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According to the current understanding of NTDT, these clinical complications stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload, and hypercoagulability. The state of chronic anemia and hypoxia\u2014resulting from ineffective erythropoiesis and hemolysis\u2014leads to the expansion of the erythroid marrow and extramedullary hematopoiesis. The chronic ineffective erythropoiesis also triggers increased intestinal iron absorption and deposition in the liver and endocrine glands despite the lack of transfusional iron load. Patients with NTDT also have a higher incidence of thromboembolic disease, pulmonary hypertension, and silent cerebral ischemia. The treatment of NTDT relies on occasional or more frequent blood transfusions for certain indications (severe infection, pregnancy, and surgery), iron chelation therapy, splenectomy, and hydroxyurea. Splenectomy is no longer routinely performed in all patients with NTDT in light of its association with increased risk of NTDT\u2010related complications. This review focuses on the clinical morbidities associated with NTDT, summarizes the mainstays of treatment, and sheds light on future therapeutic directions in the field.<\/jats:p>","DOI":"10.1111\/nyas.13083","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T15:36:36Z","timestamp":1463499396000},"page":"82-94","source":"Crossref","is-referenced-by-count":27,"title":["Morbidities in non\u2010transfusion\u2010dependent thalassemia"],"prefix":"10.1111","volume":"1368","author":[{"given":"Antoine N.","family":"Saliba","sequence":"first","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali T.","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"829","article-title":"Thalassemia intermedia; cases in Negro siblings with unusual differences in minor hemoglobin components","volume":"23","author":"Pearson H.A.","year":"1964","journal-title":"Blood"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1959.02070010466011"},{"key":"e_1_2_6_4_1","first-page":"336","article-title":"Thalassemia intermedia complicated by hemochromatosis: clinical and autopsy report of a case","volume":"32","author":"Murakami M.","year":"1969","journal-title":"Nihon Ketsueki Gakkai Zasshi"},{"key":"e_1_2_6_5_1","first-page":"1206","article-title":"Extramedullary hematopoiesis with multiple tumor\u2010simulating mediastinal masses in a patient with beta\u2010thalassemia intermedia","volume":"13","author":"Ben\u2010Bassat I.","year":"1977","journal-title":"Isr. 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