Factors contributing to anemia in SCD. The main mechanisms driving anemia in SCD include intravascular and extravascular hemolysis, decreased EPO production, and incomplete bone marrow compensation. Different mechanisms may predominate or act synergistically in different individuals with SCD, contributing to the phenotypic variability of the disease. Using a combination of targeted therapies to address more than 1 mechanism simultaneously may provide more effective and individualized approaches to treating anemia in SCD.