The importance of spleen, spleen iron, and splenectomy for determining total body iron load, ferrikinetics, and iron toxicity in thalassemia major patients

Toxicology Mechanisms and Methods

Volumn 23, Issue 1, 2013, Pages 34-41

  Kolnagou, Annita ^a   Michaelides, Yiannis ^a   Kontoghiorghe, Christina N ^a   Kontoghiorghes, George J ^a  

^a Postgraduate Research Institute of Science Technology Environment and Medicine Limassol   (Cyprus)

Author keywords

Chelation therapy; Liver iron; Spleen size and iron; Thalassemia iron overload; Total body iron

Indexed keywords

DEFERIPRONE; DEFEROXAMINE; FERRITIN; HEMOGLOBIN; IRON;

ADULT; ARTICLE; ERYTHROCYTE TRANSFUSION; FEMALE; FERRITIN BLOOD LEVEL; HEART DISEASE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HUMAN TISSUE; IRON CHELATION; IRON STORAGE; KINETICS; LIVER BIOPSY; LIVER SIZE; MAJOR CLINICAL STUDY; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; SPLEEN; SPLEEN BIOPSY; SPLEEN SIZE; SPLENECTOMY; THALASSEMIA MAJOR; ULTRASOUND;

ADULT; BETA-THALASSEMIA; BIOPSY; BODY BURDEN; CHELATION THERAPY; FEMALE; HUMANS; IRON; IRON OVERLOAD; LIVER; MAGNETIC RESONANCE IMAGING; MALE; ORGAN SIZE; RETROSPECTIVE STUDIES; SPLEEN; SPLENECTOMY; YOUNG ADULT;

EID: 84871410780     PISSN: 15376516     EISSN: 15376524     Source Type: Journal    
DOI: 10.3109/15376516.2012.735278     Document Type: Article

References (37)

