Haptoglobin: an emerging candidate for phenotypic modulation of sickle cell anemia?☆

ickle cell anemia (SCA) is characterized by a single homozyous mutation (A→T) in the sixth codon of the -globin gene hat results in hemoglobin S (Hb S), in which a glutamic cid residue is substituted by valine in the sixth position f the -globin chain (HBB; glu(E)6val(A); GAG-GTG; rs334).1 his change leads to a wide variety of symptoms, including hronic intravascular hemolysis, increased cell-free plasma emoglobin (Hb) and heme levels and vascular alterations.2 CA has been characterized as a chronic inflammatory state ith abnormal endothelial activation as a result of various ssociated factors. The mechanisms that induce the prouction of inflammatory mediators and the effects of these olecules on the inflammatory response are little understood n this disease.3 Sickled red blood cells are stiff and therefore have a predisosition to hemolysis; one third of the cells are destroyed in he intravascular space leading to increased cell-free plasma b and heme levels.4 The pathophysiological effects associted with free Hb/heme are acute hemodynamic instability nd acute or chronic vascular injury.5 The toxicity and inflamatory nature of free Hb are a result of the greater nitric oxide onsumption it promotes and the consequent accumulation f hydroxyl radicals and reactive oxygen species in the blood essels. The organism’s first defense mechanism against the armful effects of free Hb involves haptoglobin (Hp), whose rimary function is to bind to free Hb in the plasma, thereby reventing the excretion of iron by the kidneys and protec6,7 ing blood vessels from its oxidative effects. In addition to eing an antioxidant, Hp is a positive acute-phase glycoproein present in plasma with immunomodulatory properties.6,7