Transfusion medicine
Red blood cell antigens
ABO / H group

Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.

Topic Completed: 5 April 2021

Minor changes: 5 April 2021

Copyright: 2020-2021, PathologyOutlines.com, Inc.

PubMed Search: ABO / H group "free full text"[SB]

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
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Cite this page: Adkins BD, Booth GS. ABO / H group. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedabohgroup.html. Accessed April 19th, 2021.
Definition / general
  • Most clinically important blood group
  • Incompatible red blood cell transfusion causes intravascular, complement mediated hemolysis
  • Originally described by Landsteiner (AABB: Technical Manual, 19th Edition, 2017)
  • Antibodies are clinically significant
Essential features
  • Patient’s blood type is based on their ABO phenotype
  • Patients naturally form ABO antibodies or isohemagglutinins due to exposure to bacterial moieties mimicking ABO antigens
  • Type O individuals have the H antigen which is unmodified and the blood group system may be referred to as ABH or ABO
  • Anti-ABH antibodies are mostly IgM with a smaller component of IgG but can cause hemolysis and hemolytic disease of the fetus and newborn (HDFN)
  • There are A and B subgroups, which may be recognized due to weaker expression of these antigens or unexpected reactivity (e.g., anti-A1 antibodies in A2 subgroup individuals) (AABB: Technical Manual, 19th Edition, 2017)
  • Some individuals may lack H on red cells or in secretions and develop antibodies (i.e. Bombay or Parabombay patients) (AABB: Technical Manual, 19th Edition, 2017)
Antigens
  • Type: carbohydrate
    • H antigen produced by galactoside 2-alpha-L-fucosyltransferase 1 (FUT1) on red cells and alpha-1, 2-L- fucosyltransferase (FUT2) in secretions; the amount of H varies based on ABO subtype as follows: O > A2 > B > A2B > A1 > A1B (AABB: Technical Manual, 19th Edition, 2017)
    • A antigen is a modification of the H antigen N-Acetylgalactosamine added to the terminal end
      • There are various A subgroups based on the amount of A antigen present on red cells
      • A1 subgroup is associated with the most A antigen on the surface of red cells with A2 being the second most common and having relatively less A antigen and more H antigen
      • A2 patients and A2B patients may occasionally form anti-A1 antibodies which are rarely clinically significant
      • Reference: AABB: Technical Manual, 19th Edition, 2017
    • B antigen is a modification of the H antigen D-galactose added to the terminal end
    • Individuals are type O due to an unmodified H antigen and have a higher proportion of H on the red cell surface (see above)
    • Most common blood groups are as follows in descending order: O, A, B, AB

      Race / Ethnicity
      O
      A
      B
      AB
      White non-Hispanic 45.2% 39.7% 10.9% 4.1%
      Hispanic 56.5% 31.1%   9.9% 2.5%
      Black non-Hispanic 50.2% 25.8% 19.7% 4.3%
      Asian 39.8% 27.8% 25.4% 7.1%
      Native American 54.6% 35%   7.9% 2.5%
      All donors 46.6% 37.1% 12.2% 4.1%


  • Adapted from: Transfusion 2004;44:703
Antibodies
  • Majority IgM, some IgG, anti-A,B, IgG in type O individuals (AABB: Technical Manual, 19th Edition, 2017)
  • Can cause hemolytic reactions and hemolytic disease of the fetus and newborn
    • This is the most common cause of hemolytic disease of the fetus and newborn; occurs most commonly in O mothers with A or B infants via anti-A,B antibodies
    • Hemolytic disease of the fetus and newborn can occur in the first pregnancy, as no sensitizing pregnancy must occur; it develops with IgG antibodies crossing the placenta and generally causes mild anemia
  • Naturally occurring at 3 - 6 months; also known as isohemagglutinins
    • Newborns characteristically lack intrinsic ABO antibodies
Terminology
  • Isohemagglutinins - ABO antibodies
  • Alpha-1, 2-L- fucosyltransferase (FUT2) - also known as the secretor gene that produces H antigen present in secretions
Pathophysiology
  • Bombay phenotype occurs when patients lack H antigen and naturally form anti-H antibodies
  • This is an autosomal recessive condition where patients lack galactoside 2-alpha-L-fucosyltransferase 1 (FUT1)
  • Patients will type as an O individual (denoted as Oh) but will characteristically have a panagglutinin on screening and panel cells
  • Para-Bombay patients lack FUT1 but have a functional FUT2 gene that will produce H in secretions but can still develop anti-H antibodies and should functionally be treated like a Bombay patient
  • Some proteins are posttranslationally modified by ABO antigens such as von Willebrand Factor, which is stabilized with the addition of A or B antigens; likewise, ABO antigens are occasionally implicated in the pathogenesis of certain infectious diseases
    • However, the full scope of the ABO antigens' physiologic functions is not yet determined
Clinical features
Laboratory
  • ABO typing
  • Forward type is based on reagents reacting with ABO antigens on patient red cells
  • Back type is based on patient plasma reacting with ABO antigens on reagent red cells
  • Typing discrepancies can occur and must be interrogated prior to transfusion
  • Reference: Dean: Blood Groups and Red Cell Antigens [Accessed 07 October 2020]

    Blood Group
    Antigens
    Antibodies
    Genotype
    A A Anti-B AA or AO
    B B Anti-A BB or BO
    AB A and B None AB
    O None Anti-A, Anti-B and Anti-A,B OO
Case reports
Board review style question #1
A 27 year old mother of 3 delivers a baby boy at 39 weeks. The mother is O- and the son is A+. The mother received all routine shots and has been followed by OBGYN during all of her pregnancies. She has no history of transfusion. On day 2 of life the son is found to be listless with visible jaundice. Which of the following is the most likely cause of hemolytic disease of the fetus and newborn in this patient?

  1. Anti-D antibodies
  2. Anti-Jka antibodies
  3. Anti-K1 antibodies
  4. Anti-M antibodies
  5. Isohemagglutinins
Board review style answer #1
E. Isohemagglutinins. IgG ABO antibodies are the most common cause of hemolytic disease of the fetus and newborn. This generally occurs in type O mothers with type A babies.

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Reference: ABO / H group
Board review style question #2
A 36 year old man is rushed to the hospital by helicopter after a logging accident. While in flight, the patient receives a unit of O negative red blood cells. Upon arrival the patient is in disseminated intravascular coagulation and laboratory assessment is consistent with hemolysis. He expires and no autopsy is performed; however, a sample in the blood bank typed as O was shown to have anti-H antibodies. Which enzyme or type of enzyme was this patient missing?

  1. ADAMTS13
  2. Amylase
  3. Fucosyltransferase
  4. G6PD
Board review style answer #2
C. Fucosyltransferase. This patient lacks the ability to make the H antigen and has the so called Bombay phenotype.

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Reference: ABO / H group
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