Vascular occlusion in sickle cell disease: current concepts and unanswered questions

HE SICKLE CELL diseases (SCD) are inherited T disorders of hemoglobin (Hb) structure and synthesis, and include homozygous sickle cell anemia (Hb SS), sickle-(= disease (Hb SC), double-heterozygous combinations of Hb S and P-thalassemia (Hb S-thal), and other less common variants. The clinical manifestations of SCD include chronic hemolysis, frequent infections, and a variety of other acute and chronic complications that produce organ damage, disability, and death (Tables 1 and 2). Although current thinking suggests that microvascular occlusion by poorly deformable sickle erythrocytes (SS RBC) is a key pathophysiologic event in SCD, the mechanism(s) of microvascular obstruction and the role of other vasocclusive processes such as vascular intimal hyperplasia, thrombosis, and vasospasm are not fully defined. This review seeks to summarize and critically evaluate current concepts regarding the cause(s) and consequences of vascular occlusion in SCD. Despite substantial recent progress, it is increasingly apparent that vascular occlusion in SCD is a very complex, multifactorial process, and that many important questions remain unanswered. OVERVIEW