Priapism-related biomarkers in sickle cell disease: a systematic review

Priapism is a major clinical complication of sickle cell disease (SCD), with severe sexual, reproductive, and mental health impact. There are currently no consensus diagnostic biomarkers for identifying individuals with SCD at risk of priapism before its occurrence.

To systematically review the biochemical, hematological, imaging, genetic, and rheological parameters associated with priapism occurrence among individuals with SCD.

A systematic literature search for studies investigating the association of biochemical, hematological, rheological, imaging, rheological, and genetic parameters with the occurrence of priapism in individuals with SCD was performed in the MEDLINE, Embase, and Cochrane databases, using the following terms: "priapism," "sickle cell," "biomarker," "marker," "laboratory," "radiographic," "diagnostic," and "predictive." A systematic review of the identified studies was conducted to describe the landscape of priapism-related biomarkers in individuals with SCD.

A total of 358 studies were identified, of which 14 studies were eventually selected for evidence synthesis. The selected studies were published between 2005 and 2023, with authorship spanning five continents. We identified multiple clinical parameters investigated as potential biomarker candidates for their association with priapism occurrence in patients with SCD. We classified these into biochemical (lactate dehydrogenase, bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, nitric oxide metabolites, interleukin 6), hematological (hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, reticulocyte count, leukocyte count), genetic (Klotho, TGFBR3, QAP1, ITGAV, LNC02537, NAALADL2), rheological (red blood cell deformability, aggregation index, augmentation index), and imaging parameters. However, the results were often contradictory and do not support the clinical application of any of the investigated parameters.

Several clinical and laboratory parameters have been associated with priapism occurrence in SCD; however, contradictory findings across geographical locations paint an unreliable picture of their clinical utility. Additional studies are needed to generate enough level 1 evidence in support of any of the current candidates.