ABO and Rh Blood Groups

ABO and Rh Blood Groups

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Blood typing classifies individuals into different blood groups depending on the presence or absence of antigens on the surface of their erythrocytes.

The antigens may be proteins, glycoproteins or glycolipids and there are over 38 blood group systems recognised by the International Society of Blood Transfusion.

The ABO system is the most important in transfusion practice. In the ABO system, patients are grouped based on the presence (or absence) of inherited ABO oligosaccharide antigens on the surface of the patient's erythrocytes, as well as the presence of the opposite ABO-related antibodies within the patient's serum.

This article discusses the ABO and Rh blood group systems and outlines the guidelines for blood product compatibility based on the possible interactions between the patient and the transfused blood product.

The ABO system

ABO antigens

In the ABO system, there are two erythrocyte antigens with four possible combinations.

A person's ABO blood type describes the antigens present on their erythrocytes:

  • Group A erythrocytes have the A antigen
  • Group B erythrocytes have the B antigen
  • Group AB erythrocytes have both the A and B antigens
  • Group O erythrocytes do not have any ABO antigens

ABO antibodies

The ABO system is the only blood group system in which individuals generate antibodies to antigens absent from their erythrocytes without prior exposure to those antigens.

The formation of the IgM ABO antibodies to antigens absent in an individual begins at birth but their levels are typically too low for detection until 3-6 months of age.

  • Group A individuals form anti-B antibodies
  • Group B individuals form anti-A antibodies
  • Group AB individuals do not form ABO antibodies
  • Group O individuals form anti-A, anti-B, and anti-AB antibodies

Remember that group O has no relevant ABO antigens, and creates all relevant ABO antibodies.

ABO Blood Group System

The ABO system follows Mendelian genetics, with the blood group controlled by a single ABO gene on chromosome nine. The A and B alleles are codominant, while the O allele is recessive and non-functional.

Genotypes underlying ABO phenotypes include:

  • Group A: can be IAIA or IAi genotypes
  • Group B: can be IBIB or IBi genotypes
  • Group AB: can only be IAIB genotype
  • Group O: can only be ii genotype

The A and B alleles do not code for the antigens themselves, but glycosyltransferases which add sugars onto a protein precursor on the erythrocyte membrane, forming the antigen.

There are subgroups within the ABO system, caused by inherited mutations to the ABO alleles, and related genes. While ABO genetics means that a child's blood group can be statistically inferred from the genotype or phenotype of their parents, subgroups and rare alleles mean that accuracy is not guaranteed.

An example of a subgroup is the A2 ABO group. Most of these subgroups are not clinically important, though the Bombay phenotype (Oh) occurs when the patient lacks the ABO antigen precursor known as the H antigen, leading to no ABO antigen production. These individuals produce strong anti-H and anti-AB antibodies, meaning that they can only be transfused with other Oh red blood cells.

Rh System

The Rh blood group system is comprised of over 50 different antigens, but the most significant is the D antigen, as it is the most immunogenic. Its presence or absence gives a patient the ‘positive’ or ‘negative’ status in typical transfusion nomenclature.

Like most blood group antibodies, anti-D antibodies are only generated through exposure to the foreign antigen. Thus, people with a Rh-negative blood group will not typically have anti-D antibodies unless previously exposed. However, only approximately 1% of transfusions result in alloimmunisation.

Clinically, pregnant women that are Rh-negative (i.e. do not have the D antigen on their erythrocytes) are at risk of generation of anti-D antibodies, known as sensitisation, if their foetus is Rh-positive. Any crossover of erythrocytes from the foetal circulation to the maternal circulation can cause antibody production in the mother.

Anti-D IgG Antibodies

Anti-D IgG antibodies can cross the placenta during subsequent pregnancies, if the next foetus is also Rh-positive, which can lead to Haemolytic Disease of the Foetus and Newborn (HDFN). To avoid HDFN in subsequent pregnancies, prophylactic anti-D is administered routinely to Rh-negative women during each pregnancy and when a possible sensitising event has occurred, such as abdominal trauma, invasive procedures, or birth.

Anti-D is purified from the donations of D-alloimmunised people and works by shielding the D antigen from the maternal immune system and destroying the foetal erythrocytes without triggering an adaptive immune response.

IgG is the only antibody class that can cross the placenta, with most red cell antibodies being IgG, and the naturally occurring ABO antibodies being IgM. However, some people develop IgG ABO antibodies and these mothers can have pregnancies with HDFN due to ABO incompatibility.

Kell Antigen

The Kell antigen is one of the hundreds of erythrocyte antigens outside of the ABO and Rh systems - it is the next most common red cell antibody after the ABO and Rh systems, making it a common cause of HDFN. An IgG anti-Kell antibody can be generated from exposure to the antigen, which can cause HDFN in future pregnancies as it crosses the placenta.

Blood banks typically have regulations that mean women of childbearing age or younger are not given units containing the Kell antigen to avoid the chance that the patient later develops an anti-Kell antibody. It is typical that emergency O negative units are Kell negative.

