Diego System: Anti-Dia

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


Dia is an antigen of the Diego blood group system. The 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.

Dia is a low-frequency antigen, occurring at 0.01% in most populations. Some groups with higher incidence of Dia include South American Indigenous (2–54%), Japanese (12%), North American Chippewa Indigenous (11%), Chinese (5%), Hispanic (1%) and Polish (0.47%) populations.

Dia was first identified in 1955 when it was implicated in a case of hemolytic disease of the fetus and newborn (HDFN). It is named after Mrs. Diego, the first known producer of anti-Dia.

Anti-Dia is typically immune stimulated (i.e. by transfusion or pregnancy-related red blood cell exposure) IgG1 plus IgG3 and is best detected by IAT at 37°C. Only rare examples of naturally occurring anti-Dia have been reported.

Patient management: Pre-transfusion and prenatal testing

In the context of transfusion, anti-Dia may be clinically significant. It has the ability to cause mild to severe HDFN, but there are only infrequent reports of it being clearly implicated in a hemolytic transfusion reaction. Given the general rarity of Dia antigen, for both current and historically detected anti-Dia, red blood cell units that are crossmatch compatible in the IAT phase at 37°C should be selected for transfusion. Routine donor antigen typing (phenotyping) at Canadian Blood Services does not include Dia typing, therefore a request for Dia-negative red blood cell units results in additional manual phenotyping and/or genotyping.  See Table 1 for a summary of recommendations for red blood cell transfusion in patients with non-ABO antibodies.

Patients with 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 sickle cell patient develops an anti-Dia, then Dia-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 LearnSerology.ca, 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-Dia [Internet]. Ottawa: Canadian Blood Services; 2019 Sept 25 [cited YYYY MM DD]. Available from: https://profedu.blood.ca/en/transfusion/best-practices/serological-best-practices


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