Pathophisiology of Sickle Cell Disease Treatment

A homozygous mutation in the gene for (HbA), is the proximate cause of sickle cell disease (SCD). Sickle hemoglobin (HbS) shows peculiar biochemical properties, which lead to polymerizing when deoxygenated. HbS polymerization is associated with a reduc increased red cell density which further accelerate HbS polymerization. Dense, dehydrated erythrocytes are likely to undergo instant polymerization in conditions of mild hypoxia due to their high HbS concentration, and HbS polymers may be formed under normal oxygen pressure. Pathophysiological studies have shown that the dense, dehydrated red cells may play a central role in acute and chronic clinical manifestations of sickle cell disease, in which intravascular sickling in capillaries and small vessels leads to vaso blood flow in a variety of organs and tissue. The persistent membrane damage associated with HbS polymerization also favors the generation of distorted rigid cells a to vaso-occlusive crisis (VOCs) and cell destruction in the peripheral circulation. These damaged, dense sickle red cells also show a loss of phospholipid asymmetry with externalization of phosphatidylserine (PS), which is believed t promoting macrophage recognition with removal of erythrocytes (erythrophagocytosis). Vaso-occlusive events in the microcirculation result from a complex scenario involving the interactions between different cell types, includin reticulocytes, abnormally activated endothelial cells, leukocytes, platelets and plasma factors such as cytokine and oxidized pro currently the only drug approved for disease to prevent acute painful crises and reduce the incidence of transfusion and acute chest crises. Here, we will focus on consolidated and experimental therapeutic strategies for the treatment of sickle cell disease, including: a) agents which reduce or prevent sickle cell dehydration www.mjhid.org ISSN 2035-3006