Epidemiology and treatment of priapism in sickle cell disease

Abstract

Ischemic priapism is a common but underrecognized morbidity affecting about 33% of adult men with sickle cell disease (SCD). The onset of priapism occurs in the prepubertal period and tends to be recurrent with increasing age. Significantly, priapism is associated with an unrecognized high burden of mental duress and sexual dysfunctions. The diagnosis of priapism is clinical. Many episodes of priapism will resolve spontaneously, but when an episode lasts longer than 4 hours, the episode is considered a urologic emergency requiring quick intervention with either corporal aspiration or shunt surgery. Only 3 randomized clinical trials (stilbesterol, ephedrine or etilefrine, and sildenafil) have been conducted for secondary priapism prevention in SCD. All 3 trials were limited with small sample sizes, selection biases, and inconclusive results after completion. The current molecular understanding of the pathobiology of priapism suggests a relative nitric oxide (NO) deficiency secondary to chronic hemolysis in SCD and associated phosphodiesterase type 5 dysregulation. We posit an increase in NO levels will restore the normal homeostatic relationship between voluntary erection and detumescence. Currently, 2 randomized phase 2 trials (1 double-blind, placebo-controlled trial and 1 open-label, single-arm intervention) are being conducted for secondary priapism prevention in men at high risk for recurrent priapism (NCT03938454 and NCT05142254). We review the epidemiology and pathobiology of priapism, along with mechanistic therapeutic approaches for secondary prevention of priapism in SCD.

Priapism in a Young Adult With Sickle Cell Disease

“…Antwi-Boasiako and Campbell (2018) found that patients with SCD had lower levels of nitrous oxide, leading to hypoxia, sickling of red blood cells, and sludging of blood within the corpora cavernosa. Molecular studies have also shown a nitrous oxide deficiency with dysregulation of the phosphodiesterase-5 pathway (Idris et al, 2022). In patients with SCD, priapism occurs because of the occlusion of the outflow vessels from the corpora cavernosa by sickled cells.…”

“…Many episodes of priapism will resolve spontaneously, but it is considered a urological emergency when an episode of ischemic priapism lasts longer than 4 hr. This requires prompt recognition and quick intervention with either corporal aspiration or shunt surgery to prevent irreversible tissue damage (Idris et al, 2022). The primary goals of medical therapy for ischemic priapism are to manage pain, decompress the corporal bodies, and restore arterial blood flow, which reduces ischemia and the risk of permanent erectile tissue damage and long-term complications (Al-Omar, 2023).…”

“…Hydroxyurea and sildenafil are commonly prescribed for the prevention of priapism. Hydroxyurea helps reduce the number of priapism episodes by increasing fetal hemoglobin and generating nitric oxide (Idris et al, 2022). It is prescribed to patients with SCD who frequently have frequent pain crises, acute chest syndrome, and severe symptomatic anemia.…”

“…In addition, a lack of knowledge about priapism may contribute to patients failing to seek medical treatment or not discussing this problem with their PCP or family. Thus, the lack of understanding of priapism may contribute to the underrecognition of priapism in clinical settings (Idris et al, 2022).…”

“…Finally, NPs need to consider the possible psychological effects priapism or sexual dysfunction may have on patients (Tanabe et al, 2019). Patients with priapism can experience loneliness, embarrassment, shame, anxiety, and depression (Costa et al, 2018; Idris et al, 2022). In addition, a lack of knowledge about priapism may contribute to patients failing to seek medical treatment or not discussing this problem with their PCP or family.…”