Abstract Background Sickle cell disease (SCD) consists of hemoglobinopathies caused by genetic mutations resulting in defective hemoglobin formation. These conditions have significant morbidity and mortality, such as vasoocclusive crisis, organ damage, and hemolysis. Early disease detection is critical for initiation of disease-modifying therapy to prevent these complications. Typical screening for hemoglobin variants using hemoglobin electrophoresis testing is not easily accessible to many areas of the world, such as low-income settings, where SCD is most prevalent, and many children do not have standard screening for hemoglobinopathies. Point-of-care (POC) devices have been developed to facilitate the rapid and cost-effective screening and monitoring of SCD, particularly in low-resource settings. The Gazelle POC instrument, which utilizes a cellulose acetate membrane to resolve hemoglobin variants into four distinct bands—A, F, S, and A2CE—has been evaluated in limited populations. However, its accuracy compared to conventional hemoglobin electrophoresis methods remains to be fully established, especially in pediatrics. This study aims to validate the analytical and clinical performance of the Gazelle POC instrument to determine its reliability for SCD screening and monitoring using pediatric samples. Methods Validation studies, including precision, linearity, and method comparison, were conducted. Precision was assessed by analyzing four control materials, Bio-Rad LyphoChek levels 1 and 2, as well as Sickle-Chex® positive and negative, once daily for 10 days. Linearity was evaluated using mixing studies with samples containing elevated hemoglobin F, A, and S concentrations. Method comparison was performed by analyzing 40 whole blood specimens using both the Sebia Capillarys system and the Gazelle® instrument. Results Precision analysis demonstrated significant variation in %CV depending on the hemoglobin variant measured. For Sickle-Chex® positive, the %CV was 24% and 19% for hemoglobin F and S, respectively, but was notably higher for the Hb A2CE band and Hb F. For Sickle-Chex® negative, the %CV was 6% and 10% for Hb A and F, respectively. Bio-Rad LyphoChek level 1 exhibited a %CV greater than 39% for all hemoglobin variant bands, while Bio-Rad LyphoChek level 3 showed %CVs of 18% and 17% for Hb A and S, respectively. Linearity studies demonstrated strong performance for Hb A (R² = 0.95), while Hb F and the A2CE band exhibited weaker linearity, with R² values of less than 0.9. Method comparison studies revealed strong correlations (R² 0.95) for Hb A, F, and S between the Gazelle® instrument and the Sebia Capillarys system. Conclusion The Gazelle® POC device demonstrated adequate clinical and analytical performance for measuring hemoglobin variants, with performance varying by hemoglobin band or variant. These findings support its potential use for SCD screening and monitoring, particularly in low-resource settings, though further validation in diverse populations may be warranted.
Wilson et al. (Wed,) studied this question.