Schematic representation of sources of intravascular ROS in SCD pathophysiology. Mitochondria retention along with other causative factors in RBCs and reticulocytes can oxidize the membrane proteins and lipids, leading to intravascular hemolysis. Hemolytic products released to the vascular lumen further generate highly reactive ROS and create a cycle in SCD. Hemolytic products, including cell-free hemoglobin (1), arginase (2), free iron (3), and lactate dehydrogenase, are released into plasma, and increased activities of XO and NADPH (4) cause ROS mediated endothelial cell damage. These products activate PMNs (5), platelets, and monocytes (6), which further increase endothelial cell damage.