Which factor can cause false negative ABO grouping, necessitating further testing for an ABO variant?

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A false negative ABO grouping can occur when an ABO variant changes how A or B antigens are expressed on red cells. Standard typing using routine antisera may not detect these variant antigens because their epitopes are weakened or altered, leading to a weaker or negative reaction even though an antigen is present. In such cases, routine testing can misclassify the blood, so specifically testing for an ABO variant is needed to determine the true type before transfusion.

ABO variants include weak subgroups and other rare allele expressions that reduce antigen density or alter epitopes, or situations like Bombay-like phenotypes that affect antigen presence. Because these aren’t resolved by normal typing, more specialized testing—such as extended serology with additional antisera, adsorption/elution studies, or molecular genotyping—is used to confirm the correct ABO type and ensure safe matching.

Other technical issues, like IgG coating of cells, dilute suspension, or wrong reagents, can affect results but are generally addressed by repeating the test or ensuring proper technique rather than indicating an ABO variant needing dedicated testing.