Inaccurate Doses of Rh Immune Globulin After Rh-Incompatible Fetomaternal Hemorrhage—Survey of Laboratory Practice

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

“…Despite the IVD availability of highly precise cell by cell HbF RBC assays using semi-quantitative immunophenotypic flow cytometry, the mainstay of clinical practice largely remains the microscopic Kleihauer Betke Braun test, despite its high inter-observer imprecision in the range of 25-100% coefficient of variation (CV). Interestingly the College of American Pathologists (CAP), normally an advocate of improved laboratory performance, has advocated the over-dosing of Rh immune globulin as one Davis approach to mitigation of the inaccuracies of the manual test, rather than recommending the implementation of the better performing flow cytometry assay [15,16].…”

“…The second IVD device requirement is to address the actual clinical need in a format that allows both rapid testing to support SCD clinics and additionally address the Obstetrical demand for 24/7 FMH testing availability. Certainly, methods for rapid HbF RBC assays are known [12][13][14][15][16] and existing CE IVD kits for FMH could easily be modified as done in the current study, additionally modern software algorithms are feasible and advocated to provide for fully automated high precision analysis of flow cytometric files and controls [11]. These features would be requisite specifications for a commercial HbF RBC assay providing requisite rapid turnaround (< 60 minutes time to report), high precision, and moderate complexity ease of use within the laboratory workplace to allow for 24-hour availability, thus supportive of SCD outpatients clinics, patients in crisis and facilitate a more accurate adjustment of anti-D therapy in FMH patients.…”

“…Surprisingly most FMH testing remains performed with the manual microscopic method of Kleihauer Betke Braun with variable assay precision in the range of 25 ->100% (more of a qualitative assay in performance), clearly not acceptable for F cell HbF content assay, which requires the <5% CV precision afforded to rare event analysis by flow cytometry [2]. Furthermore given the IVD status of the Quick Quant (IQ Products, Groningen, NL), FETAL Cell Count (IQ Products, Groningen, NL) and Fetal HEMOGLOBIN kits (Thermo Fisher Scientific, USA); these future regulations will severely restrict the use of LDT assays that do not perform in some superior fashion compared to the commercial IVD solutions, which in FMH testing has never been reported [15,16,22]. What is the mostly likely course for an IVD company, two separate assays or a single improved assay?…”