The correlation between ineffective erythropoiesis biomarkers and development of extramedullary hematopoiesis in patients with thalassemia
Main Article Content
Keywords
Ineffective erythropoiesis biomarkers, thalassemia, extramedullary erythropoiesis
Abstract
Introduction: Extramedullary hematopoiesis (EMH) is one of the main complications in patients with thalassemia in compensation for the underlying ineffective erythropoiesis. This study aimed to evaluate the association between ineffective erythropoiesis biomarkers and EMH in patients with thalassemia.
Methods: A cross-sectional study of thalassemia patients aged >18 years old at Srinagarind Hospital was performed. Phosphatidylserine-exposed red blood cells (PS-exposed RBCs) were studied by flow cytometry. The levels of growth differentiation factor-15 (GDF15) and soluble transferrin receptor (sTfR) levels were determined using ELISA.
Results: One hundred and thirty-one patients were enrolled. EMH was found in 34 patients (26.0%). EMH was more prevalent among patients with β-thalassemia as compared to those with α-thalassemia (36.4% vs. 4.7%). The levels of GDF15 and sTfR were different between the two groups and indicated a greater degree of ineffective erythropoiesis in β-thalassemia patients. The levels of PS-exposed RBCs showed a modest correlation with EMH. Advanced age and the PS-exposed RBC levels had a statistical significance associated with EMH.
Conclusions: Advanced age and high PS-exposed RBC levels are associated with EMH in thalassemia. PS-exposed RBCs showed a modest correlation with EMH and may be used to predict the development of EMH in thalassemia.
Downloads
Abstract 477
PDF Downloads 314
HTML Downloads 147
References
2. Teawtrakul N, Chansung K, Sirijerachai C, Pongudom S, Jetsrisuparb A. A Clinical Risk Score for Predicting Paraspinal Extramedullary Hematopoiesis in Patients with Thalassemia: The KKU-EMH Score. J Med Assoc Thai. 2017;100:389.
3. Schrier SL. Thalassemia: pathophysiology of red cell changes. Annu Rev Med. 1994;45:211–18.
4. Zwaal RFA, Comfurius P, Bevers EM. Surface exposure of phosphatidylserine in pathological cells. Cell Mol Life Sci CMLS. 2005;62:971–88.
5. Boas FE, Forman L, Beutler E. Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia. Proc Natl Acad Sci U S A. 1998;95:3077–81.
6. Singer ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H. Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol. 2006;81:670–75.
7 . Tanno T, Bhanu NV, Oneal PA, Goh S-H, Staker P, Lee YT, Moroney JW, Reed CH, Luban NLC, Wang R-H, Eling TE, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13:1096–1101.
8. Musallam KM, Taher AT, Duca L, Cesaretti C, Halawi R, Cappellini MD. Levels of growth differentiation factor-15 are high and correlate with clinical severity in transfusion-independent patients with β thalassemia intermedia. Blood Cells Mol Dis. 2011;47:232–34.
9. R’zik S, Loo M, Beguin Y. Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels. Haematologica. 2001;86:244–51.
10. Cazzola M, Beguin Y, Bergamaschi G, Guarnone R, Cerani P, Barella S, Cao A, Galanello R. Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis. Br J Haematol. 1999;106:752–55.
11. Ricchi P, Ammirabile M, Costantini S, Di Matola T, Verna R, Diano A, Foglia MC, Spasiano A, Cinque P, Prossomariti L. A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study. Ann Hematol. 2012;91:905–9.
12. Rasekhi AR, Naderifar M, Bagheri MH, Shahriari M, Foroutan H, Karimi M, Nabavizadeh SA. Radiofrequency ablation of the spleen in patients with thalassemia intermedia: a pilot study. AJR Am J Roentgenol. 2009;192:1425–29.
13. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, Saned M-S, El-Chafic A-H, Fasulo MR, Cappellini MD. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115:1886–92.
14. Haidar R, Mhaidli H, Taher AT. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deform Soc Eur Sect Cerv Spine Res Soc. 2010;19:871–78.
