Sickle Cell Disease and the Endothelium

The enduring puzzle of sickle cell anemia is how a single deviant base in DNA, which changes a single amino acid in a single protein within a single type of cell, causes a disease with such variable clinical manifestations. Clearly, additional factors — situational and genetic — influence the course of this genetically simple yet clinically complex disorder. Genetic variables that influence the severity of sickle cell disease include levels of other hemoglobins, such as hemoglobin F or hemoglobin C. Other factors, such as responses to episodes of infectious disease, are strongly suspected to predispose patients to sickle crises, but . . .