SEARCH WITHIN CONTENT
Citation Information : Immunohematology. Volume 33, Issue 3, Pages 125-132, DOI: https://doi.org/10.21307/immunohematology-2019-019
License : (Transfer of Copyright)
Published Online: 09-October-2019
DEL red blood cells (RBCs) type as D– by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D– recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D– Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D– Caucasian populations (0.1%). Among the 3–5 percent of African individuals who are D–, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D– recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68–683 units of DEL RBCs from donors of East Asian ancestry are transfused as D– annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D– recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.
1. Okubo Y, Yamaguchi H, Tomita T, Nagao N. A D variant, Del? Transfusion 1984;24:542.
2. Okubo Y, Seno T, Yamano H, et al. Partial D antigens disclosed by a monoclonal anti-D in Japanese blood donors. Transfusion 1991;31:782.
3. Fukumori Y, Hori Y, Ohnoki, et al. Further analysis of Del (D-elute) using polymerase chain reaction (PCR) with RHD gene-specific primers. Transfus Med 1997;7:227–31.
4. Wagner FF, Frohmajer A, Flegel WA. RHD positive haplotypes in D negative Europeans. BMC Genet 2001;2:10.
5. Shao CP, Maas JH, Su YQ, et al. Molecular background of Rh D-positive, D-negative, D(el) and weak D phenotypes in Chinese. Vox Sang 2002;83:156–61.
6. Shao CP. Transfusion of RhD-positive blood in “Asia type” DEL recipients. N Engl J Med 2010;362:472–3.
7. Singleton BK, Green CA, Kimura K, et al. Two new RHD mutations associated with the Del phenotype (abstract). Transfus Clin Biol 2001;8(Suppl 1):9s.
8. Dunnen JT, Dalgleish R, Maglott DR, et al. HGVS recommendations for the description of sequence variants: 2016 Update. Human Mutat 2016;37:564–9.
9. Chen J-C, Lin T-M, Chen YI, et al. RHD 1227A is an important genetic marker for RhDel individuals. Am J Clin Pathol 2004;122:193–8.
10. Shao CP, Xu H, Xu Q, et al. Antenatal Rh prophylaxis is unnecessary for “Asia type” DEL women. Transfus Clin Biol 2010;17:260–4.
11. Chang JG, Wang JC, Yang TY, et al. Human RhD el is caused by a deletion of 1013 bp between introns 8 and 9 including exon 9 of RHD gene (letter). Blood 1998;92:2602–4.
12. Luettringhaus TA, Cho D, Ryang DW, Flegel WA. An easy RHD genotyping strategy for D– East Asian persons applied to Korean blood donors. Transfusion 2006;46:2128–37.
13. Wagner FF. RHD PCR of D-negative blood donors. Transfus Med Hemother 2013;40:172–81.
14. Wagner FF, Flegel WA. The rhesus site. Transfus Med Hemother 2014;41357–63. (The human RhesusBase, version 2.0. http://www.rhesusbase.info/, update 2017-02-19.)
15. Shao C, Wang B, Ye S, et al. DEL RBC transfusion should be avoided in particular blood recipient in East Asia due to allosensitization and ineffectiveness. J Zhejiang Univ Sci B 2012;13:913–8.
16. Yang HS, Lee MY, Park TS, et al. Primary anti-D alloimmunization induced by “Asian type” RHD (C.1227G>A) DEL red cell transfusion. Ann Lab Med 2015;35:554–6.
17. Li Q, Hou L, Ye LY, et al. Molecular basis of the RHD gene in blood donors with DEL phenotypes in Shanghai. Vox Sang 2009;97:139–46.
18. Ji YL, Van der Schoot CE. Red blood cell genotyping in China. ISBT Sci Ser 2016;11:55–68.
19. Gu J, Wang X, Shao C, et al. Molecular basis of DEL phenotype in the Chinese population. BMC Med Gen 2014;15:54.
20. Yang YE, Wang YH, Chen JC, et al. Prevalence of RHD1227A and hybrid rhesus in the general Chinese population. Translat Res 2007;149:31–6.
21. Okuda H, Kawano M, Iwamoto S, et al. The RHD gene is highly detectable in RhD-negative Japanese donors. J Clin Invest 1997;100:373–9.
22. Kim YJ, Kim YS, Kim C, et al. Molecular characterization of D– Korean persons; development of a diagnostic strategy. Transfusion 2005;45:345–52.
23. Kim K, Kim K, Wook K, et al. Primary anti-D immunization by DEL red blood cells. Korean J Lab Med 2009;29:361–5.
24. Flegel WA, Zabern IV, Wagner FF. Six years’ experience performing RHD genotyping to confirm D– red blood cell units in Germany for preventing anti-D immunizations. Transfusion 2009;49:465–71.
