New insights into the pathophysiology and novel therapies for sickle cell disease

Abstract

Sickle-cell disease is an inherited and multisystem blood disorder characterized by hemolytic anemia with chronic complications punctuated by acute vaso-occlusive crises (VOCs), progressive multiorgan damage, and increased mortality. SCD is one of the world’s most common severe monogenic disorders affecting millions of people worldwide and represents a significant public health problem. A single mutation in the β-hemoglobin gene enables deoxyHbS to polymerize and initiate the complex pathophysiology of SCD, including impaired biorheology and increased adhesion-mediated vaso-occlusion, hemolysis-mediated endothelial dysfunction, and inflammation. The current understanding of the cellular, molecular, and biophysical mechanisms of SCD and basic science and clinical studies over the past decade has inspired the development of several current and potential future therapeutic approaches to prevent disease morbidity.