NO reacts with oxygenated Hb and reduced Hb to produce nitrate plus met-Hb and iron-nitrosyl-Hb, respectively; NO has several mechanisms of action, but it appears to play a major role in both the regulation of vascular muscle tone at the cellular level as well as in platelet aggregation (clumping).49 In SCD, especially in SCA disease, the rapid release of cell-free Hb may exceed the normal clearance mechanisms such as by binding to haptoglobin, and thus the excess free Hb consumes NO and impairs its regulatory role.5 This evidence concerns the gene GSTM1 and Schnyder corneal dystrophy.