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Original Author(s): Neera Chaudhary and Laurie Peters
Last updated: 27th May 2021
Revisions: 5

Original Author(s): Neera Chaudhary and Laurie Peters
Last updated: 27th May 2021
Revisions: 5

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Blood typing is a method of classifying blood into different groups depending on the presence of different antigens on the surface of red blood cells (RBCs). Understanding the different blood groups is vital in preventing complications from blood transfusion.

In this article, we will explore the most common blood grouping systems, blood transfusions, associated investigations, and clinical correlations.

ABO Grouping System

Erythrocytes (RBCs) have multiple glycoprotein antigens attached to their cell surface. The most important are ABO antigens, which determine a person’s ABO blood group. An individual inherits one ABO allele from each parent, with A and B alleles being codominant and producing the A and B antigens respectively.

  • Group A – have A antigens attached to erythrocyte cell surface
  • Group B – have B antigens attached to erythrocyte cell surface
  • Group AB – have both A and B antigens attached to erythrocyte cell surface
  • Group O – have neither antigen attached to erythrocyte cell surface

Each person also has ABO antibodies in their plasma, which will recognise and attack RBCs expressing foreign antigens. These antibodies develop over the first months and years of life. This is crucial in blood transfusion as giving someone an incompatible blood group can be potentially fatal. The A and B antibodies are predominantly IgM.

  • Group A – have anti-B antibodies
  • Group B – have anti-A antibodies
  • Group AB – have neither antibody
  • Group O – have both anti-A and anti-B antibodies

    Figure 1 – Summary of blood types

Rhesus Grouping System

The second most important blood grouping system is based on Rhesus (Rh) antigens. There are many different Rh antigens but only 5 are clinically significant: D, C, c, E, and e.

Rh D is the most immunogenic (i.e. likely to produce an immune response) and therefore the most likely to precipitate a transfusion reaction. The presence or absence of Rh D antigen on erythrocyte cell surfaces determines whether blood is Rhesus positive (Rh+) or Rhesus negative (Rh-).

  • Rh positive: have the Rh D antigen and can receive both Rh+ and Rh- blood
  • Rh negative: lack the Rh D antigen and should only receive Rh- blood

Rh negativity is generally more prevalent in Caucasian populations (15%), than Afro-Caribbean (8%) and Asian (1%) populations but prevalence varies in different parts of the world.

Unlike ABO antibodies, anti-D antibody is usually not present in Rh- people until they have been exposed to Rh+ erythrocytes. Rh- patients should not be transfused with Rh+ blood as this can cause them to develop anti-D antibodies, which may cause transfusion reactions in the future.

Alongside ABO and Rh blood types, there are many blood group systems based on other antigens. These antigens can also, more rarely, cause transfusion reactions.

Clinical Relevance

Blood Transfusion

A person should not receive blood products containing antigens for which they have the corresponding antibodies. Transfusing an incompatible blood type will precipitate a potentially fatal transfusion reaction. Patients having blood transfusions need to be frequently monitored, particularly at the start of each unit.

People with blood type O- are universal donors – they can donate their blood to anyone. This is because their RBCs have no A, B, or RhD antigens which the recipient’s immune system could attack.

People with blood type AB+ are universal recipients – they can receive blood from anyone. This is because their plasma does not contain anti-A, anti-B, or anti-D antibodies, so they will usually not mount an immune response to the donor blood.

Figure 2 – Generic bag of packed red cells, labelled as group B

Haemolytic Disease of the New-born (HDN)

The most severe type of HDN is caused by anti-D antibodies.

Rh D sensitisation occurs when a Rh- person is exposed to the Rh D antigen: typically during a first pregnancy if the foetus is Rh+. The presence of Rh D antigens in the maternal circulation stimulates the production of anti-D antibodies.

Maternal anti-D antibodies recognise and destroy foetal Rh+ RBCs. Upon first exposure, the antibodies are IgM, which cannot cross the placenta and will not cause issues in the first pregnancy.  However, future Rh+ pregnancies will result in the production of large amounts of IgG anti-D which can cross the placenta and cause haemolysis.

Thankfully the administration of anti-D Ig prophylaxis to unsensitised Rh- mothers has significantly reduced the incidence of HDN caused by anti-D antibodies. The prophylaxis works by destroying foetal RBCs that leak into the maternal circulation, reducing the chance of Rh D sensitisation.

Blood typing and Cross-matching

To avoid transfusion of incompatible blood types, blood needs first to be typed (also known as a “group and save”), then cross-matched.

ABO typing tests the patient’s blood for the presence of A/B antigens, and A/B antibodies; this is followed by Rh typing. The lab will also screen the patient’s blood for atypical antibodies.

Cross-matching involves mixing the donor’s blood with the recipient’s blood to detect any immune reaction.

Antiglobulin Testing (Coombs’ Test)

Direct Antiglobulin Testing (DAT) detects whether a patient’s RBCs have antibodies directly attached to them. Coombs’ reagent (which binds specific immunoglobulins) is added to the patient’s blood – a positive test results in the RBCs agglutinating (clumping together).

A positive DAT indicates that haemolysis has an immune aetiology, causes include: autoimmune haemolytic anaemia, haemolytic transfusion reactions, and HDN.

Indirect Antiglobulin Testing (IAT) detects antibodies present in the patient’s plasma. This can be used in cross-matching or to detect maternal anti-D IgG. In IAT, the patient’s isolated plasma is combined with a donor’s RBCs and Coombs’ reagent.

Again, the test is positive if agglutination occurs. This indicates the patient has antibodies against the antigens present on the donor’s RBCs.

Figure 3 – Schematic of the direct and indirect Coombs test