Alloimmunization in sickle cell disease: Addressing an ongoing clinical challenge

Transfusion therapy remains a cornerstone in the management of sickle cell disease (SCD). Yet, repeated exposure to donor red blood cells poses a substantial risk for alloimmunization against red blood cell antigens. Patients with SCD exhibit a disproportionately high incidence of alloimmunization and often experience more severe clinical consequences than other transfusion-dependent populations. This review explores the multifactorial mechanisms underlying this heightened immunogenicity, the clinical and immunologic sequelae that result, and the factors contributing to the under-recognition of alloimmunization's impact in SCD. It will also highlight current and emerging strategies to prevent alloimmunization and advances in the management of its complications, including delayed hemolytic transfusion reactions.