Priapism, hemoglobin desaturation, and red blood cell adhesion in men with sickle cell anemia

Priapism is a serious, but episodic, complication of sickle cell disease (SCD). We had previously reported that subjects with SCD had variable red blood cell (RBC) adhesion to the immobilized sub-endothelial protein laminin (LN). We examined adhesion to LN in a microfluidic device, of RBCs from men with homozygous sickle cell anemia. Adhesion under hypoxic, but not ambient, conditions was greater in men with a history of priapism, with median adhesion of 529 RBCs per 32 mm²/unit area (range 5-5248) rising to 3268 RBCs per 32 mm²/unit area (range 49-18,368, P = 0.004), under ambient and hypoxic conditions, respectively (n = 14). This was not seen in RBCs from men without a history of priapism (median 402 (range 14-785) and 122 (range 31-4112) RBCs per 32 mm²/unit area, ambient and hypoxic conditions, respectively (P = N.S., N = 12)). We also observed an association between hypoxia-enhanced RBC adhesion in vitro and a history of hemoglobin desaturation in vivo independent of priapism. Prolonged Hb desaturation may increase sickle polymer formation and RBC damage, resulting in enhanced RBC adhesion, hemolysis, and endothelial dysfunction. The identification of distinct RBC phenotypes could prompt clinical evaluation for suitability for novel or under-used therapies, like oxygen.