SAGE IVD recommended including the Kleihauer-Betke acid-elution test category in EDL 4
• as a general IVD for use in clinical laboratories (EDL 4, Section II.a);
• using microscopic examination of slides which may use different types of microscopes and stains;
• using whole blood as specimen type;
• to aid in the diagnosis and treatment of fetomaternal haemorrhage (FMH).

The KB acid-elution test measures the presence of fetal blood in the maternal circulation. The test is extremely valuable in LMICs where FMH is suspected and the gold standard (flow cytometry) is scarcely available. The KB test is also used to determine the appropriate dose of anti-D immunoglobulin to give a mother to prevent problems related to blood incompatibility when there has been mixing of fetal and maternal blood. The KB test is easy to use, but it is microscopy based, which means that it requires a high standard of laboratory training. The test also only picks up more than 5 mL of bleed. Flow cytometry provides a more accurate quantification of the amount of haemorrhage, but it is expensive and is usually done in a tertiary institution. SAGE IVD members emphasized that this characteristic is true for high-income countries as well as LMICs. One SAGE IVD member noted that a colleague in Australia reports doing 14 000 KB tests per year for FMH vs 30 flow cytometry tests. One expert raised a concern about availability of anti-D immunoglobulin in LMICs and whether it makes sense to include the KB test in the EDL if the therapy is actually difficult to get. Experts working in India and Mexico reported that supplies of immunoglobulins in their countries could be unreliable. But it was pointed out that anti-D immunoglobulin has consistently appeared on essential medicine lists across the globe for years and is likely to be generally available. SAGE IVD noted that the submission did lack a clear algorithm. Group members also questioned the quality of the evidence provided in the application, and specifically the lack of a direct comparison with flow cytometry. However, these concerns were not judged substantial enough to affect the decision to list. Ultimately, SAGE IVD members agreed that the KB test is critical to have, especially to save the lives of babies and mothers in LMICs where access to flow cytometry is uncertain or nonexistent. In the statement of test purpose, SAGE IVD recommended replacing “prognosis” with “treatment” to avoid giving the impression that the test predicts outcome. Literature cited in the discussion: Thorpe SJ, Sands D, Fox B, Behr-Gross ME, Schaffner G, Yu MW. 2nd WHO international standard for anti-D immunoglobulin. Geneva: World Health Organization; 2003 (WHO/Bs03.1962; https://apps.who.int/iris/handle/10665/ 67735, accessed 14 December 2022). WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/ 10665/250796, accessed 14 December 2022).

Considering the fact that flow cytometry is not always available, this very easy, less accurate test can save lives. While flow cytometry may be more accurate, it is not readily available in all clinical situations and treatment may be delayed or inadequate without access to the KB test. The test kit is not too expensive.

World Health Organization. (‎2023)‎. The selection and use of essential in vitro diagnostics: report of the fourth meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2022 (‎including the fourth WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/373322