Sickle cell trait diagnosis: clinical and social implications

Abstract

The sickle hemoglobin (HbS) point mutation has independently undergone evolutionary selection at least five times in the world because of its overwhelming malarial protective effects in the heterozygous state. In 1949, homozygous Hb S or sickle cell disease (SCD) became the first inherited condition identified at the molecular level; however, since then, both SCD and heterozygous Hb S, sickle cell trait (SCT), have endured a long and complicated history. Hasty adoption of early mass screening programs for SCD, recent implementation of targeted screening mandates for SCT in athletics, and concerns about stigmatization have evoked considerable controversy regarding research and policy decisions for SCT. Although SCT is a largely protective condition in the context of malaria, clinical sequelae, such as exercise-related injury, renal complications, and venous thromboembolism can occur in affected carriers. The historical background of SCD and SCT has provided lessons about how research should be conducted in the modern era to minimize stigmatization, optimize study conclusions, and inform genetic counseling and policy decisions for SCT.

Figure 1. Timeline of major discoveries in sickle hemoglobin and sickle cell trait screening mandates

DoD indicates Department of Defense; and NCAA, National Collegiate Athletic Association.