Biomedical Research

Classifying Blood Groups – and the Danger of the Unknown

This article looks at the classification of blood groups in humans based on their biological structure. As well, this article discusses the significance of the discoveries of classification in the medical field, such as by preventing many deaths from blood transfusions as well as of the foetus during pregnancy.

The concept of blood groups is well-known, and there are a total of eight main blood group types (within the ABO group). The four main types are Type O, Type A, Type B and Type AB, and each type can be either positive or negative. The blood type an individual has is determined by the genes they inherit from their parents, and the gene for type O blood is recessive while the genes for types A and B are both dominant. Blood types are categorised based on the antibodies in the plasma and antigens on the cell surface membrane of the erythrocytes. The knowledge of the different blood types plays a vital role in medicine–and one significant reason for this is ensuring blood compatibility for blood transfusions–otherwise this could result in the death of the recipient.

However, beyond the ABO group, there are 34 other blood group systems, and within these systems there are over 300 variants. Examples of such lesser-known and rarer blood group systems are the MNS blood group system and the Duffy Blood Group.

Blood Group ABO

Blood transfusions were common before the discovery of human blood groups in the year 1900, but it was not understood why some were unsuccessful while others were fatal. It was in 1900 that Karl Landsteiner, who was working at the University of Vienna, discovered blood groups through his scientific experimentation1. Karl Landsteiner took blood samples from his staff members and mixed them together, finding in some cases that the erythrocytes would be agglutinated when combined with the blood serum from a separate person. The results of these initial experiments led Karl Landsteiner to conclude that there were three blood types: A, B, and C (which would later be renamed O) and this then became known as the ABO system. The blood group AB was discovered in 1901. In 1930, Karl Landsteiner was awarded the Nobel Prize in physiology and medicine2.

Classifying Blood Groups

Blood types are classified into distinct groups based on the presence and form of antibodies and antigens in the blood. Antigens are structures found on the cell surface membrane of cells, here it is the erythrocytes, and they trigger an immune response. As part of this immune response, antibodies are produced by lymphocytes, and they bind to specific antigens. Some forms of antibodies attack the antigens by disabling processes in the cells which they are attached to, while others cause the foreign cells to clump together – and so facilitate the eradication of them, for example, by phagocytosis.

A person with blood type A will have Anti-B antibodies in their blood plasma, and A antigens. A person with blood type B will have Anti-A antibodies in their blood plasma, and B antigens. A person with blood type AB will have both A and B antigens but will not have any antibodies in their blood plasma. On the other hand, a person with blood type O will have both Anti-A and Anti-B antibodies in their blood plasma, but no antigens on their erythrocytes. Due to the presence of these antibodies and antigens, not all blood types are compatible with one another. For instance, if a person with blood type B received a blood transfusion where the donor has blood type A, the Anti-B antibodies in the recipient’s plasma will attack the erythrocytes from the donor blood. This will cause the erythrocytes to clump together, leading to clots and ultimately culminating in the death of the recipient.

Blood type AB is considered to be the universal recipient due to the absence of antibodies in the plasma of individuals with this blood type. Thus, when donor blood enters the circulatory system, antibodies will not attack the erythrocytes. Inversely, blood type O is considered to be the universal donor, as there are no antigens to be recognised nor stimulate an immune response3.

However, the rules of blood compatibility also depend on whether the individual has a positive or negative blood type. Whether an individual has a positive or negative blood group type is determined by the presence of the rhesus protein – named after the rhesus monkey, which also carries genes to code for this specific protein4. The rhesus protein is otherwise known as the D antigen or the Rh factor, and an absence of Rh antigens means that a person is Rh negative while the presence of such antigens makes a person Rh positive. Just as blood ABO group is inherited from parents, the positive or negative Rh factors are also genetically inherited. For an individual to have a Rh-negative blood type, both of their parents must have at least one negative Rh factor each in their genetic material. Therefore, a Rh-negative blood group is less common than a Rh-positive blood group, as a person has to have at least one negative Rh factor to have Rh negative blood themselves4.

Rh Protein and Pregnancy

A Rh-positive individual is able to receive blood from an Rh positive or Rh-negative donor, but a Rh-negative person is only able to receive Rh negative blood. This presents a problem during pregnancy and delivery when the mother and the foetus may be opposing Rh groups. For example, the mother is Rh negative, but the foetus is Rh positive, and if the mother is exposed to the foetus’s blood during birthing (or at any point during the pregnancy) then this can have fatal consequences. The result of this would be that the mother’s body would be stimulated to produce antibodies to the Rh antigens. If the mother had subsequent pregnancies, these antibodies her body has produced would attack the erythrocytes of the foetus’s should they also have Rh positive blood. This can be done as the mother’s antibodies can cross the placenta and reach the foetus, where they attack its erythrocytes. This leads to a condition called ‘haemolytic disease of the new-born’ (HDN) and can cause anaemia, seizures, jaundice, brain damage or potentially even kill the foetus5.

