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      When to consider transfusion therapy for patients with non-transfusion-dependent thalassaemia

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          Abstract

          Non-transfusion-dependent thalassaemia (NTDT) refers to all thalassaemia disease phenotypes that do not require regular blood transfusions for survival. Thalassaemia disorders were traditionally concentrated along the tropical belt stretching from sub-Saharan Africa through the Mediterranean region and the Middle East to South and South-East Asia, but global migration has led to increased incidence in North America and Northern Europe. Transfusionists may be familiar with β-thalassaemia major because of the lifelong transfusions needed by these patients. Although patients with NTDT do not require regular transfusions for survival, they may require transfusions in some instances such as pregnancy, infection or growth failure. The complications associated with NTDT can be severe if not properly managed, and many are directly related to chronic anaemia. Awareness of NTDT is important, and this review will outline the factors that should be taken into consideration when deciding whether to initiate and properly plan for transfusion therapy in these patients in terms of transfusion interval and duration of treatment.

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          The beta-thalassemias.

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            Non-transfusion-dependent thalassemias.

            Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.
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              Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study.

              Despite recent advances in understanding the pathophysiologic mechanisms behind the thalassemia intermedia (TI) phenotype, data on the effects of treatment are deficient. To provide such data, we evaluated 584 TI patients for the associations between patient and disease characteristics, treatment received, and the rate of complications. The most common disease-related complications were osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes mellitus were less frequently observed. On multivariate analysis, older age and splenectomy were independently associated with an increased risk of most disease-related complications. Transfusion therapy was protective for thrombosis, EMH, PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy was associated with an increased risk of endocrinopathy. Iron chelation therapy was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was associated with an increased risk of hypogonadism yet was protective for EMH, PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to the impact of age on complications in TI, and the beneficial role of splenectomy deserves revisiting. This study provides evidence that calls for prospective evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy in TI patients.
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                Author and article information

                Journal
                Vox Sang
                Vox Sang
                vox
                Vox Sanguinis
                John Wiley & Sons Ltd (Oxford, UK )
                0042-9007
                1423-0410
                January 2015
                07 October 2014
                : 108
                : 1
                : 1-10
                Affiliations
                [1 ]American University of Beirut Beirut, Lebanon
                [2 ]Siriraj Hospital, Mahidol University Bangkok, Thailand
                Author notes
                Correspondence: Ali T. Taher, Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236, Riad El Solh 1107 2020, Beirut, Lebanon, E-mail: ataher@ 123456aub.edu.lb , or, Vip Viprakasit, Department of Pediatrics and Thalassaemia Center, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, E-mail: vip.vip@ 123456mahidol.ac.th
                Article
                10.1111/vox.12201
                4302976
                25286743
                f4f3b010-31ea-4306-ba02-12783589b43a
                © 2014 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 February 2014
                : 17 July 2014
                : 05 August 2014
                Categories
                Review

                Hematology
                haemoglobin e/β thalassaemia,haemoglobin h disease,iron chelation,non-transfusion-dependent thalassaemia,red cell transfusion,β-thalassaemia intermedia

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