Disease-Associated Anemia: An Integrated Review of Pathophysiology, Diagnosis, and Therapeutic Implications

Authors

  • Nanny Djaya Atma Jaya Catholic University, Jakarta Indonesia Author
  • Irene Vanessa Atma Jaya Catholic University, Jakarta Indonesia Author
  • Christina Jeanny Atma Jaya Catholic University, Jakarta Indonesia Author

DOI:

https://doi.org/10.30872/jtpc.v9i2.310

Keywords:

anemia, chronic disease, haemoglobinopathy, iron metabolism, bone marrow failure

Abstract

Disease-associated anemia is a heterogeneous and prevalent clinical problem, arising from diverse underlying conditions that interfere with erythropoiesis, red blood cell survival, iron metabolism, or blood loss. Major underlying causes include chronic kidney disease, chronic inflammation or infection, malignancy, bone marrow failure syndromes, haemoglobinopathies, autoimmune haemolysis, and chronic blood loss (e.g., gastrointestinal bleeding or parasitic infection). Distinct pathophysiological mechanisms impaired erythrocyte production, increased erythrocyte destruction, and iron sequestration or chronic blood loss often overlap, complicating diagnosis and treatment. Recent advances in understanding molecular regulators such as hepcidin and erythroferrone, and therapeutic innovations including hypoxia-inducible-factor (HIF) stabilizers, hepcidin antagonists, gene therapy for haemoglobinopathies, and refined iron-management protocols, promise improved outcomes. This review synthesizes current evidence on mechanisms, diagnostic approaches, and management strategies across major disease categories causing anemia.

Downloads

Download data is not yet available.

References

1. Agarwal, A. K., Kalra, P. A., Kothari, J., Kher, V., & Kalantar-Zadeh, K. (2021). Iron metabolism and management in chronic kidney disease. Kidney International Supplements, 11(1), 56–64. https://doi.org/10.1016/j.kisu.2020.12.003

2. Al-Naseem, A., Sallam, A., Choudhury, S., & Thachil, J. (2021). Iron deficiency without anaemia: A diagnosis that matters. Clinical Medicine, 21(2), 107–113. https://doi.org/10.7861/clinmed.2020-0582

3. Atkinson, J., Safiri, S., & GBD 2021 Anaemia Collaborators. (2025). Getting back on track to meet global anaemia reduction targets: A Lancet Haematology Commission. The Lancet Haematology. https://doi.org/10.1016/S2352-3026(25)00146-2

4. Badura, K., Wieczernik, P., Biernat, J., & Krasowska-Kwiecień, A. (2024). Anemia of chronic kidney disease—A narrative review. Biomedicines, 12(6), 1191. https://doi.org/10.3390/biomedicines12061191

5. Babitt, J. L., & Lin, H-Y. (2012). Mechanisms of anemia in chronic kidney disease. Journal of the American Society of Nephrology, 23(10), 1631–1634. https://doi.org/10.1681/ASN.2011111078

6. Barcellini, W. (2020). New insights in the pathogenesis and treatment of autoimmune hemolytic anemia. Journal of Clinical Medicine, 9(12), 3859. https://doi.org/10.3390/jcm9123859

7. Bhandari, S., Spencer, S., & UK Kidney Association Guideline Group. (2024). UK Kidney Association Clinical Practice Guideline for Anemia of Chronic Kidney Disease. UK Kidney Association.

8. Brooker, S., Hotez, P. J., & Bundy, D. A. P. (2008). Hookworm-related anaemia among pregnant women: A systematic review. PLoS Neglected Tropical Diseases, 2(9), e291. https://doi.org/10.1371/journal.pntd.0000291

9. Camaschella, C. (2019). Iron deficiency. Blood, 133(1), 30–39. https://doi.org/10.1182/blood-2018-05-815944

10. Cappellini, M. D., Comin-Colet, J., de Francisco, A., Dignass, A., Doehner, W., Lam, C. S. P., … Macdougall, I. C. (2017). Iron deficiency across chronic inflammatory conditions: International expert opinion. American Journal of Hematology, 92(10), 1068–1078. https://doi.org/10.1002/ajh.24820

11. D’Angelo, G. (2013). Role of hepcidin in the pathophysiology and diagnosis of anemia. Blood Research, 48(1), 10–15. https://doi.org/10.5045/br.2013.48.1.10

12. de las Cuevas Allende, R., Entrenas-Cortés, J., & Díez, J.-M. (2021). Anaemia of chronic diseases: Pathophysiology, diagnosis and treatment. Best Practice & Research Clinical Haematology, 34(3), 101–113. https://doi.org/10.1016/j.beha.2020.101113

