Precision diagnostics in Transfusion Medicine: Advancing accuracy in Bombay blood group typing through molecular methods

Background: Integration of precision diagnosis in Immunohaematology and Transfusion Medicine has led to the development of more refined blood typing and crossmatching techniques, ensuring improved accuracy of blood group determination, thereby reducing the incidence of transfusion reactions and enhancing patient safety. It can also help resolve complex discrepancies noted in serological testing methods. Study design and methods: The blood grouping of a 40 year old female patient done as a part of routine health check using column agglutination technology showed a O group phenotype with additional reaction with O cells in the serum group. Anti-H lectin study confirmed the absence of H antigen, with a Lewis Le(a+b-) phenotype, typing the patient as Classical Bombay phenotype. Further molecular workup was performed. Results: An in-house designed panel enabling comprehensive genotyping for 45 blood group systems and transcription factors KLF1 and GATA1 was used. Sequencing covering the ABO gene predicted the presence of the ABO*O.01.01 and ABO*O.01.02 alleles and the group O phenotype. Combined results of the sequencing analysis identified ABO*O.01.01/*O.01.02, FUT1*01N.09/*01N.09 and FUT2*01/*01 with the predicted phenotype of H-deficient; secretor (para-Bombay). Oh-secretor shows the patient is genetically a ParaBombay since there is an active secretor gene, but phenotyped as Le(a+b-) due to the reduction in Lewis enzyme function by the FUT3 mutations. Hence the patient is classified as a paraBombay, even though the Lewis phenotype make the patient appeared to be a classical Bombay. Conclusion: Integration of precision diagnostics into transfusion therapy improves transplant and transfusion safety.