Regional

Let us advance research to transform scientific discoveries into clinical benefits for Asian-type DEL carriers

Yanli Ji

Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China

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The Asian-type DEL is the most prevalent DEL variant worldwide. First described by Shao CP in 20101, this variant is specifically distributed among East and Southeast Asian populations and the immigrants from this population, hence termed as Asian-type DEL. In regions including East/Southeast Asia (China, Japan, South Korea, Thailand, and Myanmar etc.), the United States, and the European Union (EU), the Asian-type DEL allele is carried by ~96%, 77%, and 9% of DEL populations, respectively, affecting approximately two million, 90,000, and 10,000 individuals in these regions2,3.

The clinical management of Asian-type DEL carriers—particularly transfusion recipients and pregnant women—has been debated since its molecular basis was elucidated over two decades ago. In 2006, Willy Albert Flegel proposed D+ RBC transfusion for all Asian-type DEL patients4. This approach gained support when Shao CP’s 2010 study detected no alloanti-D in a limited cohort of Asian-type DEL pregnant women carrying D+ fetuses1. Subsequent case reports from South Korea (20065, 20196) documented two Asian-type DEL patients who received D+ RBCs without alloanti-D immunization.

In 2023, Ji YL and colleagues7 provided robust evidence supporting the safety of D+ RBC transfusion in Asian-type DEL carriers. Their work included: 1) A first multicenter clinical trial evaluating D+ RBC transfusion outcomes in Asian-type DEL patients. 2) A large retrospective study screening for alloanti-D immunization in Chinese Asian-type DEL pregnant women. Neither study observed alloanti-D formation. Additionally, low-abundance full-length RHD transcripts (0.18% of total) expressing complete RhD epitopes were identified in Asian-type DEL erythroblasts, offering a mechanistic basis for immune tolerance to D+ RBCs.

Despite the significant progress made in the research, persisting challenges still exist in clinical implementation. Key challenges remain:

  • Need for broader evidence: Large-scale, multicenter transfusion trials across East/Southeast Asia are critical, as current data derive from limited sample size studies.
  • Auto-anti-D observations: Rare cases of auto-anti-D post-exposure (transfusion/pregnancy) have been observed in Chinese carriers8, while one Japanese case exhibited allo-anti-D-like antibodies9.

There are still several critical open questions included:

  • Mechanism (e.g., similarity to auto-anti-D production in weak D types 1, 210, or 1511?).
  • Incidence, persistence and evanescence pattern, and clinical significance of such antibodies.
  • Management of transfusion in carriers with detectable auto-anti-D. Addressing these gaps will strengthen evidence for global adoption of D+ RBC transfusion in Asian-type DEL patients and RhIG exemption in Asian-type DEL pregnant women.

Finally, the management of Asian-type DEL Donors is another important issue. There are two concerns arise regarding Asian-type DEL blood:

1) Transfusion risk: While Asian-type DEL RBCs can (rarely) induce alloanti-D in true D– recipients (< 10 reported cases)12, prospective studies are needed to quantify this risk.

2) Blood supply implications: If we labeling DEL as D+ just like adopted in Europe, the US, and Brazil, this eliminates alloanti-D risk but would reduce already scarce D– supplies in East/Southeast Asia (where D– prevalence is 3–5‰), cutting availability by ~25%. There was some balanced strategies. Some Asian regions label DEL units distinctly, restricting their use for:

  • Women of childbearing age;
  • Alloanti-D-sensitized recipients;
  • Multi-transfusion patients.

For other true D– recipients, DEL RBCs are permitted. This is a pragmatic compromise. Regional policies should weigh transfusion safety against blood supply sustainability. In summary, translating Asian-type DEL research into practice can simplify clinical management: D+ RBC transfusion and RhIG exemption are viable for Asian-type DEL carriers. Collaborative efforts to resolve outstanding questions will optimize guidelines, ensuring global applicability while safeguarding blood resources.

References

  1. Shao CP. Transfusion of RhD-positive blood in "Asia type" DEL recipients. N Engl J Med. 2010;362:472-3.
  2. Flegel WA, Wagner FF. DEL. Blood Transfus. 2020;18:159-62.
  3. Yin Q, Flegel WA. DEL in China: the D antigen among serologic RhD-negative individuals. J Transl Med. 2021;19:439.
  4. Flegel WA. Response to: are weak D RBCs really immunogenic? Transfusion. 2006;46:1063-4.
  5. Park JY, Cho D, Choi HW, Jeon MJ, Park MS, JW S, et al. A patient with RhDel (1227G>A) failed to produce detectable anti-D after transfusion of RhD positive red blood cells. Korean J Blood Transfus. 2006;17:153-8.
  6. Choi S, Chun S, Seo JY, Yang JH, Cho D. Planned Transfusion of D-Positive Blood Components in an Asia Type DEL Patient: Proposed Modification of the Korean National Guidelines for Blood Transfusion. Ann Lab Med. 2019;39:102-4.
  7. Ji Y, Luo Y, Wen J, Sun Y, Jia S, Ou C, et al. Patients with Asian-type DEL can safely be transfused with RhD-positive blood. Blood. 2023;141:2141-50.
  8. Ji Y, Jia S, Chen J, Wen J. Identification of autoanti-D both in Asian-type DEL patients post D+ red blood cell transfusion and Asian-type DEL women carried D+ fetus. Vox Sanguinis. 2025;120 (S1):375. [Abstract]
  9. Ohto H, Ito S, Srivastava K, Ogiyama Y, Uchikawa M, Nollet KE, et al. Asian-type DEL (RHD*DEL1) with an allo-anti-D: A paradoxical observation in a healthy multiparous woman. Transfusion. 2023;63:1601-11.
  10. Pham BN, Roussel M, Peyrard T, Beolet M, Jan-Lasserre V, Gien D, et al. Anti-D investigations in individuals expressing weak D Type 1 or weak D Type 2: allo- or autoantibodies? Transfusion. 2011;51:2679-85.
  11. Takeuchi-Baba C, Ito S, Kinjo R, Miyagi H, Yasuda H, Ogasawara K, et al. Production of RBC autoantibody mimicking anti-D specificity following transfusion in a patient with weak D Type 15. Transfusion. 2019;59:1190-5.
  12. Sandler SG, Flegel WA. Does transfusion of Asian-type DEL red blood cells to D- recipients cause D alloimmunization? Transfusion. 2019;59:2455-8.
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