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

• Published in: Blood Vol. 141; no. 17; pp. 2141 - 2150
• 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 Albert, Shao, Chaopeng, Li, Chengyao, Zhang, Rui, Fu, Yongshui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.04.2023; The American Society of Hematology
• Subjects: Alleles; Blood Group Antigens; Blood Transfusion; Epitopes; Erythrocytes; Female; Humans; Phenotype; Pregnancy; Retrospective Studies; Rh-Hr Blood-Group System - genetics; Transfusion Medicine
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2022018152

•Patients with Asian-type DEL may safely receive D+ red cell transfusion.•Full-length RHD transcripts were identified in Asian-type DEL erythroblasts and express the complete repertoire of D epitopes like D+ cells. [Display omitted] 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. Serologically negative RhD (D–) individuals in Asia are predominantly of the RhDEL phenotype, a polymorphism that leads to heterogeneous protein expression including a small amount of full-length RhD insufficient to agglutinate red cells in vitro. These patients have traditionally received D– blood, stressing the blood supply. In a prospective clinical trial of D+ transfusion in 42 patients with RhDEL, Ji and colleagues demonstrated that none of these patients developed antibodies. In a retrospective study of over 4000 serologically D– patients, alloanti-D was found only in true D– individuals and in no patients with RhDEL, strongly suggesting that these individuals can be transfused with D+ blood.