Priapism is a serious complication associated with Sickle Cell Disease (SCD) that may be a manifestation of underlying vasculopathy. The Centers for the Study of Complex Diseases of Childhood (CSCCD), comprising independent Comprehensive Sickle Cell Centers, demonstrated an association of priapism with hemolysis.1 Previously, we identified two groups of people with SCD based on red blood cell (RBC) adhesion under hypoxic conditions: those patients whose RBCs showed hypoxia-enhanced adhesion (HEA) and those whose did not (non-HEA).2 Patients with HEA had evidence for more hemolysis in vivo. Here, we aimed to examine (1) the association of HEA with hypoxia in vivo, and (2) RBC adhesion in normoxic and hypoxic conditions in male patients with or without a history of priapism.
This retrospective study was conducted at the Adult Sickle Cell Disease Clinic at the University Hospitals Seidman Cancer Center, in Cleveland, OH between 2015 to 2018. Blood samples were obtained from 26 male subjects (29 samples, 25 HbSS and 1 HbSS HPFH). Adhesion experiments were performed as previously reported by passing surplus whole blood through LN-immobilized microchannels at physiological conditions under both normoxic and hypoxic conditions.2,3 Adherent RBCs were then quantified with microscope after a wash step. The median value was used for data analyses from multiple samples obtained from an individual. Chart review was conducted to examine results of hypoxia testing obtained in vivo as part of routine clinical care.
Male subjects with HbSS and a history of priapism had higher HEA in comparison to subjects without a history of priapism (3268 ± 5647 vs. 122 ± 1218, p=0.016). However, there was no significant difference between RBC adhesion of the two groups under normoxic conditions (529 ± 1528 vs. 402 ± 280). More male subjects with priapism had hypoxia in vivo (10 out of 14) than subjects without priapism (5 out of 12). Compared to male subjects with a history of priapism, those without a history of priapism had lower lactate dehydrogenase levels (474 ± 267 vs. 290 ± 215, p=0.008).
Conclusions: Our data showed that subjects with a history of priapism had a higher HEA and tended to have more evidence for hypoxia in vivo than did subjects without a history of priapism. Further, male subjects with hypoxia in vivo had more HEA than did those without hypoxia in vivo (not shown). Hypoxia in vivo may cause increased RBC damage (reflected by HEA), hemolysis, nitric oxide depletion, and consequent vasculopathy, resulting in priapism. Hypoxia may be treatable, when identified in subjects with a history priapism in vivo or possibly with HEA in vitro. This could plausibly modify disease severity in some cases.
Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Blood. 20015 Nov;106(9):3264-7. doi: 10.1182/blood-2005-04-1594
Kim M, Alapan Y, Adhikari A, Little JA, Gurkan Microcirculation. 2017 Jul;24(5). doi: 10.1111/micc.12374.
Alapan Y, Kim C, Adhikari A, Gray KE, Gurkan-Cavusoglu E, Little JA, Gurkan Transl Res. 2016 Jul;173:74-91.e8. doi: 10.1016/j.trsl.2016.03.008. Epub 2016 Mar 19.
Little:NHLBI: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding.
Asterisk with author names denotes non-ASH members.