13. Fenwick, A. (2012). The global burden of neglected tropical diseases. Public Health, 126(3), 233–236. https://doi.org/10.1016/j.puhe.2011.11.015

14. Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y-S., Domm, J., Eustace, B. K., … Corbacioglu, S. (2021). CRISPR-CAS9 gene editing for sickle cell disease and β-thalassemia. New England Journal of Medicine, 384(3), 252–260. https://doi.org/10.1056/NEJMoa2031054

15. Garbe, E., Andersohn, F., Bronder, E., Klimpel, A., Thomae, M., Schrezenmeier, H., … Salama, A. (2011). Drug-induced immune haemolytic anaemia. British Journal of Haematology, 154(5), 644–653. https://doi.org/10.1111/j.1365-2141.2011.08784.x

16. GBD 2021 Anaemia Collaborators. (2023). Global burden and trends in anaemia, 1990–2021. The Lancet Haematology, 10(7), e489–e514. https://doi.org/10.1016/S2352-3026(23)00160-6

17. Hotez, P. J., & Kamath, A. (2009). Neglected tropical diseases in sub-Saharan Africa. PLoS Neglected Tropical Diseases, 3(8), e412. https://doi.org/10.1371/journal.pntd.0000412

18. Kanter, J., Walters, M. C., Krishnamurti, L., Mapara, M. Y., Kwiatkowski, J. L., Abraham, A., … Esrick, E. B. (2022). Biologic efficacy of LentiGlobin for sickle cell disease. New England Journal of Medicine, 386(7), 617–628. https://doi.org/10.1056/NEJMoa2117175

19. Kassebaum, N. J., Jasrasaria, R., Naghavi, M., Wulf, S. K., Johns, N., Lozano, R., … Murray, C. J. L. (2014). A systematic analysis of global anemia burden. Blood, 123(5), 615–624. https://doi.org/10.1182/blood-2013-06-508325

20. KDIGO Anemia Work Group. (2021). KDIGO 2021 Clinical Practice Guideline for Anemia in CKD. Kidney International Supplements, 11(1), 1–142.

21. Kroot, J. J. C., Tjalsma, H., Fleming, R. E., & Swinkels, D. W. (2011). Hepcidin in human iron disorders: Diagnostic implications. Clinical Chemistry, 57(12), 1650–1669. https://doi.org/10.1373/clinchem.2009.140053

22. Kulik-Rechberger, B., Marchewka, Z., & Rechberger, T. (2024). Iron deficiency and anemia of inflammation. Annals of Agricultural and Environmental Medicine, 31(1), 19–27. https://doi.org/10.26444/aaem/171121

23. Langer, A. L., & Ginzburg, Y. Z. (2017). Hepcidin–ferroportin axis in anemia of chronic inflammation. Hematology, 22(8), 607–616. https://doi.org/10.1080/10245332.2017.1329488

24. Menendez, C., Fleming, A. F., & Alonso, P. L. (2000). Malaria-related anemia. Parasitology Today, 16(11), 469–476. https://doi.org/10.1016/S0169-4758(00)01774-9

25. Mishra, A. K., & Tiwari, A. (2013). Iron overload in β-thalassemia. Maedica, 8(4), 328–332.

26. Morceau, F., Dicato, M., & Diederich, M. (2009). Cytokine-mediated anemia. Mediators of Inflammation, 2009, 405016. https://doi.org/10.1155/2009/405016

27. National Comprehensive Cancer Network. (2024). NCCN Guideline: Cancer- and Chemotherapy-Induced Anemia (Version 1.2024). NCCN.

28. Nemeth, E., & Ganz, T. (2022). Hepcidin and iron in health and disease. Annual Review of Medicine, 73, 527–540. https://doi.org/10.1146/annurev-med-042220-020836

29. Öneç, K., Altun, G., Özdemir Aytekin, Ş., Davran, F., & Öneç, B. (2025). ERFE, hepcidin and erythropoietin in CKD. Journal of Clinical Medicine, 14(21), 7789. https://doi.org/10.3390/jcm14217789

30. Pfeffer, M. A., Burdmann, E. A., Chen, C-Y., Cooper, M. E., de Zeeuw, D., Eckardt, K-U., … Parfrey, P. (2009). Darbepoetin alfa in type 2 diabetes and CKD. New England Journal of Medicine, 361(21), 2019–2032. https://doi.org/10.1056/NEJMoa0907845

31. Pinto, V. M., & Forni, G. L. (2020). Management of iron overload in β-thalassemia. International Journal of Molecular Sciences, 21(22), 8771. https://doi.org/10.3390/ijms21228771

