The interplay of sleep disordered breathing, nocturnal hypoxemia, and endothelial dysfunction in sickle cell disease

Background: Sickle cell disease (SCD) is a genetic hemoglobinopathy with an incidence of 250-300,000 births per year worldwide. SCD leads to a diffuse vasculopathy which underlies a broad range of clinical complications which can be fatal. Obstructive sleep apnea (OSA) and nocturnal hypoxemia are more frequent in sickle cell disease than in the general population. The impact of OSA and hypoxemia on endothelial dysfunction and clinical outcomes has not been fully characterized. Aim of review: We reviewed available data regarding the prevalence of OSA and nocturnal hypoxemia and their associations with clinical outcomes and endothelial dysfunction in SCD. Key scientific concepts of review: Sleep disordered breathing (SDB) encompasses a spectrum of disorders of oxygenation and ventilation during sleep. Intermittent hypoxemia, including nocturnal hypoxemia, impacts the health of the endothelium and contributes to acute and chronic complications of SCD, most notably, cerebrovascular and cognitive defects. Specific treatment for SDB can be effective at helping to prevent some of these complications, in conjunction with SCD-targeted therapy. Hydroxyurea is the only therapy that has been studied in this context, however, newer agents may also provide benefit.