Side effect of deferiprone as iron chelator in patient with thalassemia
Abstract
Background There are currently three available iron chelators: deferoxamine (DFO), deferasirox (DFX) and deferiprone (DFP). In Dr. Cipto Mangunkusumo Hospital and Indonesia, in general, the accessibility of DFP for thalassemia patients has been adequate. Even though its efficacy in removing iron has been proven by countless studies, questions relating to its safety and possible side effects continue to be raised.
Objective To assess common side effects of DFP usage by an intensive literature search and compare them to that in a pediatric thalassemia patient, in order to determine if the child's symptoms in the were potentially caused by DFP.
Methods A literature search using MeSH terms was done in PubMed. Full copies of articles that fulfil the inclusion criteria, based on their title, abstract, and subject descriptors, were critically appraised using The Joanna Brigs Institute (JBI) critical appraisal tools.
Results A total of 10 research articles from 1998-2013 were deemed applicable to this study including: 2 case reports, 5 prospective cohort studies, 2 retrospective cohort studies, and 1 randomized control trial with a grand total of 1,026 samples.
Conclusion Side effects of DFP include: neutropenia, agranulocytosis, increased ALT, gastrointestinal problems, arthralgia or arthropathy, increased appetite or weight, thrombocytopenia, urine discoloration, as well as auditory and visual disturbances. Our case report patient's symptoms of gum bleeding and haemorrhagic mass are not related to her DFP consumption.
References
2 Cappellini MD, Bejaoui M, Agaoglu L, Porter J, Coates T, Jeng M, et al. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with ?-thalassemia. Clin Ther. 2007;29:909-17.
3 Kontoghiorghe CN, Kontoghiorghes GJ. New developments and controversies in iron metabolism and iron chelation therapy. World J Methodol. 2016;6:1-19.
4 Ceci A, Baiardi P, Felisi M, Cappellini MD, Carnelli V, De Sanctis V, et al. The safety and effectiveness of deferiprone in a large?scale, 3?year study in Italian patients. Br J Haematol. 2002;118:330-6.
5 Chand G, Chowdhury V, Manchanda A, Singh S. Deferiprone-induced arthropathy in thalassemia: MRI findings in a case. Indian J Radiol Imaging. 2009;19:155-7.
6 Choudhry V, Pati H, Saxena A, Malaviya A. Deferiprone, efficacy and safety. Indian J Pediatr. 2004;71:213-6.
7 Cohen A, Galanello R, Piga A, Vullo C, Tricta F. A multi?center safety trial of the oral iron chelator deferiprone. Ann N Y Acad Sci. 1998;850:223-6.
8 Ha SY, Chik KW, Ling SC, Lee AC, Luk CW, Lam CW, et al. A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong. Hemoglobin. 2006;30:263-74.
9 Hoffbrand AV, Al-Refaie F, Davis B, Siritanakatkul N, Jackson BF, Cochrane J, et al. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood. 1998;91:295-300.
10 Naithani R, Chandra J, Sharma S. Safety of oral iron chelator deferiprone in young thalassaemics. Eur J Haematol. 2005;74:217-20.
11 Tewari S, Tewari S, Sharma RK, Abrol P, Sen R. Necrotizing stomatitis: a possible periodontal manifestation of deferiprone-induced agranulocytosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108:e13-9.
12 Uygun V, Kurtoglu E. Iron-chelation therapy with oral chelators in patients with thalassemia major. Hematology. 2013;18:50-5.
13 Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the US population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-92.
14 Maggio A, Vitrano A, Capra M, Cuccia L, Gagliardotto F, Filosa A, et al. Long?term sequential deferiprone–deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial. Br J Haematol. 2009;145:245-54.
15 Masera N, Tavecchia L, Longoni DV, Maglia O, Biondi A, Masera G. Agranulocytosis due to deferiprone: a case report with cytomorphological and functional bone marrow examination. Blood Transfus. 2011;9:462-5.
16 Wanless IR, Sweeney G, Dhillon AP, Guido M, Piga A, Galanello R, et al. Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood. 2002;100:1566-9.
17 Berkovitch M, Laxer RM, Inman R, Koren G, Olivieri NF, Pritzker KP, et al. Arthropathy in thalassaemia patients receiving deferiprone. Lancet. 1994;343:1471-2.
18 El-Alfy MS, Sari TT, Chan LL, Tricta F, El-Beshlawy A. The tolerability, safety and efficacy of a new oral solution of deferiprone in children with transfusional iron overload. Blood. 2008 Nov 16;112:5373.
19 Ferriprox (deferiprone) [package insert]. Toronto (ON): Apotex Inc; 2011.
20 Olivieri NF, Buncic JR, Chew E, Gallant T, Harrison RV, Keenan N, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med. 1986;314:869-73.
21 Viprakasit V, Nuchprayoon I, Chuansumrit A, Torcharus K, Pongtanakul B, Laothamatas J, Srichairatanakool S, Pooliam J, Supajitkasem S, Suriyaphol P, Tanphaichitr VS. Deferiprone (GPO?L?ONE®) monotherapy reduces iron overload in transfusion?dependent thalassemias: 1?year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO?L?ONE; A001) from Thailand. Am J Hematol. 2013 Apr 1;88(4):251-60.
22 Joanna Briggs Institute, Joanna Briggs Institute. reviewers’ manual: 2011 edition. Adelaide: JBI. 2014.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Accepted 2017-12-15
Published 2018-01-05
