Concentration of voxelotor in sickle cell disease can be estimated using electrophoresis and high-performance liquid chromatography.

OBJECTIVES: Voxelotor can increase hemoglobin levels in patients living with sickle cell disease (SCD). A clinician who is monitoring voxelotor response may want to know whole-blood voxelotor concentration, but this cannot be measured in most clinical settings. However, voxelotor has been demonstrated to cause "peak splitting" in common methods of hemoglobin measurement such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC). We hypothesized that we could use the size of the peak split to estimate the whole-blood concentration. METHODS: Blood from people with SCD was dosed with known concentrations of voxelotor, and multiparameter regression was used to derive the relationship of voxelotor concentration to the degree of peak splitting observed. To validate these equations, 21 patients started on voxelotor at 1500 mg/d had blood samples drawn at days 0, 14, 30, and 60. Samples were sent out for gold standard voxelotor concentration testing. The derived equations were then used to calculate voxelotor concentration. RESULTS: Calculated concentrations correlated strongly with measured concentrations for both CZE (R2 = 0.83, P < .001) and HPLC (R2 = 0.76, P < .001). Voxelotor concentration also had a significant effect on increases in hemoglobin (R2 = 0.40, P < .001). CONCLUSIONS: Thus, peak splitting CZE and HPLC can be used to estimate voxelotor concentration.

COVID19 vaccination in adults with sickle cell disease is not associated with increases in rates of pain crisis.

ABSTRACTPeople with sickle cell disease (SCD) are more vulnerable to hospitalization, pneumonia, and pain following COVID-19 infection. However, given the association between the inflammatory response and vaso-occlusive crises in SCD and a case report of vaso-occlusive crises following administration of the ChAdOx1 nCov-195-7/AstraZeneca vaccine, there is concern that the administration of COVID-19 vaccines in people with SCD might provoke a vaso-occlusive crisis. To address this critical gap in knowledge, we sought to examine acute care usage for vaso-occlusive crisis and frequency and severity of side effects following COVID-19 vaccination among patients at the Montefiore Sickle Cell Center for Adults. As part of regular care, patients were asked if they had received COVID-19 vaccination and any side effects were noted. Electronic medical records were reviewed for the type of vaccine, dates received, episodes of vaso-occlusive crises within seven days of a dose, and side effects noted. The risk of average hospital utilization per week in 2019 was calculated as a baseline. We found that fewer than 1 in 10 patients presented to the hospital within seven days of vaccination and that the risk of hospital utilization was similar to the average risk in a week in 2019. Of patients who reported side effects, one reported a possible case of sensorineural hearing loss otherwise no other rare side effects, including thrombosis or death, were reported.