32. Provenzano, R., Besarab, A., Sun, C-H., Diamond, S. A., Durham, J. H., Cangiano, J. L., … Macdougall, I. C. (2016). Oral HIF-PH inhibitor roxadustat for anemia in CKD. Clinical Journal of the American Society of Nephrology, 11(6), 982–991. https://doi.org/10.2215/CJN.06820615

33. Safiri, S., Kolahi, A-A., Noori, M., Nejadghaderi, S. A., Sullman, M. J. M., … Vos, T. (2021). Burden of anemia in 204 countries. Journal of Hematology & Oncology, 14, 185. https://doi.org/10.1186/s13045-021-01202-2

34. Sangkhae, V., & Nemeth, E. (2017). Regulation of hepcidin. Advances in Nutrition, 8(1), 126–136. https://doi.org/10.3945/an.116.013961

35. Singh, A. K., Szczech, L., Tang, K. L., Barnhart, H., Sapp, S., Wolfson, M., & Reddan, D. (2006). Correction of anemia with epoetin alfa. New England Journal of Medicine, 355(20), 2085–2098. https://doi.org/10.1056/NEJMoa065485

36. Soares, M. P., & Weiss, G. (2015). The iron age of host–microbe interactions. EMBO Reports, 16(11), 1482–1500. https://doi.org/10.15252/embr.201540425

37. Steinbicker, A. U., & Muckenthaler, M. U. (2013). Systemic iron homeostasis in iron disorders. Nutrients, 5(8), 3034–3061. https://doi.org/10.3390/nu5083034

38. Taher, A. T., Musallam, K. M., & Cappellini, M. D. (2021). β-Thalassemias. New England Journal of Medicine, 384(8), 727–743. https://doi.org/10.1056/NEJMra2021838

39. Townsley, D. M., Dumitriu, B., & Young, N. S. (2014). Aplastic anemia diagnosis and treatment. Mayo Clinic Proceedings, 89(11), 1645–1659. https://doi.org/10.1016/j.mayocp.2014.07.010

40. Weatherall, D. J. (2010). Thalassemia as a global health problem. Annals of the New York Academy of Sciences, 1202(1), 17–23. https://doi.org/10.1111/j.1749-6632.2010.05546.x

41. Weatherall, D. J. (2011). The inherited disorders of haemoglobin. Indian Journal of Medical Research, 134(4), 493–497.

42. Weiss, G., Ganz, T., & Goodnough, L. T. (2019). Anemia of inflammation. Blood, 133(1), 40–50. https://doi.org/10.1182/blood-2018-06-856500

43. Wiciński, M., Liczner, G., Cadelski, K., Kołnierzak, T., Nowaczewska, M., & Malinowski, B. (2020). Anemia of chronic diseases: Wider diagnostics. Nutrients, 12(6), 1784. https://doi.org/10.3390/nu12061784

44. World Health Organization. (2020). WHO guideline on the use of ferritin concentrations to assess iron status. WHO.

45. World Health Organization. (2024). Haemoglobin concentrations for diagnosing anaemia and assessing severity: 2024 update. WHO.

46. Young, N. S. (2018). Aplastic anemia. New England Journal of Medicine, 379(17), 1643–1656. https://doi.org/10.1056/NEJMra1413485

47. Pinto, V. M., & Forni, G. L. (2020). Management of iron overload in beta-thalassemia. International Journal of Molecular Sciences, 21(22), 8771. https://doi.org/10.3390/ijms21228771

48. Provenzano, R., Besarab, A., Sun, C-H., Diamond, S. A., Durham, J. H., Cangiano, J. L., … Macdougall, I. C. (2016). Roxadustat in anemia associated with CKD. Clinical Journal of the American Society of Nephrology, 11(6), 982–991. https://doi.org/10.2215/CJN.06820615

49. Pinto, V. M., & Forni, G. L. (2020). Management of iron overload. International Journal of Molecular Sciences, 21(22), 8771. https://doi.org/10.3390/ijms21228771

50. World Health Organization. (2024). Haemoglobin concentrations for the diagnosis of anaemia: 2024 update. WHO.

Downloads

Published

2025-11-16

How to Cite

Disease-Associated Anemia: An Integrated Review of Pathophysiology, Diagnosis, and Therapeutic Implications. (2025). Journal of Tropical Pharmacy and Chemistry , 9(2), 233-239. https://doi.org/10.30872/jtpc.v9i2.310

Similar Articles

21-30 of 45

You may also start an advanced similarity search for this article.