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Although the diagnosis of VOC is usually based on the repetitive history of syncope, it should be remembered that the history is often unreliable. The diagnosis can be confirmed by the electrocardiogram, an echocardiogram, computerized tomography scan, or the confirmation of the start of a hemolytic episode by the observation of the fall of haptoglobin. The diagnosis can be complicated by the false positive results of blood gas tests because of reactions of stored hemoglobin to components of metabolized nitrates in the test, and screening for SCA can be falsely negative if screening is carried out during the acute phase of a VOC. As a result, serial blood examination for the detection of hemolysis and reticulocytes is of great value in the diagnosis of VOC. In the case of a positive blood test, evaluation for the presence of subcutaneous or truncal petechiae and ecchymosis, conjunctival pallor with anisokoria, and renal impairment in the patient that suggest increased endogenous release of free heme is also indicated [48].

The antioxidants melatonin, resveratrol, and serotonin (5-HT) are all involved in the generation of large amounts of free oxygen radicals and thus play a major role in aging. The melanocortina-4 receptors (MC4-Rs) are key in the release of serotonin. 7211a4ac4a