Yurtsever Nalan, Tormey Christopher A, Bizzario Laurie, Lee Edward S
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Transfusion. 2025 Sep;65(9):1574-1579. doi: 10.1111/trf.18343. Epub 2025 Jul 17.
The Rh blood group is highly polymorphic, and individuals with RHD variant alleles can form antibodies against antigens found in the conventional RhD protein. To prevent transfusion of D+ blood to groups at risk of forming anti-D antibodies, such as women of childbearing age and newborns, our transfusion service has established protocols to accurately identify D variants that can be missed by automated testing platforms in these important patient populations.
We implemented a blood bank protocol at Yale New Haven Hospital to identify patients to perform RHD genotyping on and evaluated the effectiveness of the protocol to detect D variants in patients undergoing ABO/D typing from December 2020 to January 2024. We compared serological reactivities between automated platforms (Grifols gel column and Werfen solid phase) and traditional tube testing on patients with confirmed RHD genotyping.
Among 74 patients genotyped, 53 exhibited D variants, yielding a positive predictive value (PPV) of 71.6%. A total of 29 patients had variant D types associated with anti-D formation. Tube testing showed significantly lower reactivity compared to the gel platform (p = .0001). Solid-phase testing did not demonstrate significant differences from tube testing (p = .15).
Our findings reveal a critical "blind spot" in automated gel platforms, which may lead to misclassification of D variants. Our established protocol effectively identifies high-risk patients who need RHD genotyping by using routine tube testing. This approach aims to minimize missed cases of clinically significant D variants, ultimately improving patient safety in transfusion practices.
Rh血型系统具有高度多态性，携带RHD变异等位基因的个体可产生针对传统RhD蛋白中抗原的抗体。为防止向有形成抗-D抗体风险的人群（如育龄妇女和新生儿）输注D阳性血液，我们的输血服务机构制定了方案，以准确识别在这些重要患者群体中可能被自动化检测平台漏检的D变异体。
我们在耶鲁纽黑文医院实施了一项血库方案，以确定需要进行RHD基因分型的患者，并评估该方案在2020年12月至2024年1月期间对进行ABO/D血型分型的患者检测D变异体的有效性。我们比较了自动化平台（格里菲斯凝胶柱和沃芬固相）与传统试管检测对确诊RHD基因分型患者的血清学反应性。
在74例进行基因分型的患者中，53例表现出D变异体，阳性预测值（PPV）为71.6%。共有29例患者具有与抗-D形成相关的变异D型。与凝胶平台相比，试管检测显示反应性显著降低（p = 0.0001）。固相检测与试管检测相比未显示出显著差异（p = 0.15）。
我们的研究结果揭示了自动化凝胶平台中一个关键的“盲点”，这可能导致D变异体的错误分类。我们制定的方案通过使用常规试管检测有效地识别了需要进行RHD基因分型的高危患者。这种方法旨在最大限度地减少临床上有意义的D变异体的漏诊病例，最终提高输血实践中的患者安全性。
