The interaction of coexistent alpha-thalassemia and sickle cell anemia: a model for the clinical and cellular results of diminished polymerization?

Abstract

Review of the studies on the interaction of alpha-thalassemia and sickle cell anemia reveals a consistently beneficial effect on the severity of anemia and the rheologic and cellular properties of sickle cells. The predominantly vaso-occlusive clinical aspects of sickle cell anemia studied are not uniformly benefited by the presence of alpha-thalassemia. These variable results may be related to the detrimental effects of higher hematocrit on whole blood viscosity. The effects of alpha-thalassemia on sickle cell anemia are probably related to a fundamental effect on MCHC and polymerization, although coexistent effects on other properties of sickle cells and the possibility that the MCHC differences may be secondary to sickling effects cannot be excluded. In total, alpha-thalassemia is an imperfect model for the effects of polymerization on the clinical consequences of sickle cell disease. An important inference from the published literature is that the severity of anemia may be a more important determinant of the ultimate clinical consequence of sickle cell anemia, life expectancy, than has previously been appreciated. Although the effect of alpha-thalassemia is an imperfect model for modified polymerization, studies of the phenotypic result of the interaction of these two genotypes will provide further insight into the causes of clinical diversity in sickle cell disease.