Monovalent cation changes in sickle erythrocytes: a direct reflection of alpha-globin gene number

It has been suggested that the less severe anemia that exists in patients with sickle cell anemia who also have alpha-thalassemia is related to an effect on the sickling of erythrocytes. To test this hypothesis, we used as a measure of sickling the change in sickle erythrocyte sodium and potassium content that occurs during deoxygenation. Sickle cells from individuals with four, three, or two alpha-globin genes were deoxygenated, and the change in monovalent cation content measured to determine whether a relationship exists between alpha-globin gene number and sickling. In samples of cells depleted of irreversibly sickled cells, the alpha-globin gene number was directly related to the magnitude of mean cation change and inversely related to the ratio of membrane surface area to cell volume. These data indicate that alpha-thalassemia is associated with a diminished degree of sickling in individuals with sickle cell anemia. They also suggest that excess cell membrane may play a role in this protective effect.