How We Manage Iron Overload in Sickle Cell Patients

Overview

Journal Br J Haematol

Specialty Hematology

Date 2017 Mar 16

PMID 28295188

Citations 30

Authors

Thomas D Coates

John C Wood

Affiliations

Soon will be listed here.

Abstract

Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging.

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References

Wood J, Pressel S, Rogers Z, Odame I, Kwiatkowski J, Lee M . Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: baseline results from the TWiTCH trial. Am J Hematol. 2015; 90(9):806-10. PMC: 4546569. DOI: 10.1002/ajh.24089. View

Farmaki K, Tzoumari I, Pappa C, Chouliaras G, Berdoukas V . Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major. Br J Haematol. 2009; 148(3):466-75. DOI: 10.1111/j.1365-2141.2009.07970.x. View

Porter J, Elalfy M, Taher A, Aydinok Y, Chan L, Lee S . Efficacy and safety of deferasirox at low and high iron burdens: results from the EPIC magnetic resonance imaging substudy. Ann Hematol. 2012; 92(2):211-9. PMC: 3542426. DOI: 10.1007/s00277-012-1588-x. View

Darbari D, Kple-Faget P, Kwagyan J, Rana S, Gordeuk V, Castro O . Circumstances of death in adult sickle cell disease patients. Am J Hematol. 2006; 81(11):858-63. DOI: 10.1002/ajh.20685. View

Fernandes J, Loggetto S, Verissimo M, Fertrin K, Baldanzi G, Fioravante L . A randomized trial of amlodipine in addition to standard chelation therapy in patients with thalassemia major. Blood. 2016; 128(12):1555-61. DOI: 10.1182/blood-2016-06-721183. View

Kolnagou A, Kontoghiorghes G . New golden era of chelation therapy in thalassaemia: the achievement and maintenance of normal range body iron stores. Br J Haematol. 2010; 150(4):489-90. DOI: 10.1111/j.1365-2141.2010.08229.x. View

Tsouana E, Kaya B, Gadong N, Hemmaway C, Newell H, Simmons A . Deferasirox for iron chelation in multitransfused children with sickle cell disease; long-term experience in the East London clinical haemoglobinopathy network. Eur J Haematol. 2014; 94(4):336-42. DOI: 10.1111/ejh.12435. View

Nemeth E, Valore E, Territo M, Schiller G, Lichtenstein A, Ganz T . Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2002; 101(7):2461-3. DOI: 10.1182/blood-2002-10-3235. View

Vitrano A, Calvaruso G, Tese L, Gioia F, Cassara F, Campisi S . Real-life experience with liver iron concentration R2 MRI measurement in patients with hemoglobinopathies: baseline data from LICNET. Eur J Haematol. 2016; 97(4):361-70. DOI: 10.1111/ejh.12740. View

10.

Sahlstedt L, Ebeling F, von Bonsdorff L, Parkkinen J, Ruutu T . Non-transferrin-bound iron during allogeneic stem cell transplantation. Br J Haematol. 2001; 113(3):836-8. DOI: 10.1046/j.1365-2141.2001.02820.x. View

11.

Aydinok Y, Kattamis A, Cappellini M, El-Beshlawy A, Origa R, Elalfy M . Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload. Blood. 2015; 125(25):3868-77. PMC: 4490296. DOI: 10.1182/blood-2014-07-586677. View

12.

Yawn B, Buchanan G, Afenyi-Annan A, Ballas S, Hassell K, James A . Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014; 312(10):1033-48. DOI: 10.1001/jama.2014.10517. View

13.

Ware R, Davis B, Schultz W, Brown R, Aygun B, Sarnaik S . Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2015; 387(10019):661-670. PMC: 5724392. DOI: 10.1016/S0140-6736(15)01041-7. View

14.

Gomber S, Jain P, Sharma S, Narang M . Comparative Efficacy and Safety of Oral Iron Chelators and their Novel Combination in Children with Thalassemia. Indian Pediatr. 2016; 53(3):207-10. DOI: 10.1007/s13312-016-0821-4. View

15.

Kolnagou A, Kleanthous M, Kontoghiorghes G . 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. 2010; 85(5):430-8. DOI: 10.1111/j.1600-0609.2010.01499.x. View

16.

Breda L, Rivella S . Modulators of erythropoiesis: emerging therapies for hemoglobinopathies and disorders of red cell production. Hematol Oncol Clin North Am. 2014; 28(2):375-86. PMC: 3970239. DOI: 10.1016/j.hoc.2013.12.001. View

17.

Powars D, Chan L, Hiti A, Ramicone E, Johnson C . Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005; 84(6):363-376. DOI: 10.1097/01.md.0000189089.45003.52. View

18.

Detterich J, Kato R, Rabai M, Meiselman H, Coates T, Wood J . Chronic transfusion therapy improves but does not normalize systemic and pulmonary vasculopathy in sickle cell disease. Blood. 2015; 126(6):703-10. PMC: 4528063. DOI: 10.1182/blood-2014-12-614370. View

19.

Koren A, Fink D, Admoni O, Tennenbaum-Rakover Y, Levin C . Non-transferrin-bound labile plasma iron and iron overload in sickle-cell disease: a comparative study between sickle-cell disease and beta-thalassemic patients. Eur J Haematol. 2009; 84(1):72-8. DOI: 10.1111/j.1600-0609.2009.01342.x. View

20.

Inati A, Musallam K, Wood J, Sheikh-Taha M, Daou L, Taher A . Absence of cardiac siderosis by MRI T2* despite transfusion burden, hepatic and serum iron overload in Lebanese patients with sickle cell disease. Eur J Haematol. 2009; 83(6):565-71. DOI: 10.1111/j.1600-0609.2009.01345.x. View