Pathophysiology of vaso-occlusive crises in SCA. Sickled red blood cells and other inflammatory mediators induce the activation of vascular endothelium. The damaged and stimulated endothelium is poised to recruit leukocytes. E-selectin on the vascular endothelium generates a secondary wave of activating signals, which produces expression of Mac-1 at the leading edge of the crawling neutrophil, facilitating the capture of circulating discoid and sickled red blood cells. Reprinted from Manwani and Frenette⁵  with permission.