Beyond the blood: A practical guide to thalassemia care in the emergency department

β-thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic anemia, and iron overload. Improved survival rates due to advances in transfusion and iron chelation therapies have shifted the clinical burden toward managing complex, often acute, complications that commonly present to the emergency department (ED). This review provides an evidence-based, system-oriented framework for emergency physicians to recognize and manage β-thalassemia-related emergencies. Initial ED assessment should focus on hemodynamic stability, transfusion history, iron chelation regimen, and complications such as splenectomy or infections. Common presentations include symptomatic anemia, cardiac decompensation, thromboembolic events, infections, and transfusion-related reactions. Cardiac complications, ranging from arrhythmias to iron-overload cardiomyopathy, are the leading cause of mortality and require urgent intervention. Pulmonary hypertension, high-output heart failure, and thromboembolic events are prevalent, particularly in non-transfusion dependent and splenectomized patients. Infectious complications, especially in asplenic individuals, can progress rapidly and warrant early empiric antibiotic therapy. Neurological presentations such as spinal cord compression or stroke may be under-recognized but necessitate immediate imaging and multidisciplinary care. Renal dysfunction, leg ulcers, cholelithiasis, and endocrinopathies further complicate emergency presentations. Effective ED management relies on prompt recognition, appropriate diagnostics, and early consultation with hematology, cardiology, infectious disease, and surgical teams. Incorporating transfusion protocols, chelation adjustments, and disposition planning enhances continuity of care. By increasing awareness and training, ED providers can significantly impact outcomes in this growing patient population. This review aims to bridge the knowledge gap and provide practical guidance for acute care providers encountering β-thalassemia-related emergencies.