alterations in patients with transfusion-dependent β-thalassemia. Egyptian Journal of Immunology, 29, 45–56.
Fadhil, N. A. (2026). Serum immune-regulatory biomarkers in beta-thalassemia: A case-control study of soluble human leukocyte antigen-G, CD4, CD8, and interleukin-17A. Jurnal Widya Medika, 12(3). https://doi.org/10.33508/jwm.v12i3.8943
Fadhil, N. A., et al. (2026). Th1/Th2 cytokine imbalance with novel IL-17F elevation in Iraqi transfusion-dependent beta-thalassemia: A dual-platform diagnostic study. Cytokine.
Farmakis, D., Porter, J., Taher, A., Cappellini, M. D., Angastiniotis, M., & Eleftheriou, A. (2022). 2021 Thalassaemia International Federation guidelines for the management of transfusion-dependent thalassemia. HemaSphere, 6(8), e732. https://doi.org/10.1097/HS9.0000000000000732
Garozzo, G., Messina, R., Manca, P., & Aquilina, A. (2024). Transfusion in hemoglobinopathies and red blood cell alloimmunization: Data from Sicily, Sardinia, and Malta. Blood Transfusion, 22(2), 111–121. https://doi.org/10.2450/BloodTransfus.465
Genç, B., et al. (2024). Evaluation of microstructural changes in the brain in transfusion-dependent thalassemia patients with advanced magnetic resonance imaging techniques. Neuroradiology, 66(10), 1721–1728. https://doi.org/10.1007/s00234-024-03414-y
Indriani, V., Mulyono, B., Triyono, T., Handayaningsih, A. E., & Chandra, L. A. (2025). Prevalence of alloimmunization events in thalassemia patients with repeated transfusions in the Rhesus blood group system: A systematic review and meta-analysis. Journal of Clinical Medicine Research, 17(2), 106–118. https://doi.org/10.14740/jocmr6142
Kargar, M., Kaydani, G. A., Keikhaei, B., Saki, N., & Jalali Far, M. A. (2025). Association between HLA-DRB104, HLA-DQB103, and HLA-DQB1*06 with alloimmunization in transfusion-dependent patients with thalassemia: The first case-control study in Iran. Annals of Hematology, 104. https://doi.org/10.1007/s00277-025-06288-z
Kurban, L. A., et al. (2023). Optimized serum ferritin prediction of iron overload in transfusion-dependent thalassemia: Likelihood ratio and age-adjustment approach. Annals of Saudi Medicine, 43(2), 90–99. https://doi.org/10.5144/0256-4947.2023.90
Kuriri, F. A., et al. (2023). Red blood cell alloimmunization and autoimmunization in blood transfusion-dependent sickle cell disease and β-thalassemia patients in Al-Ahsa Region, Saudi Arabia. Journal of Blood Medicine, 14, 263–272. https://doi.org/10.1155/2023/3239960
Meloni, A., et al. (2026). Determinants of liver stiffness assessed by transient elastography in transfusion-dependent thalassemia. Expert Review of Hematology.
Meloni, A., Pistoia, L., Spasiano, A., Cossu, A., Casini, T., Massa, A., Bagnato, S., Putti, M. C., Maffei, S., Positano, V., Pepe, A., Cademartiri, F., & Vassalle, C. (2024). Oxidative stress and antioxidant status in adult patients with transfusion-dependent thalassemia: Correlation with demographic, laboratory, and clinical biomarkers. Antioxidants, 13(4), 446. https://doi.org/10.3390/antiox13040446
Mohammed, A. J., & Yenzeel, J. H. (2024). Assessment of interleukin-1β, interleukin-6, and some biochemical parameters in a sample of Iraqi patients with β-thalassemia major. Ibn Al-Haitham Journal for Pure and Applied Sciences, 37(4). https://doi.org/10.30526/37.4.3457
Musallam, K. M., Bou-Fakhredin, R., Cappellini, M. D., & Taher, A. T. (2023). Clinical burden and management considerations in transfusion-dependent β-thalassemia. Blood Reviews, 58, 101013.