15. Pattanapanyasat K, Noulsri E, Fucharoen S, Lerdwana S, Lamchiagdhase P, Siritanaratkul N, Webster HK. Flow cytometric quantitation of red blood cell vesicles in thalassemia. Cytometry B Clin Cytom. 2004;57:23–31.
16. Yamsri S, Sanchaisuriya K, Fucharoen G, Sae-Ung N, Ratanasiri T, Fucharoen S. Prevention of severe thalassemia in northeast Thailand: 16 years of experience at a single university center. Prenat Diagn. 2010;30:540–46.
17. Chansai S, Fucharoen S, Fucharoen G, Jetsrisuparb A, Chumpia W. Elevations of Thrombotic Biomarkers in Hemoglobin H Disease. Acta Haematol. 2018;139:47–51.
18. Atichartakarn V, Angchaisuksiri P, Aryurachai K, Onpun S, Chuncharunee S, Thakkinstian A, Atamasirikul K. Relationship between hypercoagulable state and erythrocyte phosphatidylserine exposure in splenectomized haemoglobin E/beta-thalassaemic patients. Br J Haematol. 2002;118:893–98.
19. Atichartakarn V, Likittanasombat K, Chuncharunee S, Chandanamattha P, Worapongpaiboon S, Angchaisuksiri P, Aryurachai K. Pulmonary arterial hypertension in previously splenectomized patients with beta-thalassemic disorders. Int J Hematol. 2003;78:139–45.
20. Ibrahim HA, Fouda MI, Yahya RS, Abousamra NK, Abd Elazim RA. Erythrocyte phosphatidylserine exposure in β-thalassemia. Lab Hematol Off Publ Int Soc Lab Hematol. 2014;20:9–14.
21. Libani IV, Guy EC, Melchiori L, Schiro R, Ramos P, Breda L, Scholzen T, Chadburn A, Liu Y, Kernbach M, Baron-Lühr B, Porotto M, de Sousa M, Rachmilewitz EA, Hood JD, Cappellini MD, Giardina PJ, Grady RW, Gerdes J, Rivella S. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood. 2008;112:875–85.
22. Kaddah AM, Abdel-Salam A, Farhan MS, Ragab R. Serum Hepcidin as a Diagnostic Marker of Severe Iron Overload in Beta-thalassemia Major. Indian J Pediatr. 2017;84:745–50.
23. Porter JB, Cappellini MD, Kattamis A, Viprakasit V, Musallam KM, Zhu Z, Taher AT. Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions. Br J Haematol. 2017;176:288–99.
24. Huang Y, Lei Y, Liu R, Liu J, Yang G, Xiang Z, Liang Y, Lai Y. Imbalance of erythropoiesis and iron metabolism in patients with thalassemia. Int J Med Sci. 2019;16:302–10.
25. Gardenghi S, Grady RW, Rivella S. Anemia, ineffective erythropoiesis, and hepcidin: interacting factors in abnormal iron metabolism leading to iron overload in β-thalassemia. Hematol Oncol Clin North Am. 2010;24:1089–1107.
26. Bradley MJ, Metreweli C. Ultrasound appearances of extramedullary haematopoiesis in the liver and spleen. Br J Radiol. 1990;63:816–18.
27. Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of β thalassaemia intermedia. Br J Haematol. 2011;152:512–23.
28. Taher A, Isma’eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis. 2006;37:12–20.
29. Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol. 2009;16:187–94.
30. Ricchi P, Meloni A, Spasiano A, Neri MG, Gamberini MR, Cuccia L, Caruso V, Gerardi C, D’Ascola DG, Rosso R, Campisi S, Rizzo M, Terrazzino F, Vangosa AB, Chiodi E, Missere M, Mangione M, Positano V, Pepe A. Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients. Am J Hematol. 2015;90:1008–12.
31. Ricchi P, Ammirabile M, Spasiano A, Costantini S, Di Matola T, Pepe A, Cinque P, Pagano L, Casale M, Filosa A, Prossomariti L. Extramedullary haematopoiesis correlates with genotype and absence of cardiac iron overload in polytransfused adults with thalassaemia. Blood Transfus Trasfus Sangue. 2014;12 Suppl 1:s124-130.
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.