The difficulties of Rh groups of the mother and foetus during pregnancy and delivery – as well as later pregnancies – are greatly reduced. This is done through injecting the (Rh negative) pregnant woman with Rh antibodies, which eliminates the immune response in the mother that the Rh antigens from the foetus’s blood could potentially trigger. These antibodies are injected into the pregnant woman as ‘RhoGam’, which was only approved by the FDA in 1968. RhoGam is only given if the pregnant mother is Rh negative, but her foetus is Rh positive, and this injection is typically given at an early stage in the third trimester of the pregnancy. The mother can also receive a second RhoGam injection within 72 hours of giving birth.

Before the development and use of RhoGam, HDN affected approximately 1% of all new-born infants and led to the death of 1 out of every 2200 births6, according to an article entitled ‘Management of pregnancies with RhD alloimmunisation”. Also, in this article is stated that “in England and Wales, about 500 foetuses develop haemolytic disease each year, and about 25-30 babies die from haemolytic disease of the new-born”.

MNS and Duffy Blood Groups:

The MNS blood group is categorised by the presence of MNS antigens, which are carried by glycophorin proteins and are located on the cell surface membrane of erythrocytes. MNS antigens are carried by the glycophorins A and B, which can also be receptors for pathogens such as plasmodium falciparum, one of the deadliest malarial parasites. The MSN blood group was discovered shortly after the ABO blood group, in 1927, and the M and N antigens were identified then. It took approximately 20 years for the S and s antigens to be detected. While the M, N, S, and s antigens are the most frequently occurring within the MSN blood group, there are more than 40 other antigens7.

Like the glycoproteins for the MSN antigens, the Duffy glycoprotein is also a receptor for Plasmodium vivax – another malarial parasite8. This means that individuals lacking the Duffy antigens could potentially be immune to this strain of malaria, as the Plasmodium vivax parasites would not be able to connect to the Duffy antigens if they are absent. As well, the Duffy glycoprotein is a receptor for chemicals which cells secrete as the result of inflammation. The Duffy blood group is a blood type classification determined by the presence of the Duffy glycoprotein, otherwise known as Fy antigens, on the cell surface membranes of erythrocytes. Fy antigens can also be located on endothelial cells, epithelial cells in the alveoli and in the collecting ducts in nephrons. The four possible Fy phenotypes are: Fya+b+, Fya+b-, Fya-b+, and Fya-b-, and the first Duffy antigen discovered was Fya, in the year 19509.


While the general knowledge of blood groups is well known by most, there are many more blood types and variants within these groups that are newly discovered and less-commonly known about. Despite the fact that the ABO blood group system is at least 20 million years old, and has mutated and been inherited since its development, it remains a scientific mystery as to why exactly humans (and other primates) have distinct blood types in the first place. It is hypothesised that the frequency and distribution of blood types worldwide is linked to where diseases/infectious organisms are endemic. For instance, an article titled “Why do people have different blood types?”10 written by Harvey G. Klein (Chief of the Department of Transfusion Medicine for the National Institutes of Health) comments that people with blood type A are more susceptible to smallpox. Klein notes the correlation between this and the fact that there is a higher frequency of blood type B across China, India, and Russia – where there were prolific epidemics of smallpox in the past. The full extent of why a variety of blood groups exist remains unknown but linking it to evolution and global distribution of both people and pathogens seems an auspicious theory.

Samara Macrae, Youth Medical Journal 2022


1.   US National Library of Medicine National Institutes of Health: “A Brief History of Human Blood Groups” –,is%20given%20in%20Table%202.

2.   National Library of Medicine: “A brief history of human blood groups” –

3.   Smithsonian Magazine: “The Mystery of Human Blood Types” –

4.   Carter BloodCare Blog: “The Significance of Being Rh Negative or Rh Positive” –

5.   Dallas Obgyn PA: “RhoGam: The triumph of medical science over Rh disease” –

6.   US National Library of Medicine National Institutes of Health: “Management of pregnancies with RhD alloimmunisation” –

7.   NCBI: “The MNS blood group” –

8.   NCBI: “The Duffy blood group” –

9.   Britannica: “Duffy blood group system” –

10.   Scientific American: “Why do people have different blood types?” –


By Samara Macrae

Samara MacRae is a student at Brighton College, England. She hopes to pursue medicine in the future, and is especially interested in surgery and emergency medicine.

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