Pathobiology of Sickle Cell Disease

Since it was recognized as the “first molecular disease,” sickle cell anemia caused by homozygosity for the mutant sickle beta-globin gene has provided the classic paradigm for single-gene disorders. Predominant clinical features include hemolytic anemia, episodic painful vasoocclusive events, an inflammatory vasculopathy, chronic organ deterioration, and a foreshortened life span. The genesis of clinical sickle cell anemia is complicated, and an understanding of its pathophysiology integrates concepts from multiple scientific disciplines, includes contributions from the red blood cell (RBC) membrane and the vascular wall endothelium, and recognizes the likely participation of multiple genetic influences. This chapter addresses the fundamental pathophysiology that underlies the sickle cell disease syndromes described in Chapter 43.