The perfusion paradox and vascular instability in sickle cell disease

Sickle cell disease (SCD) exhibits a curious coexistence of contrasting perfusion profiles in the circulatory system: hypoperfusion is endemic in microcirculatory beds occluded by hemoglobin S-containing erythrocytes while hyperperfusion characterizes the systemic (macro)circulation and a number of regional vascular circuits. This review highlights this perfusion paradox of SCD, focusing on forearm blood flow and the renal circulation, and exploring the extent to which alterations in vasoactive system (such as nitric oxide and prostanoids) are involved. Also reviewed are the mechanisms and pathways that contribute to altered vascular reactivity and vascular instability observed in SCD. Finally, the possibility that the induction of heme oxygenase-1, recently described in SCD, may confer a protective response in the vasculature and other tissues is discussed.