Association of G6PD ^{−202/−376} with Lower Hemoglobin Concentration but Not Increased Hemolysis in Patients with Sickle Cell Anemia.

What determines the degree of hemolysis and of anemia in patients with hemoglobin SS is not fully known. The rate of hemolysis and severity of anemia are ameliorated by the presence of alpha thalassemia and by higher hemoglobin F percentage. Mild G6PD deficiency in the form of G6PD^-202/-376 may be associated with episodic hemolysis in individuals of African descent, but past studies indicated little influence of G6PD^-202/-376 on the degree of hemolysis and anemia in sickle cell disease patients (1,2). In this study we examined the roles of single and double α-globin deletions and G6PD^-202/-376 on the degree of hemolysis and the hemoglobin concentration in hemoglobin SS patients.

Two hundred sixty two children and adolescents with hemoglobin SS were recruited at three tertiary medical centers and studied at steady state. Principal component analysis was used to develop a hemolytic component from concentrations of lactate dehydrogenase, aspartate aminotransferase and bilirubin. PCR was used to determine the presence of α-thalassemia and G6PD^-202/-376. Multivariate models were employed to determine the independent effects of these genotypes on hemoglobin concentration and degree of hemolysis.

Single a-globin deletion was associated with an estimated 0.4 g/dL increase in steady-state hemoglobin concentration and double α-globin gene deletion with a 0.8 g/dL increase (P = 0.005 for trend) due to, progressively lower degrees of hemolysis (P = 0.004). G6PD^-202/-376 was associated with an estimated 0.7 g/dL decrease in the hemoglobin concentration (P = 0.003) (Figure 1a), but this observation could not be explained by increased hemolysis. Rather, the reticulocyte count was an estimated 22% lower with G6PD^-202/-376 (P = 0.032) (Figure 1b).

G6PD^-202/-376 may be associated with lower hemoglobin concentration in sickle cell anemia and the mechanism is probably impaired erythropoiesis rather than hemolysis. A recent study (3) indicates that G6PD is needed for definitive erythropoiesis as well as for normal survival of red blood cells in the periphery. Our present findings raise the possibility that, in the setting of the markedly increased erythropoiesis of sickle cell anemia, G6PD^-202/-376 may result in impairment in erythropoiesis that is discernible in the peripheral blood hemoglobin concentration.

Figure 1

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Adjusted mean (+ standard error) values. 1a. Hemoglobin adjusted for hemolysis, blood transfusion, white blood cell count. 1b. Reticulocyte count adjusted for hemoglobin and erythropoietin concentrations.

Figure 1

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Adjusted mean (+ standard error) values. 1a. Hemoglobin adjusted for hemolysis, blood transfusion, white blood cell count. 1b. Reticulocyte count adjusted for hemoglobin and erythropoietin concentrations.

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No relevant conflicts of interest to declare.