Figure 1.

The basic pathophysiological model of sickle vaso-occlusion suggests that microvascular occlusion will occur if the delay time from deoxygenation of HbS to polymerization (T_d 1) is shorter than the microvascular transit time (T_t), as depicted in the lower two vessels. If delay time is longer (T_d 2), or if blood is flowing faster, the red cell transition to a rigid shape takes place in a larger diameter post capillary vessel and occlusion is less likely to occur, as depicted in the top micro-vessel. Processes like nitric oxide (NO) depletion and endothelin-1 levels in the precapillary arterioles, and adhesion, inflammation, and viscosity in the post-capillary venule establish a steady state microvascular flow “tone”. Autonomic nervous system (ANS)-mediated vasoconstriction can decrease blood flow within seconds, increasing transit time and the likelihood of entrapment of rigid RBC. Image reprinted with permission from [19].