Sickle Cell Disease: From bench to bedside to prevention

Sickle cell disease describes a group of disorders characterized by mutations in the beta-globin gene, including homozygous (Hb SS) and compound heterozygous conditions (Hb-S beta O Thalassemia, Hb S-C, and others) with distinctive clinical manifestations. Pathophysiologically, SCD is caused by a single point mutation at colon 6 of the beta-globin gene that results in a valine to glutamine substitution. Sickle cell trait is present in 1 out of 600 Africa-Americans with over 70,000 Americans with SCD. Each year 1,000 infants are born with SCD. In the decades since 1968, mortality rates for children with SCD have decreased markedly due to early diagnosis with newborn screening, the introduction of prophylactic penicillin for newborns and pneumococcal and other immunizations. Major causes of death: sepsis, stroke, splenic sequestration, pulmonary emboli, renal and hepatic failure and massive hemolysis. Sudden, unexpected death and pulmonary hypertension are becoming more common as the population of patients has aged.

Multidisciplinary care has improved the health status of children. Other advancements in care include the use of prophylactic transfusion for stroke prevention, improvement in vaccination rates, the use of hydroxyurea to increase fetal hemoglobin concentration and in a limited number of cases, hematopoietic (blood and marrow) stem cell transplantation. Both acute and prophylactic transfusion therapy is being advocated for increasingly more complications. Transfusion complications have increased in frequency and include RBC allo and autoantibody development and iron overload, each with their own diagnostic and therapeutic complications.