Priapism in Sickle Cell Anemia: Emerging Mechanistic Understanding and Better Preventative Strategies
Figure 1
Abnormal nitric oxide signaling leads to priapism in SCD. NO can be readily scavenged by free hemoglobin and deactivated by conversion to nitrate. This is normally prevented by compartmentalization of hemoglobin in red cells and a cell free zone adjacent to the endothelium ((a), first panel adapted from Liao [9] and Rother et al. [23]). In SCD, chronic hemolysis leads to higher levels of free hemoglobin and decreased NO availability. This results in decreased basal levels of its downstream effector, cGMP, and decreased PDE5, which degrades cGMP. Following cavernosal nerve stimulation in SCD (b), normal levels of cGMP are achieved as NO is released from nerve terminals. However, PDE5 levels remain low, leading to prolonged cGMP activity and prolonged erection. This can be prevented by long-term treatment with sildenafil ((b), second panel). Inhibition of PDE5 by sildenafil results in increased cGMP, which then increases basal PDE5 levels through normal feedback mechanisms [13, 14].
