Mechanisms, Risk Identification, and Prevention of Thrombosis in Sickle Cell Disease and β-Thalassemia: An Updated Narrative Review

Background: Sickle cell disease (SCD) and β-thalassemia are chronic thromboinflammatory disorders associated with venous, arterial, and microvascular thrombotic complications. However, evidence regarding disease-specific risk stratification and thrombosis prevention remains fragmented. This review summarizes current evidence on the mechanisms, risk identification, and prevention of thrombosis in these disorders. Methods: A narrative review of the literature was conducted using PubMed and Scopus to identify studies evaluating the thrombotic mechanisms, risk factors, biomarkers, and preventive strategies in SCD and β-thalassemia. Results: Thrombotic complications arise through interconnected mechanisms involving chronic hemolysis, nitric oxide depletion, endothelial dysfunction, phosphatidylserine exposure, microparticle generation, platelet activation, tissue factor expression, and enhanced thrombin generation. ADAMTS13–von Willebrand factor dysregulation may contribute to platelet adhesion and microvascular thrombosis, whereas NETosis and complement activation remain emerging mechanisms requiring further clinical validation. In SCD, thrombotic risk is associated with factors including pregnancy, recurrent hospitalization, central venous access devices, prior thrombosis, and pulmonary hypertension. In β-thalassemia, higher thrombotic event rates have been reported in non-transfusion-dependent disease, particularly among patients who have undergone splenectomy or have thrombocytosis, severe anemia, nucleated erythrocytosis, or pulmonary hypertension. Although several biomarkers reflect thromboinflammatory activity, none has been prospectively validated for routine risk prediction. Thromboprophylaxis is therefore generally limited to established high-risk clinical settings and is largely extrapolated from general venous thromboembolism guidelines. Observational data suggest that direct oral anticoagulants may be associated with similar rates of VTE recurrence and possibly lower rates of major bleeding than vitamin K antagonists in SCD; however, the certainty of evidence is very low. Conclusions: Current thrombosis management in SCD and β-thalassemia relies primarily on individualized risk assessment and extrapolation from general VTE recommendations. Prospective multicenter studies, randomized trials, and validated disease-specific risk prediction models are needed to optimize thrombosis prevention and anticoagulation strategies in these disorders.