WASHINGTON – For male patients with sickle cell disease, priapism can be more than just painful and embarrassing. The prolonged erections prompted by vasoocclusive events in the penis may lead to irreversible impotence, but little is known about risk factors for priapism, which remains a difficult-to-treat complication of the disease.
In males with HbSS sickle cell disease (SCD) and priapism, RBC adhesion is increased in hypoxic conditions, according to preliminary findings from work using a newly developed biochip that mimics microvascular conditions in SCD. This significant level of adhesion prompted by hypoxia was not seen in men who did not have priapism, according to study coauthor Erina Quinn, a research assistant in hematology and oncology at Case Western Reserve University, Cleveland, who presented the results at the annual meeting of the Foundation for Sickle Cell Disease Research.
When hemoglobin desaturation occurs, polymerization can be increased, leading to increased end-organ damage, Ms. Quinn said. The biochip is “an effort to measure cellular adhesion in a clinically meaningful way.” The tool can detect hemoglobin phenotype, differentiating among HbSS, HbSbeta+, and HbSC. It can also measure the degree of hemolysis and RBC deformability.
The biochip “mimics postcapillary flow conditions in microchannels,” Ms. Quinn said. The device forces blood samples through microchannels that are at the diameter of smaller venules, approximately 50 mcm, and at a physiological flow rate ranging from 1-13 mm/sec. The microfluidic channels are coated with laminin, a subendothelial matrix protein implicated in RBC adhesion. A second microfluidic biochip mimics hypoxic conditions.
The study enrolled 26 men with the HbSS genotype, 14 of whom reported priapism, and assessed RBC adhesion in blood samples run though both the SCD-modeled biochip and the hypoxia biochip. Investigators also assessed contemporaneous in vivo hemoglobin desaturation, and looked for associations with the in vitro biochip findings.
Of the 26 participants, 16 also had either nocturnal or exertional hemoglobin desaturation. In addition, 10 participants had both priapism and desaturations. These data were collected by retrospective chart review and patient survey.
Patients with priapism were a mean age of 34 years, compared with a mean age of 29 years for the other participants, a nonsignificant difference. There were no significant differences in mean hemoglobin or bilirubin levels, or in reticulocyte counts, between the two groups.
However, white blood count, absolute neutrophil count, and lactate dehydrogenase levels were significantly higher for men with priapism (P = .022, .037, and .008, respectively). Ferritin levels were higher as well, at a mean 2,433 (plus or minus 2,234) mcg/L for those with priapism, compared with a mean 269 (plus or minus 3,015) mcg/L for those without priapism (P = .031).
When absolute reticulocyte count was mapped against lactate dehydrogenase levels to create a measure of degree of hemolysis, “individuals with priapism had a more hemolytic lab profile,” said Ms. Quinn (P = .0186).
Though 10 of 14 men with priapism had hemoglobin desaturation, compared with 5 of 12 who did not have priapism, the difference was not statistically significant.
When the researchers compared microchip analysis of RBC adhesion, though, they found marked differences in RBC adhesion in hypoxic versus nonhypoxic conditions. Significantly more RBCs were adherent under hypoxic conditions – in the hypoxic biochip – for the patients with priapism than for patients without priapism (mean, 529 vs. 3,268 adherent cells; P = .016).