Clotting, inflammation, and immunity: the multifaceted role of platelets in HIV and sickle cell disease - a narrative review.

Platelets, long recognized for their function in hemostasis, are increasingly acknowledged for their role in immune modulation and inflammation, especially regarding complex co-infections. This review examines the complex role of platelets in co-infection with HIV and sickle cell disease (SCD), highlighting their functions that go beyond coagulation and contribute to chronic inflammation, immune activation, and vascular dysfunction. In HIV, there is an increase in platelet activation, fostering inflammation and endothelial dysfunction, thereby raising the likelihood of thrombotic events. Likewise, in SCD, platelets play a role in vaso-occlusion, which worsens the microvascular issues associated with the disease. The overlap of HIV and SCD complicates platelet function, enhancing both pro-coagulant and pro-inflammatory pathways. In SCD, platelet aggregation speeds up endothelial damage, and immune activation from HIV worsens this condition, increasing the chances of thromboembolic incidents. Platelets engage with immune cells, enhancing T cell activation and HIV viral replication, while creating an inflammatory environment that exacerbates the pathology of both conditions. These interactions establish a detrimental cycle of platelet dysfunction, inflammation, and tissue injury, which presents considerable difficulties for patient care.