D. Weatherall, M. Cappellini, and . Thalassaemia, Disponible sur: https://www.has-sante.fr/portail/upload/docs/application/pdf Disponible sur, BIBLIOGRAPHIE 1. Pnds_thalassemies_final_web.pdf [Internet]. [cité 28 déc 2017 The Lancet [Internet]. 31 juill 2017, p.11, 2008.

P. Joly, C. Pondarre, and C. Badens, Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects, Ann Biol Clin nov, vol.72, issue.16, pp.639-68, 2014.

, Disponible sur: https://www-sciencedirect-com.docelec.u-bordeaux.fr/science, Les thalassémies en 2016 -ScienceDirect [Internet]. [cité 13 févr, 2018.

N. Couque, E. Trawinski, and J. Elion, Génétique des maladies de l'hémoglobine. Rev Francoph Lab

, avr, vol.2016, issue.481, pp.49-60, 2016.

K. Bayanzay and L. Alzoebie, Reducing the iron burden and improving survival in transfusion-dependent thalassemia patients: current perspectives, Journal of Blood Medicine, vol.7, pp.159-69, 2016.
DOI : 10.2147/JBM.S61540

E. Kanavakis, J. Traeger-synodinos, S. Lafioniatis, C. Lazaropoulou, T. Liakopoulou et al., Genetic modifiers of the ?-haemoglobinopathies A rare example that coinheritance of a severe form of ?-thalassemia and ?-thalassemia interact in a " synergistic " manner to balance the phenotype of classic thalassemic syndromes Crielaard BJ, Rivella S. ?-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis Bone disease and skeletal complications in patients with ? thalassemia major, Les thalassémies en 2016 -ScienceDirect [Internet]. [cité 13 févr Disponible sur Thein SL al. [Symptomatic extramedullary haematopoiesis in ?-thalassemia: A retrospective single centre study], pp.357-66319, 2004.

Y. Ginzburg and S. Rivella, ?-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism):4321? 30. 15. Rivella S. The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia, Blood. 20 oct Blood Rev. avr, vol.11826, issue.16 1, pp.12-15, 2011.

E. Poggiali, E. Cassinerio, L. Zanaboni, M. Cappellini, P. Telfer et al., An update on iron chelation therapy Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major, 411?22. 17971?7. 18. Wood JC. Impact of iron assessment by MRI, pp.443-50, 2000.

G. Yang, R. Liu, P. Peng, L. Long, X. Zhang et al., How Early Can Myocardial Iron Overload Occur in Beta Thalassemia Major?, PLoS ONE, vol.379, issue.23, p.85379, 2014.
DOI : 10.1371/journal.pone.0085379.t002

P. Kirk, M. Roughton, J. Porter, J. Walker, M. Tanner et al., Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major, Circulation. 17 nov, vol.120, issue.20, 2009.

N. Olivieri and G. Brittenham, Iron-chelating therapy and the treatment of thalassemia

, 739?61. 22. Taher AT, Saliba AN. Iron overload in thalassemia: different organs at different rates. Hematol Am Soc Hematol Educ Program, févr, vol.892017, issue.31, pp.265-71, 1997.

J. Kwiatkowski, Current recommendations for chelation for transfusion-dependent thalassemia, Annals of the New York Academy of Sciences, vol.95, issue.1
DOI : 10.1111/ejh.12507

, Ann N Y Acad Sci. mars, vol.1368, issue.1, pp.107-121, 2016.

M. Cappellini, M. Bejaoui, L. Agaoglu, D. Canatan, M. Capra et al., Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood. 28 juill Depletion of excessive liver iron stores with desferrioxamine Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review, Br J Haematol. oct Transfusion oct, vol.1185847, issue.25210, pp.369-73, 1984.

S. Ansari, A. Azarkeivan, G. Miri-aliabad, S. Yousefian, T. Rostami et al., Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis, 159?64. 28. Pennell DJ, pp.3738-3782, 2006.

G. Pantalone, A. Maggio, A. Vitrano, M. Capra, L. Cuccia et al., Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in -thalassemia major patients Deferasirox for managing iron overload in people with thalassaemia, Hemoglobin. Cochrane Database Syst Rev, vol.358, issue.15, p.7476, 2011.

