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

Key points

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


Anti-Kpa is an antibody directed to an antigen of the Kell blood group system. The Kell antigens are located on the red blood cell transmembrane glycoprotein known as CD238, and consist of a large group of 35 antigens. Some of these antigens are highly immunogenic, and after the ABO and Rh blood group systems, they are the most common immunogenic group for red blood cells. However, Anti-Kpa itself is extremely rare.

Anti-Kpa was first identified in 1957, named “K” after Kell group (after “Kelleher”, the first producer of an anti-K antibody) and “p” after the name of the first identified anti-Kpa producer, “Penny”. The numerical nomenclature of Kpa is denoted as KEL3. It is part of a triplet of antithetical antigens (Kpa, Kpb and Kpc). Anti-Kpa may be naturally occurring (i.e. arising without stimulus by transfusion or pregnancy related red blood cell exposure), but is more likely to be an alloimmune stimulated antibody. As such, it is usually an IgG antibody, predominantly, IgG1.

Patient management: pre-transfusion and prenatal testing

In the context of transfusion, an anti-Kpa is rarely clinically significant for most patients due to the relative rarity of the Kpa antigen, estimated at only 2% of the Caucasian population. It is not present in people of African or Japanese ancestry. Unlike many other Kell antibodies, when anti-Kpa is detected in a patient’s pre-transfusion sample testing, there is usually no requirement to select Kpa- negative donor red blood cells, given the low incidence of Kpa. Instead, red blood cell units that are serological crossmatch compatible (at 37°C IAT phase) should be selected for transfusion. Routine donor antigen typing (phenotyping) at Canadian Blood Services does not include Kpa typing, therefore a request for Kpa negative red blood cell units results in additional manual phenotyping or genotyping.

If implicated, anti-Kpa may cause mild-to-moderate transfusion reactions, including delayed hemolytic reactions. As it is expressed on umbilical cord red blood cells, it is associated with mild-to-severe hemolytic disease of the fetus and newborn (HDFN). There are only a small number of case reports in which anti-Kpa has been implicated in a severe reaction.  See Table 1 for a summary of recommendations for red blood cell transfusion in patients with non-ABO antibodies.

Anti-Kpa in perinatal samples

Most guidelines recommend that any antibody to a Kell system antigen (including anti-Kpa) should be worked up and monitored in the same manner as an anti-K. Traditionally, it has been thought that the severity of HDFN does not correlate with the titre of anti-K and the current Canadian practice is in keeping with this thought. Detection of any Kell system antibody in a perinatal sample is regarded as a critical titre and these patients are all referred to a maternal fetal medicine specialist right away for increased surveillance of fetal anemia. As such, there is no utility to monitor titres because the patient is already receiving a higher level of care. There is some debate about whether or not Kell antibodies should have serial titration as is done with other red cell alloantibodies in pregnancy. A more recent case series have shown that it may require an anti-K titre of at least 1:32 to cause severe HDFN, however there is not yet enough evidence to change practice in Canada. Given the paucity of cases implicating anti-Kpa, it is likely that future recommendations for handling anti-Kpa will continue to be extrapolated from data around anti-K.

Patients with sickle cell disease

For sickle cell disease patients without antibodies, most guidelines recommend transfusion of Rh- and Kell(KEL1)-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, K, Kidd and Duffy blood group systems along with the S/s antigens. If a patient with sickle cell disease develops an anti-Kpa, then Kpa-negative units should be provided, along with matching for the full Rh and Kell phenotype. Given the increased risk of hyperhemolysis in patients with sickle cell, 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

Peng S, Meunier D. Kell System: Anti-Kpa [Internet]. Ottawa: Canadian Blood Services; 2019 Oct 9 [cited YYY MM DD]. Available from:


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