CMAJ : Canadian Medical Association Journal
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What constitutes the most cautious approach for a pregnant person with weak D type 4.0?
DOI 10.1503/cmaj.78986 , Volume: 193 , Issue: 24 , Pages: E916-E916
Article Type: letter, Article History

Table of Contents



A recent CMAJ Practice article1 on modern Rhesus (Rh) typing in transfusion and pregnancy and its associated correspondence2 prompted a productive discussion on safe recommendations for pregnant patients with a weak D type 4.0 allele, originally described in 2000.3 The differing approaches1,2 represent the personal views of the respective authors. Based on our review of 20 years’ worth of literature on this specialized topic, we have agreed on the following 5 statements:

    • No published case reports have documented adverse clinical effects, such as hemolysis, among pregnant people with weak D type 4.0 caused by an allo- or auto-anti–D.
    • Similarly, no published case reports have documented adverse clinical effects, such as anemia or jaundice, among fetuses or newborns caused by such a mother’s allo- or auto-anti–D.
    • No published evidence has shown that Rh immunoglobulin (RhIg) is clinically effective in an individual with weak D type 4.0 (e.g., for preventing anti-D formation); RhIg can cause a positive direct antiglobulin test, which does not imply clinical harm.
    • The weak D type 4.0 phenotype may be associated with a proportionately larger number of anti-D than most other weak D types.46 The nature of these antibodies has not been well characterized (i.e., allo- v. auto-antibody). 6 A fraction of all people with a weak D type 4.0 are routinely typed as normal RhD-positive and do not receive RhIg.3,7,8
    • The decision of whether or not to use RhIg or RhD-negative transfusion in such mothers should be based on national guidelines.9 Both approaches have been adopted by expert groups2,6,810 and are considered safe. The decision may still depend on an individual patient’s circumstances. 11 If providers are unsure, consultation with a transfusion medicine physician or perinatal immunohematology reference laboratory is recommended.1,10
Competing interests:: None declared.
Funding:: Willy Albert Flegel is supported by the NIH Clinical Center, Intramural Research Program, ID ZIC CL002128.
Disclaimer:: The views expressed do not necessarily represent the views of the National Institutes of Health, the Department of Health and Human Services, or the U.S. Federal Government.


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Pham   BN , Roussel   M , Gien   D , . Molecular analysis of patients with weak D and serologic analysis of those with anti-D (excluding type 1 and type 2). Immunohematology 2013;29:5562.

Westhoff   CM , Nance   S , Lomas-Francis   C , . Experience with RHD*weak D type 4.0 in the USA. Blood Transfus 2019;17:913.

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Ouchari   M , Srivastava   K , Romdhane   H , . Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia. Transfusion 2018;58:30612.

Flegel   WA , Peyrard   T , Chiaroni   J , . A proposal for a rational transfusion strategy in patients of European and North African descent with weak D type 4.0 and 4.1 phenotypes. Blood Transfus 2019;17:8990.


Flegel   WA , Denomme   GA , Queenan   JT , . It’s time to phase out “serologic weak D phenotype” and resolve D types with RHD genotyping including weak D type 4. Transfusion 2020;60:8559.


Yin   Q , Srivastava   K , Brust   DG , . Transfusion support during childbirth for a woman with anti-U and the RHD*weak D type 4.0 allele. Immunohematology 2021;37:14. is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: constitutes the most cautious approach for a pregnant person with weak D type 4.0?&author=&keyword=&subject=Letters,