Blood Groups: ABO, Rh and Rare Blood Types
Most people know their blood group as something like A positive or O negative. That description is clinically important, but it only tells you about two blood group systems: ABO and RhD.
Red blood cells carry many inherited surface molecules. In transfusion medicine these are called blood group antigens. The International Society of Blood Transfusion now recognises 49 blood group systems and around 400 red-cell antigens, so two people who are both A positive can still have very different antigen profiles.
Those differences usually cause no problem while the red cells remain in the person who made them. They become important when red cells move between people through transfusion, or when fetal red cells enter the maternal circulation during pregnancy. The recipient's immune system may recognise an unfamiliar antigen and produce an antibody against it.
That is the biological basis of blood-group compatibility.
ABO begins with A, B and H antigens
The ABO system divides people into four main groups: A, B, AB and O. These groups are determined by carbohydrate structures on the red-cell surface.
A precursor called the H antigen is normally present on red cells. The ABO gene encodes enzymes that modify this H structure. A-type enzyme adds the A-specific sugar, B-type enzyme adds the B-specific sugar, and people with group AB express both active forms. The common group O allele does not produce a functional A- or B-adding enzyme, so much of the H antigen remains unmodified.
| ABO group | Antigens on red cells | Expected ABO antibodies in plasma |
|---|---|---|
| A | A | Anti-B |
| B | B | Anti-A |
| AB | A and B | Neither anti-A nor anti-B |
| O | No A or B antigen | Anti-A and anti-B |
The antibody side of the system is what makes ABO incompatibility dangerous. People develop anti-A or anti-B antibodies against the ABO antigen they do not possess. These antibodies are present without a previous transfusion, which is different from most clinically significant red-cell antibodies.
If donor red cells carry an ABO antigen against which the recipient already has antibody, the antibody can bind rapidly to the transfused cells. Complement activation may then cause severe intravascular haemolysis. This is why an ABO-incompatible red-cell transfusion can become life-threatening very quickly.
The safest way to understand ABO compatibility is to think about the donor red-cell antigen and the recipient's antibody. A group B patient has anti-A in their plasma, so group A red cells would be incompatible. A group AB patient has neither anti-A nor anti-B and can therefore receive red cells from any ABO group, provided the rest of the compatibility testing is satisfactory.
The positive or negative part comes from RhD
The plus or minus sign usually refers to the D antigen in the Rh blood group system.
If red cells express D, the person is described as RhD positive. If D is absent, they are RhD negative. The Rh system is much larger than D alone and includes other important antigens such as C, c, E and e.
This important because someone who is RhD negative has not lost the whole Rh system. They lack D but still express a combination of other Rh antigens.
Anti-D is also different from the usual ABO antibodies. A person who is RhD negative does not normally have anti-D simply because they lack the antigen. Anti-D usually develops after exposure to RhD-positive red cells, most commonly through transfusion or pregnancy.
During pregnancy, small numbers of fetal red cells can enter the maternal circulation. If an RhD-negative pregnant person is exposed to RhD-positive fetal cells, sensitisation can lead to immune anti-D. In a later RhD-positive pregnancy, IgG anti-D can cross the placenta and destroy fetal red cells, causing haemolytic disease of the fetus and newborn.
Anti-D immunoglobulin is used to reduce the chance of sensitisation in eligible RhD-negative pregnancies. The exact timing and pathway are governed by national and local maternity guidance.
Combining ABO and RhD gives the eight blood types most people recognise: O positive, O negative, A positive, A negative, B positive, B negative, AB positive and AB negative. Among NHS Blood and Transplant donors, O positive is the most common and AB negative the least common of these eight groups.
Red-cell compatibility is more than matching the same label
For routine transfusion, a patient is usually given red cells of the same ABO and RhD group when suitable units are available. Other ABO-compatible combinations can also be used.
| Recipient | ABO/RhD-compatible red cells |
|---|---|
| O negative | O negative |
| O positive | O positive or O negative |
| A negative | A negative or O negative |
| A positive | A positive, A negative, O positive or O negative |
| B negative | B negative or O negative |
| B positive | B positive, B negative, O positive or O negative |
| AB negative | AB negative, A negative, B negative or O negative |
| AB positive | All eight ABO/RhD groups |
This is a simplified red-cell compatibility framework. It does not replace laboratory compatibility testing because a patient may also have antibodies against antigens in the Kell, Kidd, Duffy, MNS or other systems.