25. Daniels G. Human blood groups. 2nd ed. Malden, MA: Blackwell Science, 2002.
26. Wagner FF, Ladewig B, Angert KS, Heymann GA, Eicher NI, Flegel WA. The DAU allele cluster of the RHD gene. Blood 2002;100:306–11.
27. Mak KH, Yan KH, Cheng SS, Yuen MY. Rh phenotypes of Chinese blood donors in Hong Kong, with special reference to weak D antigens. Transfusion 1993;33:348–51.
28. Wagner T, Körmöczi GF, Buchta C, et al. Anti-D immunization by DEL red blood cells. Transfusion 2005;45:520–6.
29. von Zabern I, Flegel WA. IVS5-38del4 deletion in the RHD gene does not cause a DEL phenotype: relevance for RHD alleles including DFR-3. Transfusion 2007;47:1552–5.
30. Yasuda H, Ohto H, Sakuma S, et al. Secondary anti-D immunization by Del red blood cells. Transfusion 2005;45:1581–4.
31. Körmöczi GF, Gassner C, Shao CP, et al. A comprehensive analysis of DEL types: partial DEL individuals are prone to anti-D alloimmunization. Transfusion 2005;45:1561–7.
32. Flegel WA. Response to: Are weak D RBCs really immunogenic? (letter). Transfusion 2006;46:1063–4.
33. Wang QP, Dong GT, Wang XD, et al. An investigation of secondary anti-D immunization among phenotypically RhDnegative individuals in the Chinese population. Blood Transfus 2014;12:238–43.
34. Wang M, Wang BL, Xu W, et al. Anti-D alloimmunization in pregnant women with DEL phenotype in China. Transfus Med 2015;25;163–9.
35. Xu W, Zhu M, Wang BL, et al. Prospective evaluation of a transfusion policy of RhD-positive red blood cells into DEL patients in China. Transfus Med Hemother 2015;42:15–21.
36. Gardener GJ, Legler TJ, Hyett JA, et al. Anti-D in pregnant women with the RHD(IVS3+1G>A)-associated DEL phenotype. Transfusion 2012;52:2016–9.
37. Wang YH, Chen JC, Lin KT, et al. Detection of RhD(el) in RhD-negative persons in clinical laboratory. J Lab Clin Med 2005;146:321–5.
38. Seo MH, Won EJ, Hong YJ, et al. An effective diagnostic strategy for accurate detection of RhD variants including Asian DEL type in apparently RhD-negative blood donors in Korea. Vox Sang 2016;111:425–30.
39. Ogasawara K, Suzuki Y, Sasaki K, et al. Molecular basis for D– Japanese: identification of novel DEL and D-alleles. Vox Sang 2015;109:359–65.
40. Gu J, Wang X, Shao C, et al. Molecular basis of DEL phenotype in the Chinese population. BMC Med Genet 2014;15:54.
41. Li Q, Ye LY, Guo ZH, Zhang YX, et al. Molecular basis of D variants between Uigur and Han blood donors in Xinjiang. Transfus Med 2008;18:199–203.
42. Wu JJ, Hong XZ, Xu XG, et al. RHD 1227A allele frequency among Rh negative population and random population. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:1234–7.
43. Hoeffel EM, Rastogi S, Kim MO, Shahid H. The Asian population: 2010. Suitland, MD: United States Census Bureau, 2010.
44. Wu X, Wu D, Wang M, et al. Analysis of frequency of a RHD1227A allele in Chinese Hans (abstract). Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2014;31:793–6.
45. Li JH, Zhang CY, Sun LH, Liu J. Molecular mechanisms of RhDel phenotype in blood donation population of Chinese Harbin area (abstract). Zhongguo Shi Yan Xue Ye Xue Za Zhi (Chinese) 2012;20:1478–81.
46. Chen Q, Li M, Li M, et al. Molecular basis of weak D and DEL in Han population in Anhui Province, China (abstract). Chin Med J (Engl) 2012;125:3251–5.
47. Sun CF, Liu JP, Chen DP, et al. Use of real time PCR for rapid detection of Del phenotype in Taiwan. Ann Clin Lab Sci 2008;38:258–63.
48. Yazer MH, Vassallo R, Delaney M, et al. Trends in age and red blood cell donation habits among several racial/ethnic minority groups in the United States. Transfusion 2017;57:1644–55.
49. Yazer MH, Delaney M, Germain M, et al. Trends in US minority red blood cell unit donations. Transfusion 2017;57:1226–34
50. Flegel WA, Castilho SL, Keller MA, et al. Molecular immunohematology round table discussions at the AABB Annual Meeting, Philadelphia 2014. Blood Transfus 2016; 14:425–33.
51. Garratty G. Do we need to be more concerned with weak D antigens? Transfusion 2005;45:1547–51.
52. Denomme GA, Flegel WA. Applying molecular immunohematology discoveries to standards of practice in blood banks: now is the time. Transfusion 2008;48:2461–75.