Exploring the Potential of Population‐Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood Transfusion Detection in Japanese Athletes

ABSTRACT

Homologous blood transfusion (HBT) doping, using donor red blood cells (RBCs) to enhance oxygen capacity, remains a persistent challenge for doping control laboratories, especially in specific populations. Current RBC antigen‐based flow cytometric detection (double population, DP) has limited sensitivity in genetically homogeneous populations due to common phenotypic overlap. This study aimed to enhance HBT detection by optimizing population‐specific RBC antigen panels and incorporating complementary platelet‐derived human leukocyte antigen (HLA) markers. Based on antigen‐negative frequency, M, N, and Le ^b antigens were evaluated as candidate markers for improved discrimination in the Japanese population. In simulated HBT samples with a 5% mixing ratio, N antigen showed a clearly separated bimodal distribution, indicating strong potential for DP detection. Although Le ^b antigen showed unclear DP, M antigen displayed uniformly high expression, useful for distinguishing expressing populations. In addition, platelet HLA analysis, especially targeting HLA‐A24, enabled detection of donor‐derived components even with identical RBC antigen phenotypes. Mixed samples containing as low as 1%–5% donor cells produced visually detectable DP signals in the platelet gate. In conclusion, integrating a race‐tailored RBC antigen panel with complementary platelet HLA monitoring may provide a potentially improved framework for HBT detection, particularly in ethnically homogeneous populations like Japan. The optimal antigen panel is highly population‐specific due to genetic variations, requiring adaptation for other diverse ethnic groups. Future cohort studies are warranted to validate this dual approach and refine detection sensitivity.