Overview
Sickle cell disease encompasses hemoglobin genotypes that include at least one HbS allele paired with another beta-globin variant (classically HbSS, HbSC, HbS/beta-thalassemia, and rarer compound heterozygotes). The prototypical HbSS form is the most common and generally most severe.
The central pathophysiologic events are intravascular hemolysis, microvascular vaso-occlusion, and a pro-inflammatory, pro-thrombotic vascular phenotype. Acute vaso-occlusive episodes (VOEs) cause severe pain; chronic complications include stroke, acute chest syndrome, avascular necrosis, nephropathy, retinopathy, and pulmonary hypertension.