Sickle cell anemia, thalassemia, and congenital hemolytic anemias

Each year, an estimated 300,000 infants are born with either of the two most common hemoglobinopathies: the sickle cell diseases or the thalassemias. These inherited diseases are the most prevalent monogenetic disorders worldwide. Sickle cell disease makes up 85% of the total infants, and thalassemias the remaining 15%. It is increasingly apparent that sickle cell disease and thalassemia have become a major health challenge in emerging countries as more infants with hemoglobinopathies survive beyond infancy and into adulthood. The prevalence of significant hemoglobin trait (Hb S, Hb C, Hb E, Hb D, etc., and β thalassemia and α thalassemia) varies from about 1% in all of Europe to as high as 18% in all of Africa; the prevalence in the American population is 3%. The presence of disease is 10.8/1000 in Africans, 0.6/1000 in Americans, and 0.2/ 1000 in all of Europe. Half of the people in the world with sickle cell disease live in three countries: Nigeria, Democratic Republic of Congo, and India. InWest Africa, about 1,000 infants a day are born with sickle cell disease. In the world’s population, 1.5% are β thalassemia mutation carriers. Hemoglobin E–beta thalassemia (Hb E/β thalassemia) is the genotype responsible for approximately one-half of all severe β thalassemia worldwide. The distributions of the phenotype and genotype of North American thalassemia patients today—as well as their transfusion management—are dramatically different from those in the past decades. The majority of patients, previously of Mediterranean descent, are now largely of Asian, Indian, and Middle Eastern origin. In Thailand, about 3,000 affected children are born annually, with estimates of about 100,000 living patients. In southern China, the gene frequencies for β-thalassemia and for Hb E are over 4%, resulting in thousands of annual births of β thalassemia major and hemoglobin Hb E/β thalassemia. Due to the diaspora occurring in the past and present, sickle cell disease and thalassemia can now be found in areas that are free of malaria. Sickle hemoglobin is a structural variant causing severe disease in the homozygous state and when in combination with other hemoglobin variants. The α and β thalassemias are genetically diverse with more than 200 mutations accounting for decreased production of hemoglobin in those affected. The thalassemia phenotype varies from mild to severe states of anemia. The heterozygote is mildly protective against malaria with increased prevalence in some areas of the world. Red cell transfusions are indicated for both of these hemoglobinopathies. In sickle cell disease, transfusions prevent and/or treat complications and ameliorate anemia. In the thalassemias, transfusion prevents the anemia associated with decreased or absent hemoglobin production.