Natural history and determinants of clinical severity of sickle cell disease

Abstract

Some of the factors determining the extremely variable clinical course of homozygous sickle cell disease are being identified. Genetic factors include α-thalassemia, β-globin gene haplotypes, heterocellular hereditary persistence of fetal hemoglobin, and high total hemoglobin. Other factors include a variety of environmental variables and socioeconomic status. These risk factors, when occurring in conjunction with apparently random precipitating events, produce features of the disease. Many complications—which are age specific, with highest morbidity and mortality in the first 5 years—may be prevented by specific education and prophylaxis. Current median survival in individuals with sickle cell disease in the United States is approximately 40 to 50 years, at which age the major determinants of mortality are chronic end organ damage of the lungs and kidneys.