Methemoglobinemia and ascorbate deficiency in hemoglobin E β thalassemia: metabolic and clinical implications

Abstract

During investigations of the phenotypic diversity of hemoglobin (Hb) E ␤ thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE ␤ thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population.There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective. (Blood. 2012;120(15):2939-2944)

Methemoglobin measure in adult patients with sickle-cell anemia: influence of hydroxyurea therapy

“…It has been shown that hemoglobin has an increased susceptibility to undergo oxidation, and when it is subjected to low oxygen tensions, transforming discoid erythrocytes into sickle erythrocytes, increasing the production of MetHb, hemicromos, or products of heme; and causing globin S precipitation in oxidized form of Heinz bodies (13,15,19) . Naoum e Souza (15) , Allen et al (1) and Silva Filho (19) also observed an increase of MetHb in patients with hemoglobinopathies.…”

Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children

“…[43][44][45] Additionally, methemoglobin, an endothelial cell activator, is increased in thalassemia 42,46 and may be further increased in Hp2-2 individuals following hemolysis BLOOD, 27 MARCH 2014 x VOLUME 123, NUMBER 13 Hp AND SEVERE MALARIA 2013…”

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

“…Haptoglobin and hemopexin are indicated in this figure as general plasma proteins that (respectively) bind free Hb and heme. Under chronic and large-scale hemolysis, these proteins become limited in their ability to quench these free species that intrinsically are highly reactive and cause oxidative damage when circulating freely in plasma (for recent reviews, see 4,48) Notably, haptoglobin levels are significantly reduced in HbE/b-thal patients (5). To the best of our knowledge, hemopexin levels have not been reported for HbE/b-thal.…”