Abstract

Transfusion-dependent thalassemia (TDT) is characterized by chronic hemolysis, ineffective erythropoiesis, and iron overload, resulting in persistent oxidative stress and systemic inflammation. Patients with TDT are also at increased risk of thromboembolic complications, suggesting disturbance of hemostatic and immune-related pathways. However, the molecular links between hemolysis, complement-associated pathways, and coagulation abnormalities remain incompletely defined. In this study, quantitative serum proteomics was used to identify differentially expressed proteins in patients with TDT compared with healthy controls. Pathway enrichment and network analyses demonstrated coordinated alterations in proteins associated with complement regulation, coagulation pathways, lipid transport, and regulatory mechanisms. Complement component C3 and prothrombin showed increased abundance, whereas several regulatory and heme-scavenging proteins, including alpha-2-macroglobulin, hemopexin, and ceruloplasmin, were reduced in TDT patients. Selected proteins were further evaluated using ELISA validation, which supported the direction of the proteomic findings. Overall, these results identify a serum proteomic profile consistent with perturbation of complement and coagulation-related pathways in TDT in the context of chronic hemolysis and oxidative stress. This system-level view provides additional insight into thromboinflammatory mechanisms in TDT and supports further investigation of these pathways as potential biomarkers of disease severity.