Abstract
Thrombosis is a significant, yet often under-recognized, complication in individuals with co-infection of sickle cell disease (SCD) and human immunodeficiency virus (HIV). Both diseases independently elevate thrombotic risk, but their combined presence creates a complex pathophysiological environment that exacerbates endothelial dysfunction, inflammation, and procoagulant states. In SCD, sickled red blood cells cause vaso-occlusion and endothelial injury, while HIV contributes to chronic immune activation, dysregulated hemostasis, and increased thrombotic potential. The dual burden of these conditions not only increases the incidence of thrombotic events such as deep vein thrombosis, pulmonary embolism, and stroke, but also complicates their management due to overlapping symptoms and treatment challenges. This review explores the underlying mechanisms that contribute to the heightened risk of thrombosis in patients with both SCD and HIV, focusing on the interaction between these conditions at the molecular, cellular, and systemic levels. The impact of HIV on vascular health, in conjunction with the pathological effects of SCD on blood flow and clotting, creates a synergistic thrombotic risk. Furthermore, the review examines the clinical manifestations, diagnostic challenges, and treatment strategies for managing thrombosis in this co-infected population. Given the potential for significant morbidity and mortality, timely and effective management of thrombotic complications is critical.