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Although this disease begins with the polymerization of red blood cells during its deoxygenating phase, it can erupt into a cascade of debilitating conditions such as ischemia\u2010reperfusion injury, inflammation, and painful vaso\u2010occlusion crises. The purpose of this review is to discuss how these phenomena can result in the formation of oxidative stress as well as limit nitric oxide (NO) bioavailability and decrease antioxidant status. The cumulative effects of these traits cause an increase in other forms of reactive oxygen species (ROS), which in turn intensify the symptoms of SCD and generate a vicious circle. 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