Delayed Recognition and Significant Morbidity in Adults with Non-Transfusion-Dependent Thalassemia

Non-transfusion-dependent thalassemia (NTDT) is characterized by variable degrees of anemia, ineffective erythropoiesis, and iron overload, with a heightened risk of age-related complications. However, the clinical profiles of patients who first present to thalassemia care in adulthood, as well as the gaps in management, are poorly described. In a multi-institutional study, we identified 82 patients with NTDT aged ≥18 years who were referred to three U.S. thalassemia centers between 2013 and 2023. Data were collected by manual chart review and included clinical history, laboratory tests, and imaging. The median age at initial visit was 36.8 years (range 18-74), and 37 (45%) of the patients had α-thalassemia, while 45 (55%) had β-thalassemia. Complications assessed included symptomatic anemia, prior splenectomy, extramedullary hematopoiesis, iron overload, pulmonary hypertension, cardiac arrhythmia, endocrine complications, and thrombosis. Iron overload was common, with 71% of available liver MRIs showing hepatic iron >5 mg Fe/g dry weight. Among patients with LIC >5 mg Fe/g, only 24.4% were on chelation at referral. Strikingly, 49% of patients were recommended to start regular transfusions following the consultation, predominantly for symptomatic anemia or complications of ineffective erythropoiesis. Patients with NTDT referred for initial comprehensive thalassemia care in adulthood had high rates of morbidities and undertreated iron overload. The criteria for initiating regular transfusions must be widely implemented to mitigate long-term complications and improve the quality of life of adults with NTDT.