The sickle mutation results from a single nucleotide change (GAT → GTT) in the sixth codon of exon 1 of the β-globin chain. Consequently, the normal glutamic acid at position 6 of the β-globin chain is replaced by valine, thus leading to the formation of sickle hemoglobin (Hb S). Sickle cell anemia (SS) is the homozygous state in which the sickle gene is inherited from both parents. It is rather surprising that a single base substitution in the 3 billion base pairs of human genome leads to a complex disease process that involves multiple organs. Detailed understanding of the pathophysiology of the disease involves multiple scientific disciplines including molecular biology, cell biology, biophysics, clinical medicine, and psychosocial medicine. The situation is similar, metaphorically speaking, to the occurrence of a simple typographic error in a key word that results in distorting the message of a whole manuscript.

This article reviews the contribution of vaso-occlusion to the pathophysiology of the disease. It discusses the role of the rheologic and adherence properties of sickle erythrocytes to vascular occlusion and their impact on the clinical, laboratory, and therapeutic aspects of SS.