ABO and Rhesus Blood Groups

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Introduction

Blood typing categorises individuals into blood groups based on the presence or absence of antigens on the surface of their erythrocytes.

The antigens may be proteins, glycoproteins, or glycolipids, depending on the blood group system. 

There are over 38 blood group systems as recognised by the International Society of Blood Transfusion, and each is genetically discrete and governed by a single gene, or multiple closely linked genes.1

The ABO system is the most important blood group system 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.1,2

In this article, the ABO and Rhesus (Rh) blood group systems will be outlined, and the guidelines of blood product compatibility will be explained based on the possible interactions between the patient and the transfused blood product.

For more information on transfusion, see the Geeky Medics guide to blood transfusion.


The ABO system

ABO antigens

In the ABO system, there are two erythrocyte antigens of note, with four possible combinations and thus four different ABO blood groups.

A person’s ABO blood type describes the antigens present on their erythrocytes:1,2

  • Group A erythrocytes only have the A antigen
  • Group B erythrocytes only 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.

Other blood group systems require exposure, such as through transfusion of blood products, or in pregnancy.

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.1,2

  • 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 it creates all relevant ABO antibodies.

ABO blood group system
Figure 1. ABO blood group system

ABO genetics

The ABO system follows simple Mendelian genetics, with the blood group controlled by a single ABO gene on chromosome nine.

The ABO alleles do not code for the antigens themselves, but glycosyltransferases which add sugars onto a protein precursor on the erythrocyte membrane, forming the antigen.2

The A and B alleles (IA and IB) are codominant, while the O allele (i) is recessive and non-functional in the ABO system.

Genotypes underlying ABO phenotypes:1,2

  • 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

There are subgroups within the ABO system, caused by inherited mutations to the ABO alleles, and related genes. An example is the A2 ABO group. Most of these subgroups are not clinically important.

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.

For example, 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.1


Rhesus (Rh) system

The Rhesus (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.2 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. While exposure to foreign antigens is typically required for antibody generation (known as alloimmunisation), only approximately 1% of transfusions result in alloimmunisation.2 

Clinical relevance: prophylactic anti-D in pregnancy

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. The anti-D IgG antibodies can then cross the placenta during subsequent pregnancies and, if the next foetus is also Rh-positive, can cause haemolytic disease of the foetus and newborn (HDFN).3 

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 such as amniocentesis, or birth.3

Anti-D is purified from the donations from D-alloimmunised people, and is thought to work through a combination of shielding the D antigen from the maternal immune system, and outright destroying the foetal erythrocytes without triggering the adaptive immune response.4

IgG is the only antibody class that can cross the placenta. Most red cell antibodies are IgG, though the naturally occurring ABO antibodies are typically IgM. However, a small number of people develop IgG ABO antibodies, and these mothers can have pregnancies with HDFN due to ABO incompatibility.2


Kell antigen

While there are hundreds of erythrocyte antigens outside of the ABO and Rh systems, the Kell antigen is relevant to clinical practice.

Anti-Kell is the next most common red cell antibody after the ABO and Rh systems, and thus is a common cause of HDFN.2 Generation of an IgG anti-Kell antibody from exposure to the antigen can cause HDFN in future pregnancies as it crosses the placenta. 

For this reason, blood banks typically have rules that stipulate that women of childbearing age or younger are not given Kell positive pRBC (which contain 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, as this limits exposure to foreign antigens and thus decreases the risk of transfusion reactions. 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 clinically or analytically detectable antibody-antigen reaction between the product and the patient’s blood, or their immune system.

In most patients, a compatible unit is one that is ABO and Rh compatible, as these groups tend to be the most immunogenic. However, those that have undergone alloimmunisation will need to be given red cell products that do not contain the matching antigen. 

Screening for antibodies is part of the standard group and hold pathology test (also known as a type and screen). Any subsequent crossmatch involves testing the units to ensure there is no clinically detectable 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, where 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.

The affected cells could be the transfused cells if the patient had an antibody against an antigen present on them, or it could be the patient’s own cells in the case of a plasma transfusion with an ABO incompatibility.5

Packed red blood cells (pRBCs)

pRBCs contain erythrocytes and additives, with a negligible amount of plasma retained.6

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:2

  • 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

Remember that people naturally develop antibodies to the ABO antigens, and thus it is critical that the units they receive are ABO compatible.

Giving a B patient an A group pRBC unit, for example, would likely cause a haemolytic transfusion reaction as the patient’s own anti-A can lyse the transfused cells.

Rh is more flexible as Rh-negative patients typically do not create anti-D antibodies unless exposed to the antigen. If they are not already alloimmunised to D they can be given Rh-positive blood.

However, this is typically reserved for critical situations, such as a trauma call with low Rh-negative blood stock, as the patient can develop anti-D which can affect their ability to receive blood products in the future. If the patient is a pre-menopausal woman, generation of allo-D can also cause HDFN in any future pregnancies. 

Not every patient should receive emergency release O negative blood. Patients with red cell antibodies to antigens present on the emergency release units can still have a haemolytic transfusion reaction. In patients with red cell antibodies, communication with the blood bank is essential to confirm the safest products for the patient.

Fresh frozen plasma (FFP)

Plasma compatibility can be thought of as ‘opposite’ to red cell compatibility. As the transfusion involves plasma, no antigens are being transfused, and only red cell antibodies need to be considered.

Just like O negative is the universal donor of pRBCs because it contains no clinically relevant ABO and Rh antigens, AB is the universal donor of FFP because it contains no 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 some clinical situations with low 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.7

Note that the Rh blood group system does not factor into FFP compatibility as no donor D antigens are present. All donors would be screened for common and clinically relevant red cell antibodies so it can be assumed that the FFP unit does not contain antibodies like anti-D and anti-Kell.

Like FFP, cryoprecipitate contains only donor plasma, so the rules for FFP compatibility can be followed.

Fractionated blood products such as Anti-D and IVIG have had both red cells and antibodies removed, and 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 then limits 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 a patient Rh-positive or Rh-negative.
  • O negative is the universal donor of pRBCs because it contains no clinically relevant ABO and Rh antigens. AB is the universal donor of FFP because it contains no anti-A or anti-B.

Editor

Dr Chris Jefferies


References

  1. Smart E, Armstrong B. Blood group systems. Published in 2020. Available from: [LINK]
  2. Harmening DM. Modern blood banking and transfusion practices. 6th Published in 2012.
  3. National Blood Authority. Guideline for the prophylactic use of Rh D immunoglobulin in pregnancy care. Published in 2021. Available from: [LINK]
  4. 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]
  5. Strobel E. Hemolytic transfusion reactions. Published in 2008. Available from: [LINK]
  6. Australian Red Cross Lifeblood. Red cells. Published in 2021. Available from: [LINK]
  7. Australian Red Cross Lifeblood. Component compatibility. Published in 2021. Available from: [LINK]

Image references

  • Figure 1. OpenStax College. 1913 ABO Blood Groups. Licence [CC BY 3.0] Available from: [LINK]

 

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