Proposed ICAM-1–mediated HbSS RBC adhesion mechanism in SCD. Results are consistent with a model of firm adhesion of HbSS RBCs to the vasculature in the postcapillary venules under low physiological shear, which may be mediated by initial rolling adhesion of RBCs in the capillary under high physiological shear, facilitated by ICAM-1. RBCs may form firm attachment with ICAM-1 near the low shear sites throughout the microvasculature, contributing to impaired local flow conditions, as illustrated by the dashed oval.