M. Cappellini, A. Cohen, A. Piga, M. Bejaoui, S. Perrotta et al., A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia, Blood, vol.107, issue.9, pp.3455-62, 2006.
DOI : 10.1182/blood-2005-08-3430

V. Osborne, M. Davies, D. Layton, S. Shakir, D. Pennell et al., Utilisation and Safety of Deferasirox: Results from an Observational Cohort Study in England Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study, Drug Saf. 10 oct Blood. 25 mars Am J Hematol. mai, vol.3311592, issue.5, pp.420-428, 2010.

B. Pham, L. Pennec, P. Rouger, and P. , Allo-immunisation anti-??rythrocytaire, Transfusion Clinique et Biologique, vol.19, issue.6
DOI : 10.1016/j.tracli.2012.06.007

, déc, vol.19, issue.6, pp.321-353, 2012.

F. Pirenne, P. Bartolucci, and A. Habibi, Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment, Transfusion Clinique et Biologique, vol.24, issue.3, pp.227-258, 2017.
DOI : 10.1016/j.tracli.2017.05.016

H. Schonewille, L. Van-de-watering, D. Loomans, and A. Brand, Red blood cell alloantibodies after transfusion: factors influencing incidence and specificity, Transfusion, vol.7, issue.2, pp.250-256, 2006.
DOI : 10.1046/j.1537-2995.1994.34294143938.x

H. Schonewille, L. Van-de-watering, D. Loomans, and A. Brand, Red blood cell alloantibodies after transfusion: factors influencing incidence and specificity, Transfusion, vol.7, issue.2, pp.250-256, 2006.
DOI : 10.1046/j.1537-2995.1994.34294143938.x

W. Bao, H. Zhong, X. Li, M. Lee, J. Schwartz et al., Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms. Transfusion (Paris) HLA-DRB1 alleles and Jk(a) immunization. Transfusion (Paris) Red cell alloimmunization in a diverse population of transfused patients with thalassaemia The incidence of development of irregular red cell antibodies in patients with sickle cell anemia Stochastic modeling of human RBC alloimmunization: evidence for a distinct population of immunologic responders Transfusion (Paris) Red cell alloimmunization in repeatedly transfused patients, ):379?89. 41. Reviron D,121?8. 43. Sarnaik S,2546?53. 45. Vichinsky E Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME), pp.249-52, 1986.

P. Hewitt, E. Macintyre, A. Devenish, S. Bowcock, and M. Contreras, A prospective study of the incidence of delayed haemolytic transfusion reactions following peri-operative blood transfusion, British Journal of Haematology, vol.5, issue.4, pp.541-545, 1988.
DOI : 10.1046/j.1537-2995.1984.24384225018.x

A. Française-de and S. , Transfusion de globules rouges homologues : produits, indications, alternatives. Ann Fr D?Anesthésie Réanimation. 1 janv, pp.67-81, 2003.

K. Musallam, M. Karimi, A. El-beshlawy, K. Belhoul, and S. Daar, Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study, Ordonnance n° 2012-785 du 31 mai 2012 portant extension et adaptation du code de l'action sociale et des familles au Département de Mayotte. 50. Taher AT, pp.1886-92, 2010.

E. Ferro, G. Visalli, L. Rosa, M. Civa, R. Papa et al., The role of anaemia in oxidative and genotoxic damage in transfused ??-thalassaemic patients, Hematology, vol.95, issue.3, pp.183-91, 2017.
DOI : 10.1182/blood-2011-01-258467

I. Maaloul, O. Laaroussi, I. Jedidi, L. Sfaihi, S. Kmiha et al., Prise en charge thérapeutique des patients atteints de bêta-thalassémie majeure dans un service de pédiatrie du sud tunisien : à propos de 26 cas Les thalassémies en 2016. Rev Francoph Lab, Transfus Clin Biol. 1 févr, vol.252016, issue.1481324, pp.67-75, 2000.

E. Ferro, G. Visalli, R. Civa, L. Rosa, M. et al., Oxidative damage and genotoxicity biomarkers in transfused and untransfused thalassemic subjects Alloimmunization in Sickle Cell Anemia and Transfusion of Racially Unmatched Blood Allo-immunisation anti-érythrocytaire post-transfusionnelle : analyse et suivi immunologique de patients receveurs de concentres érythrocytaires en Alsace durant la période, ):1829?37. 56. Vichinsky EP, pp.1617-1638, 1990.

