PREVALENCE OF COMPLICATIONS WITH ASSOCIATION OF INCREASED SERUM FERRITIN LEVEL IN THALASSEMIA PATIENTS. NEEDS TO BE MORE FOCUSED

Abstract

 β-thalassemia major is a severe hereditary hemoglobinopathy while transfusion therapy is vital for patient survival, it leads to progressive iron accumulation. Elevated ferritin levels have been implicated in a spectrum of life-threatening complications including hepatic dysfunction, cardiomyopathy, endocrine abnormalities, and growth impairment. Despite its clinical significance, the precise correlation between serum ferritin and organ-specific morbidity remains underexplored in resource-constrained settings like Pakistan. Aims and Objectives: To determine the prevalence of major systemic complications among transfusion-dependent β-thalassemia major patients and to evaluate the association between elevated serum ferritin levels and the risk of hepatic, cardiac, endocrine, and growth-related dysfunctions.

Methodology: A multicenter, cross-sectional analytical study was conducted between January and December 2024 at three tertiary care hospitals and thalassemia centers in Lahore, Pakistan. A total of 251 patients aged 4 to 25 years with molecularly confirmed β-thalassemia major receiving regular transfusions were enrolled. Data collection included clinical histories, physical examinations, laboratory investigations, and echocardiography. Serum ferritin levels were measured using electrochemiluminescence immunoassay (ECLIA). Complications were categorized as hepatic (elevated ALT/AST), cardiac (left ventricular dysfunction via echocardiography), endocrine (hypothyroidism, diabetes mellitus), and growth-related (short stature, delayed puberty). Statistical analysis was performed using SPSS v26.0, with t-tests, ANOVA, Pearson correlation, and logistic regression applied to identify associations between ferritin levels and complication risks. Results and Findings: The mean age of participants was 8.3 ± 2.2 years, with a male-to-female ratio of 1.1:1. The average duration of transfusion dependency was 6.7 ± 2.1 years. Chelation compliance was reported in 74% of patients. The mean serum ferritin concentration was 3280 ± 870 ng/mL. Based on ferritin levels, 59.7% of patients exhibited severe iron overload (≥3000 ng/mL), 28.7% moderate (1000–2999 ng/mL), and 11.6% mild (<1000 ng/mL). The prevalence of complications was as follows: hepatic dysfunction in 61.2%, cardiomyopathy in 29.1%, hypothyroidism in 23.1%, diabetes mellitus in 16.7%, and growth retardation in 42.8% of cases. Serum ferritin ≥3000 ng/mL was significantly associated with multi-organ complications (OR = 3.72, 95% CI: 1.98–6.94, p < 0.001). Strong positive correlations were observed between ferritin levels and hepatic dysfunction (r = 0.59, p < 0.001) and moderate correlations with left ventricular dysfunction (r = 0.42, p = 0.003). ANOVA demonstrated significant differences in ferritin means across patients with no, single, and multiple complications (p < 0.001).

Conclusion: Iron overload-related complications are highly prevalent in β-thalassemia major patients, with elevated serum ferritin serving as a strong predictor of systemic morbidity. Serum ferritin levels ≥3000 ng/mL significantly increase the likelihood of hepatic, cardiac, and endocrine involvement. These findings highlight the need for routine ferritin-based risk stratification and early intervention via aggressive chelation protocols to mitigate long-term complications and improve survival outcomes, particularly in low-resource settings.