Hemostatic Imbalance in Thalassemia: From Molecular Mechanisms to Clinical Manifestations

Abstract

Thalassemia is a hereditary hemoglobinopathy characterized by defective globin chain synthesis, leading to chronic anemia and systemic complications. Among these, hemostatic imbalance has gained increasing attention due to its contribution to significant morbidity and mortality. This review explores the complex molecular mechanisms underpinning coagulation disturbances in thalassemia, including chronic hemolysis-induced endothelial dysfunction, platelet activation, microparticle generation, and coagulation factor alterations. These pathophysiological changes foster a prothrombotic state while occasionally predisposing to bleeding complications. Clinically, patients with thalassemia exhibit a broad spectrum of hemostatic manifestations ranging from thromboembolic events such as deep vein thrombosis and stroke to bleeding tendencies associated with platelet dysfunction and coagulopathy. Diagnostic evaluation is complicated by overlapping clinical features and the limitations of routine coagulation assays, necessitating more advanced testing modalities to accurately assess coagulation status and guide management. The impact of factors such as splenectomy, iron overload, and oxidative stress on hemostasis further complicates clinical care. Effective management of hemostatic imbalance in thalassemia requires a multidisciplinary approach that balances thrombotic and bleeding risks. Current strategies include anticoagulation, iron chelation, and careful monitoring of coagulation parameters. Advances in molecular diagnostics and emerging targeted therapies offer promising avenues for personalized care. This review underscores the importance of understanding hemostatic alterations in thalassemia to improve clinical outcomes and highlights areas for future research.