The paradox of HbSC disease-Not so benign after all

With the growing interest in precision medicine and personalized treatments for sickle cell disease (SCD) comes a realization that our approach to individuals living with the hemoglobin SC (HbSC) genotype is inadequate. For many decades HbSC was viewed as a milder form of SCD that does not demand aggressive management. Consequently, when resources, funding, and treatments for SCD were limited, clinical and research efforts were largely directed towards the more prevalent homozygous HbSS genotype. This has left many individuals with HbSC disease facing substantial morbidity and limited therapeutic options. Recent evidence demonstrating the efficacy of hydroxyurea in HbSC disease together with the development of a novel murine model, has renewed interest in this understudied genotype. This review highlights the main similarities and differences between HbSS and HbSC disease, addresses common misconceptions regarding HbSC disease, and discusses emerging biomarkers and therapeutic strategies for this patient population.