Özköteş, N. Ö., Karapınar, T. H., Okur Acar, S., Ayhan, Y., Gülez, N., Oymak, Y., & Genel, F. (2025). Evaluation of immune functions in transfusion-dependent thalassemia patients with alloimmunization. Turkish Journal of Hematology, 42(4), 306–314. https://doi.org/10.4274/tjh.galenos.2025.2025.0106
Pappa, E., et al. (2024). Quality of life in transfusion-dependent thalassemia patients in Greece before and during the COVID-19 pandemic. Journal of Patient-Reported Outcomes, 8, 45.
Pepe, A., et al. (2022). Magnetic resonance assessment of cardiac and hepatic iron in transfusion-dependent thalassemia. Journal of Clinical Medicine, 11, 5297.
Permana, D. A., Susanah, S., Adrizain, R., Rahayuningsih, S. E., Dhamayanti, M., & Rakhmilla, L. E. (2024). Factors related to the quality of life in children with transfusion-dependent thalassemia. Pediatric Hematology and Oncology, 41(3), 179–197. https://doi.org/10.1080/08880018.2023.2286962
Purnamasari, I., Rahayu, C. D., Susanto, T., Peperawati, P. R., & Supriyati, A. (2025). Factors affecting the quality of life of children with transfusion-dependent thalassemia: A cross-sectional study. Acta Medica Academica, 54(2), 100–111. https://doi.org/10.5644/ama2006-124.486
Rabie, M. A. F., El Benhawy, S. A., Masoud, I. M., et al. (2024). Impact of met-haemoglobin and oxidative stress on endothelial function in patients with transfusion-dependent β-thalassemia. Scientific Reports, 14, 25328. https://doi.org/10.1038/s41598-024-74930-3
Ridha, M. A. S., Kahlol, M. K., & Al-Hakeim, H. K. (2024). Alterations in trace elements and cation profiles in transfusion-dependent thalassemia patients. Transfusion and Apheresis Science, 63(4), 103954. https://doi.org/10.1016/j.transci.2024.103954
Settakorn, K., Hantrakool, S., Petiwathayakorn, T., Hutachok, N., Tantiworawit, A., Charoenkwan, P., Chalortham, N., Chompupoung, A., Paradee, N., Koonyosying, P., & Srichairatanakool, S. (2024). A randomized placebo-controlled clinical trial of oral green tea epigallocatechin-3-gallate on erythropoiesis and oxidative stress in transfusion-dependent β-thalassemia patients. Frontiers in Molecular Biosciences, 10, 1248742. https://doi.org/10.3389/fmolb.2023.1248742
Shah, F. T., et al. (2023). Long-term clinical outcomes and organ complications in regularly transfused patients with β-thalassemia. British Journal of Haematology, 202, 647–660
Tantiworawit, A., et al. (2025). Dysregulation of ceruloplasmin, α2-macroglobulin, and alpha-2-HS-glycoprotein in transfusion-dependent thalassemia. International Journal of Molecular Sciences.
Teawtrakul, N., Songdej, D., Hantaweepant, C., Tantiworawit, A., Lauhasurayotin, S., Torcharus, K., et al. (2022). Red blood cell alloimmunization and other transfusion-related complications in patients with transfusion-dependent thalassemia: A multicenter study in Thailand. Transfusion, 62(10), 2039–2047. https://doi.org/10.1111/trf.17068
Watany, M. M., & Elhosary, M. M. (2024). Clinical utility of circulating TWEAK and CD163 as biomarkers of iron-induced cardiac decompensation in transfusion-dependent thalassemia major. Cytokine, 173, 156443. https://doi.org/10.1016/j.cyto.2023.156443
Yalcin, N., Sadri, S., Ertınmaz Özkan, A., Gürsoy, V., & Koca, N. (2024). Elevated plasma atherogenic and triglyceride-glucose indices: Markers of cardiovascular risk in transfusion-dependent thalassemia. Hemoglobin, 48(4), 292–300. https://doi.org/10.1080/03630269.2024.2412111
Yang, K., et al. (2024). Effects of thalidomide on erythropoiesis and iron homeostasis in transfusion-dependent β-thalassemia. Mediterranean Journal of Hematology and Infectious Diseases, 16.
Zhang, X., Li, Y., Yan, B., Li, X., Sun, A., & Gui, S. (2023). Red blood cell alloimmunization in thalassemia patients with regular transfusion in China: A systematic review and meta-analysis. Transfusion Clinique et Biologique, 30(2), 256–262. https://doi.org/10.1016/j.tracli.2023.02.001
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