Red Blood Cell Extracellular Vesicles as Key Players in Thromboinflammation.

Thromboinflammation is an emerging concept which highlights the interactions between coagulation and inflammation in various disease states. Activation of coagulation and inflammation are both hallmarks of hemolytic states. However, the mechanisms by which they cause adverse outcomes in hemolytic disorders is incompletely understood. A body of literature suggests that red blood cells (RBCs) play a role in thrombosis and in immune regulation. RBCs release extracellular vesicles (RBC-EVs), with increased numbers found in the circulation of patients with hemolytic disorders. In this review, we summarize the existing literature addressing the interaction of RBC-EVs with coagulation and inflammatory pathways in vitro and in vivo. Additionally, we discuss the potential contribution of RBC-EV-induced thromboinflammation in the pathogenesis of certain complications of sickle cell disease as a model of a severe hemolytic disorder.