Vaso-occlusion in sickle cell anemia: role of interactions between blood cells and endothelium.

Abstract

Sickle cell anemia (SCA) is one of the most common inherited blood disorder. It has been defined as a molecular disease more than 50 years ago and since then has given rise to an enormous amount of investigations. SCA is usually characterized by three major features, namely hemolytic anemia, painful vaso-occlusive crises (VOC) and susceptibility to infections. Other potentially life-threatening complications include splenic sequestration, acute chest syndrome, and stroke. Finally, evolution during adulthood, now commonly observed, is complicated by chronic organ damage. Despite a unique mutation in the beta-globin gene and a common basic mechanism based upon the polymerization of deoxyhemoglobin S (Hb-S) and vaso-occlusion by sickled red blood cells, its phenotypic expression is highly variable, and the occurrence of the major complications is unpredictable. Most particularly, events triggering vaso-occlusion still remain largely unknown. In the recent years, the discovery of an abnormal adhesion of sickle red blood cells to the vascular endothelium has provided important new insights. It is clear now that all the circulating cells as well as the endothelium are part of the phenomenon and that cell activation and inflammatory processes play a major role in the pathogenesis of the disease.