Perspective Chapter: Fetal Hemoglobin Modulators

Fetal hemoglobin (HbF) is a dominant hemoglobin of fetal life, which persists until the first six months of the postnatal period. The transition from fetal to adult hemoglobin is regulated through a transcriptional switch within erythroid precursors. HbF plays a vital role in the oxygen transport and possesses a high affinity for oxygen. The presence of deoxy HbS and its intracellular polymerization forms the baasis of disease pathophysiology. Of the several parameters that influences rate and extent of polymerization, fetal hemoglobin iplays a vital role that affects intracellular HbS polymerization. Hence fetal hemoglobin is of greatsignificance in the pathophysiology of sickle cell anemia, where it ranges from 2% to 20% and is influenced by several factors. The higher HbF percentage in patients with sickle cell disease is associated with a reduced risk of morbid clinical events and decreases the overall morbidity. Therefore, evaluation of HbF is of great significance and also the principal target in sickle cell disease management. The possibility of therapeutic induction of HbF remains the most direct and effective methodology to mitigate the pathophysiology of sickle cell disease. Several modulators of Hb F are studied and some under reserach so as to understand which one acts best and effective in a patient. Though the traditional pharmacological approaches have set a bench mark, the treatment landscape is rapidly evolving in patients of sickle cell anemia. This chapter highlights and briefley discusses the current knowledge about such modulators, their therapeutic action on fetal hemoglobin and effectiveness in sickle cell anaemia.