Blood Product Compatibility

In most cases, transfusion of a product with an identical ABO and Rh group to the patient is best practice. However, this may not be possible in clinical scenarios with limited blood product stocks, or if the patient's blood group is unknown.

A blood product is compatible if there is no antibody-antigen reaction between the product and the patient's blood, or their immune system. Screening for antibodies is part of the standard group and hold pathology test. Any subsequent crossmatch involves testing the units to ensure there is no agglutination reaction between the patient's blood sample and the blood product to be crossmatched.

Transfusion of an incompatible blood product can cause a haemolytic transfusion reaction in which the antibody-antigen reaction causes the affected cells to be destroyed. This haemolysis could be either intravascular or extravascular, depending on whether the classical complement pathway is activated.

Packed red blood cells (pRBCs) contain erythrocytes and additives, with a negligible amount of plasma retained. Therefore, only the antigens of the product need to be considered when determining compatibility, as antibodies are not present in clinically relevant amounts.

Compatibility of pRBCs

  • O patients can only receive O pRBCs
  • A patients can receive A and O pRBCs
  • B patients can receive B and O pRBCs
  • AB patients can receive AB, A, B, and O pRBCs

It is important to note that individuals naturally develop antibodies to ABO antigens, so it is imperative that the units they receive are ABO compatible in order to avoid a haemolytic transfusion reaction.

Rh is a bit more lenient since Rh-negative persons usually do not build anti-D antibodies unless exposed to the antigen. Therefore, they can receive Rh-positive blood, but only in critical situations, such as a trauma call with low Rh-negative blood supply. This should be avoided if the patient is a pre-menopausal women as it can cause HDFN in any pregnancies.

Patients with red cell antibodies should not receive "emergency release" O negative blood as they may still have a haemolytic transfusion reaction. These patients must communicate with the blood bank to determine the most suitable products for them.

Fresh frozen plasma (FFP)

When it comes to plasma compatibility, the consideration is opposite to that of red cell compatibility as no antigens are being transfused and only red cell antibodies need to be taken into account.

Similarly to how O negative is the universal donor of pRBCs due to its lack of clinically relevant ABO and Rh antigens, AB is the universal donor of FFP due to its lack of anti-A or anti-B.

  • O patients can receive O, A, B, and AB FFP
  • A patients can receive A and AB FFP
  • B patients can receive B and AB FFP
  • AB patients can only receive AB FFP

In cases of limited availability of FFP, it is possible to transfuse a non-ABO compatible unit of FFP if the manufacturer has labelled the unit as containing low titres of the offending antibody.

For FFP compatibility, the Rh blood group is not taken into account since no donor D antigens are present.

The same applies to cryoprecipitate.

Fractionated blood products such as Anti-D and IVIG have had both red cells and antibodies removed, thus blood group compatibility does not need to be considered.

Key points

  • ABO blood groups are based on antigens present on the patient's red blood cells. Patients naturally create ABO antibodies, which limit the types of blood products they can safely receive.
  • The Rh blood group is complex, but it is the presence or absence of the D antigen that makes someone Rh-positive or Rh-negative.
  • O negative is the universal donor of pRBCs due to its lack of clinically relevant ABO and Rh antigens. AB is the universal donor of FFP because it contains no anti-A or anti-B.


Anti-D is a type of Human Immunoglobulin G (IgG). It is used to prevent the mother from developing an immunological response to the RhD antigen if the baby has inherited the RhD antigen from the father. This is a prophylactic immunoglobulin which is given to mothers who are RhD negative. This article will look into the benefits of using Anti-D in pregnancy care.

What is the RhD Antigen?

The RhD antigen is a type of red blood cell antigens that are markers on the surface of red blood cells. It is part of the larger ABO blood groups system. There are four major blood groups; A, B, AB and O, determined by the presence or absence of antigens. RhD is a type of antigen present on red blood cells. It is only present in people who have the RhD gene.

What is Anti-D?

Anti-D is an immunoglobulin which is given to RhD negative mothers. It is given at 28 weeks of the pregnancy to prevent the mother from developing immunological memory to the baby's RhD antigen. This immunoglobulin can also be used after the birth, if the baby is found to be RhD positive.

Why is Anti-D Used?

In RhD negative mothers, the development of immunological memory to the baby's RhD antigen can cause complications in future pregnancies. This is known as Hemolytic Disease of the Fetus and Newborn (HDFN). The development of antibodies can cause an immunological attack on the fetus's red blood cells. Anti-D is used to prevent this from happening.


  • National Blood Authority. Guideline for the prophylactic use of Rh D immunoglobulin in pregnancy care. Published in 2021. Available from: LINK
  • Brinc D, Lazarus AH. Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn. Published in 2009. Available from: LINK
  • Strobel E. Hemolytic transfusion reactions. Published in 2008. Available from: LINK
  • Australian Red Cross Lifeblood. Red cells. Published in 2021. Available from: LINK
  • Australian Red Cross Lifeblood. Component compatibility. Published in 2021. Available from: LINK

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