Ischemia-reperfusion injury in sickle cell anemia: Relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain

Ischemia-reperfusion (I/R) physiology, also called reperfusion injury, instigates vascular and tissue injury in human disease states. This review describes why sickle cell anemia should be conceptualized in this fashion and how I/R physiology explains the genesis of characteristic aspects of vascular pathobiology and clinical disease in sickle cell anemia. The nature of I/R and its relevance to sickle cell anemia are discussed, with an emphasis on the acute chest syndrome, endothelial dysfunction with aberrant vasoregulation, circle of Willis vasculopathy, and inflammatory pain. Viewing sickle disease from this perspective elucidates defining pathophysiology and identifies a host of novel potential therapeutic targets.