Beyond Hemoglobinopathies: Non-Hemoglobinopathy Causes of Transfusion-Dependent Anemia in Children.

Transfusion-dependent anemia (TDA) in children is often attributed to hemoglobinopathies; however, a spectrum of non-hemoglobinopathy disorders can also lead to transfusion dependence, complicating diagnosis and management. In this article, we share our experience with such non-hemoglobinopathy causes of TDA. A retrospective chart review was conducted over five years (2018-2023) at a tertiary pediatric hematology center. Among 93 children identified with TDA, 80 had hemoglobinopathies, while 13 had alternative diagnoses. These included immune-mediated hematological disorders, marrow failure syndromes, congenital RBC/platelet defects, and systemic illnesses. Descriptive statistics summarized clinical and demographic data. Of the 93 children with TDA, 13 had non-hemoglobinopathy causes: immune-mediated disorders (AIHA, Evans syndrome, PRCA, n = 4), marrow failure syndromes (sideroblastic anemia, dyskeratosis congenita, n = 3), inherited red cell/platelet defects (G6PD deficiency, Glanzmann thrombasthenia, n = 3), and systemic illnesses (vasculitis, Langerhans cell histiocytosis, hypereosinophilic syndrome, n = 3). The mean age was 4 years 5 months, with a male-to-female ratio of 1.16:1. Hepatosplenomegaly was observed in 8/13 cases. Non-hemoglobinopathy causes of TDA are heterogeneous, encompassing systemic, immune, genetic, and marrow failure disorders. Structured diagnostic evaluation is critical to distinguish them from hemoglobinopathies, enabling accurate treatment and improved outcomes.