Patients with Asian-type DEL can safely be transfused using RhD-positive blood
Yanli Ji, Yalin Luo, Jizhi Wen, Yuanfan Sun, Shuangshuang Jia, Chun‐Quan Ou, Wen‐Bin Yang, Jingwang Chen, Han-shen Ye, Xiangfu Liu, Yong-Neng Liang, Zhigang Lu, Ying Feng, Xinzhong Wu, Muzhou Xiao, Jian-kun Mo, Zhenhai Zhou, Zhen Wang, Zhijian Liao, Jun‐Hu Chen, Ling Wei, Guangping Luo, Sentot Santoso, Yann Fichou, Willy A. Flegel, Chao‐Peng Shao, Chengyao Li, Rui Zhang, Yongshui Fu
Abstract
Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; 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 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). 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 after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.