¿Es realmente asintomático el portador de la hemoglobina S? / Is hemoglobin s carrier really asymptomatic?

La controversia sobre si el estado de portador de la hemoglobina S debe ser visto como una enfermedad benigna o como un fenotipo intermedio de la anemia de células falciformes se mantiene hasta nuestros días. Los reportes de complicaciones renales, tromboembólicas y de muerte súbita relacionadas con el ejercicio en estos individuos, demandan la necesidad de un consenso en relación con este concepto. Nuestro objetivo es dirigir la atención hacia este grupo de personas que presentan una afectación genética de la síntesis de hemoglobina, identificar y detectar tempranamente complicaciones derivadas de esta condición genética, con el fin de proporcionarles una mejor atención médica y contribuir a definir si realmente el portador de la hemoglobina S es asintomático(AU)

Controversy over whether sickle cell trait should be considered as a benign disease or as an intermediate phenotype of sickle cell anemia has remained to this day. Reports of renal complications and sudden death associated to exercise in these individuals as well as thromboembolic complications demand the need for consensus regarding this concept. It is our goal with this paper to draw attention to this group of individuals, identifying and detecting early complications of their genetic condition in order to provide better health care and actually help to define whether or not sickle cell trait is asymptomatic in carriers(AU)

Sickle hemoglobin disturbs normal coupling among erythrocyte O2 content, glycolysis, and antioxidant capacity.

Energy metabolism in RBCs is characterized by O2-responsive variations in flux through the Embden Meyerhof pathway (EMP) or the hexose monophosphate pathway (HMP). Therefore, the generation of ATP, NADH, and 2,3-DPG (EMP) or NADPH (HMP) shift with RBC O2 content because of competition between deoxyhemoglobin and key EMP enzymes for binding to the cytoplasmic domain of the Band 3 membrane protein (cdB3). Enzyme inactivation by cdB3 sequestration in oxygenated RBCs favors HMP flux and NADPH generation (maximizing glutathione-based antioxidant systems). We tested the hypothesis that sickle hemoglobin disrupts cdB3-based regulatory protein complex assembly, creating vulnerability to oxidative stress. In RBCs from patients with sickle cell anemia, we demonstrate in the present study constrained HMP flux, NADPH, and glutathione recycling and reduced resilience to oxidative stress manifested by membrane protein oxidation and membrane fragility. Using a novel, inverted membrane-on-bead model, we illustrate abnormal (O2-dependent) association of sickle hemoglobin to RBC membrane that interferes with sequestration/inactivation of the EMP enzyme GAPDH. This finding was confirmed by immunofluorescent imaging during RBC O2 loading/unloading. Moreover, selective inhibition of inappropriately dispersed GAPDH rescues antioxidant capacity. Such disturbance of cdB3-based linkage between O2 gradients and RBC metabolism suggests a novel mechanism by which hypoxia may influence the sickle cell anemia phenotype.