1. Aessopos A, Farmakis D, Deftereos S, Tsironi M, Polonifi A, Moyssakis I, Diamanti-Kandaraki E, Papalambros E. 2005. Cardiovascular effects of splenomegaly and splenectomy in beta-thalassemia. Ann Hematol 84:353-357. (Pubitemid 40823347)
2. Aldouri MA, Wonke B, Hoffbrand AV, Flynn DM, Laulicht M, Fenton LA, Scheuer PJ, Kibbler CC, Allwood CA, Brown D. 1987. Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. J Clin Pathol 40:1353-1359. (Pubitemid 18015269)
3. Angelucci E, Brittenham GM, McLaren CE, Ripalti M, Baronciani D, Giardini C, Galimberti M, Polchi P, Lucarelli G. 2000. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med 343:327-331. (Pubitemid 30616698)
4. Angelucci E, Muretto P, Lucarelli G, Ripalti M, Baronciani D, Erer B, Galimberti M, Giardini C, Gaziev D, Polchi P. 1997. Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients. Blood 90:994-998. (Pubitemid 27314132)
5. Aydinok Y, Bayraktaroglu S, Yildiz D, Alper H. 2011. Myocardial iron loading in patients with thalassemia major in Turkey and the potential role of splenectomy in myocardial siderosis. J Pediatr Hematol Oncol 33:374-378.
6. Buja LM, Roberts WC. 1971. Iron in the heart. Etiology and clinical significance. Am J Med 51:209-221.
7. Brewer CJ, Coates TD, Wood JC. 2009. Spleen R2 and R2* in ironoverloaded patients with sickle cell disease and thalassemia major. J Magn Reson Imaging 29:357-364.
8. Brock JH, Licéaga J, Arthur HM, Kontoghiorghes GJ. 1990. Effect of novel 1-alkyl-3-hydroxy-2-methylpyrid-4-one chelators on uptake and release of iron from macrophages. Am J Hematol 34:21-25. (Pubitemid 20139482)
9. Drakonaki EE, Maris TG, Papadakis A, Karantanas AH. 2007. Bone marrow changes in beta-thalassemia major: quantitative MR imaging findings and correlation with iron stores. Eur Radiol 17:2079-2087. (Pubitemid 47097466)
10. Drakonaki EE, Maris TG, Maragaki S, Klironomos V, Papadakis A, Karantanas AH. 2010. Deferoxamine versus combined therapy for chelating liver, spleen and bone marrow iron in beta-thalassemic patients: a quantitative magnetic resonance imaging study. Hemoglobin 34:95-106.
11. Farmaki K, Tzoumari I, Pappa C, Chouliaras G, Berdoukas V. 2010. Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br J Haematol 148:466-475.
12. Fischer R, Harmatz PR (2009). Non-invasive assessment of tissue iron overload. Hematology Am Soc Hematol Educ Program, 215-221.
13. Fischer R, Tiemann CD, Engelhardt R, Nielsen P, Dürken M, Gabbe EE, Janka GE. 1999. Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry. Am J Hematol 60:289-299. (Pubitemid 29160089)
14. Fiorelli G, Fargion S, Piperno A, Battafarano N, Cappellini MD. 1990. Iron metabolism in thalassemia intermedia. Haematologica 75 Suppl 5:89-95. (Pubitemid 20359675)
15. Forni GL, Balocco M, Cremonesi L, Abbruzzese G, Parodi RC, Marchese R. 2008. Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation. Mov Disord 23: 904-907.
16. Green R, Charlton R, Seftel H, Bothwell T, Mayet F, Adams B, Finch C, Layrisse M. 1968. Body iron excretion in man: a collaborative study. Am J Med 45:336-353.
17. Hackett S, Chua-anusorn W, Pootrakul P, St Pierre TG. 2007. The magnetic susceptibilities of iron deposits in thalassaemic spleen tissue. Biochim Biophys Acta 1772:330-337.
18. Kolnagou A, Natsiopoulos K, Kleanthous M, Ioannou A, Kontoghiorghes GJ. 2012. Liver iron and serum ferritin levels are misleading for estimating cardiac, pancreatic, splenic and total body iron load in thalassemia patients: factors influencing the heterogenic distribution of excess storage iron in organs as identified by MRI T2*. Toxicol Mech Methods (in press).
19. Kolnagou A, Yazman D, Economides C, Eracleous E, Kontoghiorghes GJ. 2009. Uses and limitations of serum ferritin, magnetic resonance imaging T2 and T2* in the diagnosis of iron overload and in the ferrikinetics of normalization of the iron stores in thalassemia using the International Committee on Chelation deferiprone/deferoxamine combination protocol. Hemoglobin 33:312-322.
20. Kolnagou A, Economides C, Eracleous E, Kontoghiorghes GJ. 2008. Long term comparative studies in thalassemia patients treated with deferoxamine or a deferoxamine/deferiprone combination. Identification of effective chelation therapy protocols. Hemoglobin 32:41-47. (Pubitemid 351264511)
21. Kolnagou A, Kontoghiorghes GJ. 2010. New golden era of chelation therapy in thalassaemia: the achievement and maintenance of normal range body iron stores. Br J Haematol 150:489-490; author reply 491.
22. Kolnagou A, Kleanthous M, Kontoghiorghes GJ. 2010. Reduction of body iron stores to normal range levels in thalassaemia by using a deferiprone/ deferoxamine combination and their maintenance thereafter by deferiprone monotherapy. Eur J Haematol 85:430-438.
23. Kontoghiorghes GJ. 1994. Compliance with iron-chelation treatment after bone marrow transplantation. Lancet 343:604-605. (Pubitemid 24066397)
24. Kontoghiorghes GJ. 2009. Prospects for introducing deferiprone as potent pharmaceutical antioxidant. Front Biosci (Elite Ed) 1:161-178.
25. Kontoghiorghes GJ, Kolnagou A. 2005. Molecular factors and mechanisms affecting iron and other metal excretion or absorption in health and disease: the role of natural and synthetic chelators. Curr Med Chem 12:2695-2709. (Pubitemid 41601568)
26. Kontoghiorghes GJ, Eracleous E, Economides C, Kolnagou A. 2005. Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations. Curr Med Chem 12:2663-2681. (Pubitemid 41601566)
27. Kontoghiorghes GJ, Neocleous K, Kolnagou A. 2003. Benefits and risks of deferiprone in iron overload in Thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Saf. 26:553-584. (Pubitemid 36724096)
28. Limenta LM, Jirasomprasert T, Jittangprasert P, Wilairat P, Yamanont P, Chantharaksri U, Fucharoen S, Morales NP. 2011. Pharmacokinetics of deferiprone in patients with ß-thalassaemia: impact of splenectomy and iron status. Clin Pharmacokinet 50:41-50.
29. Mostert LJ, Van Dorst JA, Koster JF, Van Eijk HG, Kontoghiorghes GJ. 1987. Free radical and cytotoxic effects of chelators and their iron complexes in the hepatocyte. Free Radic Res Commun 3:379-388.
30. Olgar S, Kara A, Hicyilmaz H, Balta N, Canatan D. 2010. Evaluation of angiogenesis with vascular endothelial growth factor in patients with thalassemia major. Pediatr Int 52:247-251.
31. Ooi GC, Khong PL, Chan GC, Chan KN, Chan KL, Lam W, Ng I, Ha SY. 2004. Magnetic resonance screening of iron status in transfusiondependent beta-thalassaemia patients. Br J Haematol 124:385-390. (Pubitemid 38167991)
32. Oshiro S, Morioka MS, Kikuchi M. 2011. Dysregulation of iron metabolism in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Adv Pharmacol Sci 2011:378278.
33. Papakonstantinou O, Drakonaki EE, Maris T, Vasiliadou A, Papadakis A, Gourtsoyiannis N. 2006. MR imaging of spleen in beta-thalassemia major. Abdom Imaging.
34. Papakonstantinou O, Alexopoulou E, Economopoulos N, Benekos O, Kattamis A, Kostaridou S, Ladis V, Efstathopoulos E, Gouliamos A, Kelekis NL. 2009. Assessment of iron distribution between liver, spleen, pancreas, bone marrow, and myocardium by means of R2 relaxometry with MRI in patients with beta-thalassemia major. J Magn Reson Imaging 29:853-859.
35. Ricchi P, Ammirabile M, Costantini S, Di Matola T, Verna R, Diano A, Foglia MC, Spasiano A, Cinque P, Prossomariti L. 2012. 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 91:905-909.
36. Savva A. 1974. Human Anatomy. Aristotelium University of Thessaloniki: Greece. Omega Edition.
37. Vreugdenhil G, Kontoghiorghes GJ, Van Eijk HG, Swaak AJ. 1991. Impaired erythropoietin responsiveness to the anaemia in rheumatoid arthritis. A possible inverse relationship with iron stores and effects of the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Clin Exp Rheumatol 9:35-40.