Patients with Asian-type DEL can safely be transfused using RhD-positive blood

• Published in: Blood 2023-01, Vol.191 (2), p.445-458
• Main Authors: Ji, Yanli, Luo, Yalin, Wen, Jizhi, Sun, Yuanfan, Jia, Shuangshuang, Ou, Chunquan, Yang, Wenbing, Chen, Jingwang, Ye, Hanshen, Liu, Xiangfu, Liang, Yongneng, Lu, Zhigang, Feng, Ying, Wu, Xinzhong, Xiao, Muzhou, Mo, Jiankun, Zhou, Zhenhai, Wang, Zhen, Liao, Zhijian, Chen, Junhu, Wei, Ling, Luo, Guangping, Santoso, Sentot, Fichou, Yann, Flegel, Willy A, Shao, Chaopeng, Li, Chengyao, Zhang, Rui, Fu, Yongshui
• Format: Article
• Language: English
• Subjects: Life Sciences
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022018152

Red blood cells (RBCs) of the Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) in routine testing. RhD-positive (D+) RBC transfusion for Asian-type DEL patients has been proposed but has not been generally adopted due to a lack of direct evidence regarding its safety and underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in Asian-type DEL patients; none of the recipients (0/42; 95% confidence interval, 0%-8.40%) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4,045 serologic D- pregnant women throughout China; alloanti-D was found only in true D- individuals (2.63%, 79/3,009), but not in those with Asian-type DEL (0/1,032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs following transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in Asian-type DEL patients, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as NCT03727230.