SICKLE CELL DISEASE: APPROACH IN INFLAMMATORY TARGETS BY HYDROXYUREA

Abstract

Introduction: Sickle cell disease is a disorder of the beta-globin monogenic characterized by abnormal production of hemoglobin structure (Hb) variant S. This change causes severe hemolytic anemia and pain episodes because of vaso-occlusive crisis leading to a deficiency in oxygen supply to the tissues with consequent organ damage. For several decades it has become clear that a more complex process contributes to the myriad of disease, since the clinical complications caused by inflammation were observed clinically in patients. Inflammation is a critical component in the pathophysiology of sickle cell anemia as it impacts on many system pathways, thereby inflammation occurs by several factors such as the extracellular heme, the inflammassome, nuclear factor kappa B (NF-kB), mast cells, inflammatory pathways invariant lymphocytes, natural killer T cell, among others. Hydroxyurea is the only drug approved by the Food and Drug Administration for sickle cell anemia, this drug reduces many clinical events such as pain episodes by vaso-occlusion, hospitalization, acute pulmonary syndrome and transfusion requirements. Objective: The objective of this study was to survey about sickle cell anemia focusing on some inflammatory targets by hydroxyurea. Methodology: For this review we use scientific books and articles on the subject, the latter being accessed through Scielo and Pubmed, and using the following keywords: sickle cell anemia, hemoglobin variant S, inflammation pathways, hydroxyurea, and pathogenesis of sickle cell disease. Conclusion: We conclude that hydroxyurea reacts with deoxy-Hb, oxy-Hb and Met-Hb generating nitrol-Hb. Thus the anti-inflammatory effect is to reduce tumor necrosis factor-alpha and increase interleukin-10 which is an inhibitor of activated macrophages, which reduces episodes of pain by vessel occlusion and acute chest syndrome.