Anti‐Ku alloimmunization due to a KEL*02N.19 allele causing Kell‐null phenotype despite KEL*02 genotype prediction

Abstract Background and Objectives Alloantibodies against high‐prevalence antigens can create significant barriers to transfusion, particularly in patients with complex medical needs. Serological investigations include use of enzyme‐treated red cells and dithiothreitol (DTT) testing, which can enhance or diminish antibody reactivity, providing insight into potential antibody specificity. Additionally, molecular testing can predict the absence of a common antigen and identify the corresponding antibody. Materials and Methods We describe the case of a Palestinian woman with cancer who had previously received compatible red blood cell (RBC) transfusions at Sheikh Shakhbout Medical City (SSMC) without complications. Upon readmission for a new chemotherapy cycle, pre‐transfusion testing revealed a panagglutinin reactive with most reagent red cells, suggesting an alloantibody directed against a high‐prevalence antigen. Enzyme‐treated cells, 2‐aminoethylisothiouronium bromide hydrobromide (AET) and DTT testing suggested involvement of the Kell blood group system. Molecular genotyping failed to predict antigen absence. However, the discrepancy between predicted phenotype and serologically determined phenotype at SSMC and Versiti Blood Center of Wisconsin led us to suspect an exon variant in the KEL gene. Results A KEL*02N.19 allele causing absence of Kell antigens was identified. The absence of reactivity with three examples of K 0 reagent red cells and with artificially created K 0 K 0 cells confirmed a K 0 phenotype with anti‐Ku. With no compatible RBC units available, a multidisciplinary team developed a non‐transfusion‐based management plan. Remarkably, the patient was able to complete her cancer treatment without requiring further transfusion. Conclusion This case illustrates the importance of integrating serological, enzymatic and molecular approaches in the identification of antibodies to high‐prevalence antigens and highlights alternative strategies to manage transfusion in complex oncology patients.