Exploring the Potential of Population-Optimized Red Blood Cell Antigens and Platelet HLA Typing for Homologous Blood...

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.