Iron overload and iron overload-related complications across the clinical spectrum of hemoglobin H disease: a real-world multicenter registry study from Thailand

Background Iron overload presents as a major cause of long-term morbidity among thalassemia and is increasingly recognized in patients with hemoglobin (Hb) H disease; however, real-world clinical data defining the burden, complications, and associated factors of iron overload across these patients remain poorly characterized. Understanding these factors is important for optimizing iron surveillance and therapeutic strategies for iron overload in patients with Hb H disease. Methods Based on the multicenter registry of Thai patients with Hb H disease, a total of 1,298 patients, comprising both deletional and non-deletional Hb H, were analyzed. Clinical characteristics, iron overload burden, and iron overload-related complications were evaluated across Hb H subgroups. Multivariable regression was used to identify independent predictors of iron overload and any related complications. Results Among 1,298 patients with a median age of 17.2 years (IQR 10.0–39.8), 726 patients (56%) had deletional, and 572 (44%) had non-deletional Hb H disease. Patients with non-deletional Hb H had significantly lower hemoglobin and a substantially higher transfusion burden than those with deletional Hb H. Approximately 20% of patients across the clinical spectrum had iron overload, with significantly higher ferritin and liver iron concentration (LIC) in non-deletional Hb H. Additionally, overall iron overload-related complications were significantly higher among non-deletional Hb H ( p < 0.05). In multivariable analyses, the factors associated with iron overload included non-deletional genotype, increasing age, and Hb E co-inheritance ( p < 0.01). Discussion Iron overload is a significant complication and not uncommon in Hb H disease, particularly among non-deletional subgroups and older patients. These findings emphasize that transfusion burden alone is insufficient to identify patients at risk of iron overload and underscore the need for comprehensive evaluation across the spectrum of Hb H disease, even among non-transfusion-dependent thalassemia (NTDT). To our knowledge, this study represents one of the largest multicenter real-world evaluations of iron overload and its clinical consequences specifically in Hb H disease.