Iron Overload, Chelation Gaps and Marrow Injury in Beta-Thalassemia Major: A Cross-Sectional Study from Khyber Pakhtunkhwa, Pakistan

Abstract

Background: Beta-thalassemia major (BTM) remains the most prevalent hereditary haemoglobinopathy in Pakistan, with an estimated carrier frequency of 5–7%, which translates to several thousand new diagnoses each year, further straining the healthcare system. Repeated transfusions improve their survival rate but inevitably expose them to iron overload that can damage their organs, especially the bone marrow.

Objective: To correlate haematological profiles of BTM patients with their bone marrow histopathological findings and determine predictors from haematological variables for advanced marrow disease. Methods: An analytical cross-sectional study, enrolling 100 consecutive BTM patients at a tertiary referral centre in Khyber Pakhtunkhwa province, i.e., Khyber Teaching Hospital Peshawar, was undertaken (April–October 2024). Complete blood count, reticulocyte count, serum ferritin, and foetal haemoglobin were measured. Trephine biopsies of bone marrow were assessed for cellularity, erythroid hyperplasia, iron stores (Gale grading), and fibrosis (Myelofibrosis grading). Extramedullary haematopoiesis was also recorded through additional imaging. Spearman's rank correlation, chi-square, and Kruskal-Wallis tests were applied. P <0.05 was considered significant. Results: Patients had mean age of 10.52±3.05years (49% males), haemoglobin of 6.26±1.34g/dL, and serum ferritin of 2568±1483 ng/mL. Marked marrow hypercellularity was noticed in 33%, while marked erythroid hyperplasia in 34% of patients. Serum ferritin correlated strongly with Gale grades of iron stores (rₛ = +0.78, p < 0.001) and fibrosis grades (rₛ = +0.71, p < 0.001). Haemoglobin demonstrated inverse correlation with marrow cellularity (rₛ = −0.69, p < 0.001). Patients had significantly less serum ferritin and lower marrow histopathological grades when on deferasirox as compared to no chelation therapy or other alternatives (p <0.001). Conclusion: Serum ferritin and haemoglobin are reliable indicators for marrow disease burden in BTM, where marrow biopsy is not convenient. Inadequate chelation is strongly associated with advanced marrow injury. These findings should be adopted by thalassemia programmes in Pakistan along with uninterrupted chelation access.

Keywords: Beta-thalassemia major; bone marrow histopathology; iron overload; serum ferritin; erythroid hyperplasia; chelation therapy; Pakistan.