Sickle cell disease: looking back but towards the future

Abstract

Sickle cell disease (SCD) is a multisystem disease associated with episodes of acute illness and progressive organ damage, and one of the most common monogenic disorders worldwide, affecting an estimated 30 million people. SCD represents a major public health problem because of its associated morbidity and mortality(1,2). Last year marked the 100th year since SCD was first described by James B. Herrick. The myriad clinical features of this hemolytic anemia result from a deceptively simple amino acid substitution of valine for glutamic acid in the sixth position of the s-subunits of hemoglobin (Hb). The result is intracellular polymerization under conditions of hypoxia and dehydration, which triggers the characteristic sickle-shaped erythrocytes(3). Modern advances in molecular and cellular biology have resulted in an accumulation of data on the sickle cell pathophysiology related to erythrocyte and extra-erythrocyte events(1). Since the seminal discovery by Dr. Herrick, we have learnt that SCD is as much a disease of endothelial dysfunction as it is a hemoglobinopathy. Oxidative stress, chronic endothelial damage and hemolysis initiate a cascade of events that result in episodic vaso-occlusion, subsequent ischemia-reperfusion injury, inflammation and organ dysfunction(3).