English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

66 Treatment of sickle cell disease (SCD) remains varied with only a minority of patients benefiting from stem cell transplant as a near cure. Others await the promise of more effective and less toxic treatments than hydroxyurea, especially children who are most susceptible to the morbidities and mortalities of SCD. The recent report of Hebert, Rakotoson et al. [1] points to an evolution of in vitro diagnostics (IVD) testing of blood cells with the emerging need for cell-by-cell measurement of red blood cell (RBC) specific hemoglobin variant levels. The study further provides clinical validation as to the utility of measuring HbF content in RBCs of SCD patients, not just as a prognostic test, but likely serving as a companion diagnostic in phase 3 clinical trials of new SCD therapies. The assay described by the French group is an “off label” adaptation of a CE-IVD flow cytometric assay kit (Fetal Cell Count Kit, IQ Products, Groningen, NL), based upon anti-HbF monoclonal antibody detection and multiparameter flow cytometry. The original intended use of the kit is to measure fetomaternal hemorrhage (FMH) as a companion diagnostic for the use of Rh immune globulin therapy to prevent hemolytic disease of the newborn, where the target analyte is fetal RBCs, rather than adult RBCs containing lower HbF levels, so-called F cells. Heretofore interest in red cell hemoglobin levels related only to total cellular hemoglobin expressed as a simple mean level across the entire blood RBC population, although the importance of HbF levels correlating with the reduction of SCD complications had been previously appreciated [2-4]. Routine blood cell counters largely provide a calculated, albeit reasonably precise, parameter of mean cell hemoglobin (MCH), that is included in most clinical algorithms for anemia differential diagnosis. Only cell-by-cell hemoglobin determinations when applied to the reticulocyte population has found niches of clinical utility, such as in the management of anemia and erythropoietin therapy associated with chronic renal disease [5]. Understanding the HbF RBC levels is poised for a clear role in the personalized care and therapeutic management of sickle cell disease (SCD) patients, long known to be a genetically and clinically heterogenous patient population [6,7]. The recent enthusiasm regarding molecular therapeutic strategies affecting the fetal to adult hemoglobin switching mechanisms [8-14] and importance of understanding the level of fetal hemoglobin (HbF) within the cell as a major moderator of hemoglobin polymerization and hence sickling conformational changes is clearly demonstrated by the work of the French group [1].

Needed, Assays for “Fetal Hemoglobin levels” in RBCs: Fetomaternal Hemorrhage and Expanded Applications in Sickle Cell Disease Management Could Forge an Evolution in Cellular Diagnostics