Milder Clinical Course of Sickle Cell Disease in Patients With α Thalassemia in the Indian Subcontinent

To the Editor:

We read with interest the report entitled “Clinical Events in the First Decade in a Cohort of Infants With Sickle Cell Disease” by Gill et al1 and the subsequent correspondence on the same problem by Billett et al.2 We have been studying the natural history and clinical profile of sickle cell disease in western India for several years. One of our interests was to see how the coinheritence of α thalassemia along with homozygous sickle cell disease influences the clinical and hematologic expression of the disease in individuals between 10 to 35 years of age. We studied 42 patients with sickle cell disease confirmed by standard hematologic tests and also by DNA analysis (Ddel polymorphism). These patients underwent a detailed clinical examination and the data were entered with special reference to number of painful crisis, hospital admissions, acute chest syndrome, number of blood transfusions received, and rate of infections per year. DNA samples of these patients were analyzed for α globin genotyping by Southern blot hybridization.3 

Our findings showed that 15 patients with a normal α globin gene complement had 42 episodes of various complications and 11 patients with heterozygous α+ thalassemia (−α/αα) had 12 episodes, whereas 16 patients with homozygous α+ thalassemia (−α/−α) had only 8 episodes of similar complications. These three groups were comparable in age and sex. Thus, our patients show fewer complications with coinheritence with homozygous α+ thalassemia (P < .001), which is statistically significant. When painful crisis was separately analyzed in these three groups, the results were similar, ie, 73% of patients with a normal α globin genotype had painful crisis compared with 18% of the sickle cell disease patients with homozygous α+ thalassemia (P < .001). Higher hemoglobin levels and red blood cell counts with lower mean corpuscular hemoglobin and mean corpuscular volume values were found in sickle cell disease patients having homozygous α+ thalassemia as compared with those having normal α globin genes (P < .05). However, the fetal hemoglobin level was not significantly different in these groups of patients and ranged between 8% and 30%. Splenomegaly was present in significantly higher number in patients with homozygous α+ thalassemia as compared with patients with a normal α globin genotype (60% v 16%).

Thus, the present study differs from those of Gill et al1 and Bailey et al4 in showing significantly less number of vasoocclusive crisis when sickle cell disease interacts with homozygous α+ thalassemia in the Indian population. It is well established that sickle cell disease has a varying severity of clinical presentations in different population groups.5 We agree that other epistatic factors also influence the clinical severity of sickle cell disease. An earlier study6 showed that sickle cell disease in Indians was associated with higher levels of fetal hemoglobin and higher incidence of α thalassemia with a milder clinical course and frequent splenomegaly in children. However, in that study, the impact of α thalassemia on the severity of sickle cell disease was not convincingly demonstrated.