Authors: Danielle Meunier, MD; Sophia Peng, MD; and Gwen Clarke, MD, FRCPC
Publication date: September 2019
Primary target audiences: Medical laboratory technologists (MLT) in a hospital laboratory, transfusion medicine physicians

Key points

  • Anti-Wra is clinically significant.
  • Patients with anti-Wra should receive red blood cell units crossmatch compatible by IAT at 37°C for transfusion.
  • Patients with sickle cell disease who have anti-Wra should be provided with Wra-negative red blood cell units for transfusion.


Wra (DI3) is an antigen of the Diego blood group system. The Wright antigens, along with the other Diego antigens, are located on the red blood cell membrane glycoprotein AE1 (also known as Band 3 or CD233), which plays an essential role in cellular gas exchange and anion equilibrium.

The antithetical Wright antigens, Wra and Wrb, differ by one amino acid substitution. Wra is a low-frequency antigen in all ethnic groups, occurring at less than 0.01%, while Wrb is a high-frequency antigen with almost universal expression across all populations.

Anti-Wra was first described in 1953 when it was implicated in a case of hemolytic disease of the fetus and newborn (HDFN). It was later assigned to the Diego blood group system in 1995 and is named after the family in which the antibody was first found.

Anti-Wra often occurs naturally (i.e. arising without stimulus by transfusion or pregnancy-related red blood cell exposure) or can be immune stimulated. It occurs in up to 2% of blood donors, is frequently found in patients with autoimmune hemolytic anemia, and is often found in association with other antibodies. Anti-Wra in healthy donors is predominantly an IgM antibody with or without an associated IgG component. It can also be predominantly IgG, with IgG1 and IgG3 subclasses most commonly identified in pregnant or previously transfused patients.

Patient management:  Pre-transfusion and prenatal testing

In the context of transfusion, anti-Wra is clinically significant. It is associated with acute and delayed hemolytic transfusion reactions, sometimes severe. It is also associated with mild to severe hemolytic disease of the fetus and newborn (HDFN). Nevertheless, anti-Wra is not routinely included on antibody screening cells. Despite the relatively common occurrence of the antibody, the combination of a predominantly IgM antibody—which, for the most part, do not react well at body temperatures— with the rarity of the Wra antigen on donor cells makes the probability of incompatible units extremely low, especially with serological crossmatch. Thus, for both current and historically detected anti-Wra, red blood cell units that are crossmatch compatible in the 37°C IAT phase should be selected for transfusion. Routine donor antigen typing (phenotyping) at Canadian Blood Services does not include Wra typing; therefore, a request for Wra-negative red blood cell units results in additional manual phenotyping.  See Table 1 for a summary of recommendations for red blood cell transfusion in patients with non-ABO antibodies.

Patients and sickle cell disease

For sickle cell disease patients without antibodies, most guidelines recommend transfusion of Rh-and Kell-matched units. For those patients with one or more antibodies (current or historical), complete donor phenotype/genotype matching is often recommended. Typically, this matching includes the Rh, Kell, Kidd and Duffy blood group systems along with the S/s antigens. If a patient with sickle cell disease develops an anti-Wra, then Wra-negative units should be provided, along with matching for the full extended phenotype. Given the increased risk of hyperhemolysis in patients with sickle cell disease, this clinical context necessitates full compatibility with the patient’s antigen and antibody profile.

Table 1: Red blood cell transfusion for patients with non-ABO antibodies

Patient Antibody Recommendation for red blood cell transfusion*
Diego system
Anti-Dia Red blood cell units crossmatch compatible by IAT at 37°C
Anti-Wra Red blood cell units crossmatch compatible by IAT at 37°C
Kell system
Anti-Jsa Jsa-negative red blood cell units crossmatch compatible by IAT at 37°C
Anti-Kpa Red blood cell units crossmatch compatible by IAT at 37°C
Lewis system
Anti-Lea, Anti- Leb, and Anti-Lea Red blood cell units crossmatch compatible by IAT at 37°C
Lutheran system
Anti-Lua Red blood cell units crossmatch compatible by IAT at 37°C
MNS system
Anti-M Red blood cell units crossmatch compatible by IAT or equivalent using IgG antihuman globulin
Rh system
Anti-Cw Red blood cell units crossmatch compatible by IAT at 37°C
Anti-V V-negative red blood cell units crossmatch compatible by IAT at 37°C

* Note: Patients with sickle cell disease who develop any one of the antibodies listed here should be provided with antigen-negative red blood cell units for transfusion.

Additional resources

For an introduction to immunohematology and the foundations of blood bank compatibility testing, visit, an online educational resource developed by transfusion medicine specialists in Canada. The curriculum consists of six modules and includes an interactive module for completing an antibody investigation panel.

Suggested citation

Meunier D, Peng S, Clarke G. Diego System: Anti-Wra [Internet]. Ottawa: Canadian Blood Services; 2019 Sept 25 [cited YYYY MM DD]. Available from:


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