O. Platt, S. Orkin, G. Dover, G. Beardsley, B. Miller et al., Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia., Journal of Clinical Investigation, vol.74, issue.2, pp.652-658, 1984.
DOI : 10.1172/JCI111464

S. Charache, M. Terrin, R. Moore, G. Dover, F. Barton et al., Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, 1317?22. 60, pp.2039-2084, 1995.

K. Musallam, A. Taher, M. Cappellini, V. Sankaran, V. Sankaran et al., Thalassemia: an overview of 50 years of clinical research XmnI polymorphism frequency in heterozygote beta thalassemia subjects and its relation to Fetal hemoglobin levels. Rev Bras Hematol E Hemoter):483. 64. Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin):a011643. 65. Hydroxyurea for lifelong transfusion-dependent ?-thalassemia: A meta-analysis: Pediatric Hematology and Oncology al. Transfusion independence and HMGA2 activation after gene therapy of human ?-thalassaemia, 1005?20. 63. Chinelato IS,318?22. 67. Rivella S. ?-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies, pp.418-448, 2010.

I. Libani, E. Guy, L. Melchiori, R. Schiro, P. Ramos et al., Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in ??-thalassemia, Blood, vol.112, issue.3, pp.875-85, 2008.
DOI : 10.1182/blood-2007-12-126938

S. Guo, C. Casu, S. Gardenghi, S. Booten, M. Aghajan et al., Reducing TMPRSS6 ameliorates hemochromatosis and ?-thalassemia in mice Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis, ):1531?41. 703829?36. 71. Prise en charge actuelle des thalassémies intermédiaires -ScienceDirect [Internet]. [cité 12 mars Disponible sur, 2012.

H. Li, A. Rybicki, S. Suzuka, V. Bonsdorff, L. Breuer et al., Transferrin therapy ameliorates disease in ??-thalassemic mice, Nature Medicine, vol.4, issue.2, pp.177-82, 2010.
DOI : 10.1172/JCI21982

, Annexe 1

M. Madame,

, Votre enfant est suivi, au sein du service de pédiatrie au CHM

, Nous allons modifier notre pratique selon les recommandations du Centre National de Référence (CNR) : la fréquence des transfusions va être augmentée dans le but d'éviter les conséquences à long terme de la maladie

, Nous réalisons une étude chez les enfants atteints de Béta-Thalassémie majeure

, Pourquoi cette étude ?

, Le Centre National de Référence des maladies rares des globules rouges préconise un seuil transfusionnel à 9.5-10.5 g/dl d'hémoglobine pré-transfusionnelle chez tous les enfants atteints de Béta-Thalassémie majeure

. Hors,

, Quel est l'objet de cette recherche ?

, L'objectif principal est d'évaluer l'impact de cette nouvelle pratique sur le plan organique

, Comment va se dérouler la recherche ?

, Afin d'obtenir un seuil transfusionnel satisfaisant, votre enfant devra bénéficier d'une augmentation du nombre des transfusions

. Cela-signifie-qu, il devra venir à l'hôpital de jour toutes les 2 semaines pour un bilan sanguin et une transfusion pendant au moins 6 semaines

. La-période-d, intensification pourra être prolongée si le seuil pré-transfusionnel recommandé (9.5 à 10

, Durant cette période votre enfant bénéficiera comme prévu d'une surveillance de la ferritine sanguine, de l'IRM hépatique et l'IRM cardiaque

, Si vous ne désirez pas que votre enfant prenne part à cette recherche, il continuera à bénéficier de la meilleure prise en charge médicale possible, conformément aux connaissances actuelles

, Nous vous remercions de votre participation

C. Dr and M. Alice,

, Autorisation de mise sur le marché CGR: Culots de globules rouges CIHF: Concentration intra-hépatique en fer CHM: Centre hospitalier de Mayotte CRMR: Centre de Référence des Maladies Rares CSH: Cellules souches hématopoïétiques DFP, ALD: Affection longue durée AMM DEFERIPRONE DFO: DEFEROXAMINE DFX: DEFERASIROX EPP : Evaluation de Pratiques Profesionnelles HAS: Haute Autorité de Santé HbF

, HLA: Histocompability Leukocyte Antigen HPLC: High-Performance Liquid Chromatography IRM: Imagerie par Résonnance Magnétique PBH: Ponction-biopsie hépatique RCP : Réunion de concertation pluridisciplinaire SQUID: Superconducting QUantum Interference Device VHB: Virus de l'Hépatite B

, VHC: Virus de l'Hépatite C