Priapism in Sickle-Cell Disease: A Hematologist's Perspective

Introduction. Priapism is a familiar problem to hematologists, well known for its association with sickle-cell disease (SCD). It also occurs in a variety of other hematological illnesses, nearly all forms of congenital hemolytic anemia, including other hemoglobinopathies and red blood cell membranopathies and enzymopathies. Aim. Provide urologists with a comprehensive review of priapism in SCD, with an emphasis on the perspective of a practicing hematologist. Methods. Medline searches through July 2010 were conducted using the terms priapism, erectile dysfunction, and sickle cell. Main Outcome Measures. Expert opinion was based on review of the medical literature related to this subject matter. Results. In men with SCD, large epidemiological studies have linked the risk of priapism to clinical markers of the severity of intravascular hemolysis. Extracellular hemoglobin and arginase released during hemolysis has been implicated in reducing nitric oxide bioavailability, although the relevance of hemolysis to vascular dysfunction has been challenged by some scientists. Consistent with the role of impairment of the nitric oxide axis, mice genetically deficient in nitric oxide production have also been shown to develop priapic activity. Provocative new data indicate that hemolysis-linked dysregulation of adenosine signaling in the penis contributes to priapism in sickle cell mice. Serious questions have arisen regarding the efficacy of mainstays of textbook dogma for treatment of acute severe priapism, including intravenous fluids, alkalinization, and exchange transfusion, and there is increasing acceptance for early aspiration and irrigation of the corpus cavernosum. Conclusion. For patients with sickle cell with recurrent priapism, there is very limited evidence for a medical prophylaxis role for hydroxyurea, etilefrine, pseudoephedrine, leuprolide, sildenafil, and other agents. Recent publications have highlighted nitric oxide and adenosine signal transduction pathways as worthy of additional research. Research and clinical management of sickle-cell priapism is strengthened by multidisciplinary collaboration between hematologists and urologists.