The Interaction of Alpha-Thalassemia and Homozygous Sickle-Cell Disease

TLDR

Sickle‑cell disease patients can also carry alpha‑thalassemia 2, either homozygous, heterozygous, or normal, affecting their alpha‑globin gene complement. The study compared clinical and hematologic features of 44 sickle‑cell patients with homozygous alpha‑thalassemia 2 to controls with the two hematologic conditions. Homozygous alpha‑thalassemia 2 in sickle‑cell patients was associated with higher red‑cell counts, hemoglobin, and HbA2, lower HbF, MCH, MCHC, MCV, reticulocytes, irreversibly sickled cells, and bilirubin, fewer acute chest syndrome and leg ulcers, more splenomegaly, confirming that alpha‑thalassemia mitigates sickling and reduces hematologic severity.

Abstract

Patients with homozygous sickle-cell disease may be homozygous for alpha-thalassemia 2 (alpha-/alpha-), may be heterozygous for alpha-thalassemia 2 (alpha-/alpha alpha), or may have a normal alpha-globin-gene complement (alpha alpha/alpha alpha). We compared the clinical and hematologic features of 44 patients who had sickle-cell disease and homozygous alpha-thalassemia 2 with those of controls with the two hematologic conditions. The patients with homozygous alpha-thalassemia 2 had significantly higher red-cell counts and levels of hemoglobin and hemoglobin A2, as well as significantly lower hemoglobin F, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, reticulocyte counts, irreversibly-sickled cell counts, and serum total bilirubin levels, than those with a normal alpha-globin-gene complement. Heterozygotes (alpha-/alpha alpha) had intermediate values. In the group with homozygous alpha-thalassemia 2, fewer patients had episodes of acute chest syndrome and chronic leg ulceration and more patients had splenomegaly, as compared with patients in other two subgroups. These data confirm previous suggestions that alpha-thalassemia inhibits in vivo sickling in homozygous sickle-cell disease and may be an important genetic determinant of its hematologic severity.