O-negative red cells lack A, B and D antigens, which is why they are particularly useful when red cells are needed before a patient's blood group is known. They are often described as universal red cells in basic teaching.
That phrase has limits. O-negative cells still carry many other blood-group antigens, so they are not automatically compatible with every patient who has clinically significant non-ABO antibodies. In major haemorrhage, local protocols may also use O-positive emergency red cells for selected patients to conserve O-negative stocks.
Plasma compatibility works differently because the important ABO antibodies are in the donor plasma rather than on the donor red cells. This is why “universal donor” statements should always specify which blood component is being discussed.
The laboratory checks for antibodies beyond ABO and RhD
Before most planned red-cell transfusions, the laboratory determines the patient's ABO and RhD group and performs an antibody screen.
The antibody screen is looking for clinically significant antibodies against red-cell antigens other than A and B. If one is detected, further testing identifies its specificity and donor units are selected that lack the corresponding antigen.
For example, a patient may be A positive but also have anti-K against the K antigen in the Kell system. An A-positive unit that carries K could therefore be unsuitable. The laboratory would select ABO-compatible, K-negative red cells.
This is why a historical antibody remains important even if it is no longer detectable on today's screening test. Some red-cell antibodies can fall below routine detection over time but reappear rapidly after re-exposure to the antigen.
Pregnancy and previous transfusion are common routes of alloimmunisation, where the immune system forms an antibody against a red-cell antigen that the person does not have.
Crossmatching then provides another compatibility check before appropriate units are issued. The complexity is handled by the transfusion laboratory, but the process still depends on the sample belonging to the correct patient. Identification errors at sampling can defeat every sophisticated test that follows.
ABO and RhD are only the beginning
Blood-group systems are genetically distinct groups of red-cell antigens. Some of the systems encountered regularly in transfusion medicine include Kell, Kidd, Duffy and MNS, as well as the wider Rh system.
These antigens are not decorative markers. Many are proteins or carbohydrate structures with normal biological roles in the red-cell membrane. Some act as transporters, receptors, adhesion molecules or enzymes.
Most people never need to know their extended antigen profile. It becomes especially important when someone forms an alloantibody or needs repeated transfusions.
Patients with sickle cell disease, thalassaemia and some transfusion-dependent inherited anaemias may receive many units of red cells over their lifetime. Each transfusion exposes the immune system to donor antigens. If alloantibodies develop, the pool of compatible donor units becomes smaller.
Extended red-cell phenotyping identifies which antigens are present on the patient's cells using serological methods. Genotyping examines the genes that predict blood-group antigen expression and can be particularly useful after recent transfusion, when donor red cells may make serological typing difficult.
NHS Blood and Transplant uses extended blood-group genotyping for people with sickle cell disease, thalassaemia and transfusion-dependent rare inherited anaemias. The aim is to improve matching and reduce the risk of additional alloantibody formation.
The Ro subtype is one important UK example. Ro is an Rh-positive subtype that is more common in people of Black African and Black Caribbean heritage and is particularly valuable for matching some patients with sickle cell disease.
This is why donor diversity matters in transfusion medicine. It is not because ethnicity determines one single blood type. Blood-group antigen frequencies differ between populations, so a more diverse donor pool increases the chance of finding closely matched units for a diverse patient population.
What makes a blood type genuinely rare?
AB negative is the least common of the eight familiar ABO/RhD groups among NHS Blood and Transplant donors, but that is not the same as the technical definition of rare blood.
In UK transfusion practice, a rare blood type is generally one occurring in around 1 in 1,000 people or fewer, or a combination of common antigen-negative features that is itself exceptionally uncommon.
A person can therefore have a very ordinary ABO/RhD label, such as O positive, and still have rare blood because of their extended antigen profile.
NHS Blood and Transplant has highlighted phenotypes such as U negative in the MNS system and Jsb negative in the Kell system as examples of rare blood that may be needed for patients with sickle cell disease. Some patients also need combinations such as Fya-negative and Fyb-negative blood.
When compatible blood cannot be found in routine stock, specialist reference laboratories and rare-donor registries become important. The International Blood Group Reference Laboratory in Bristol maintains the International Rare Donor Panel, which contains donor and frozen-unit information contributed by countries around the world.
Bombay phenotype: why ordinary group O blood can be incompatible
The Bombay phenotype, written Oh, is a particularly useful example because it challenges the idea that group O is simply “no A or B”.
Normal group O red cells still carry H antigen. They simply do not convert it into A or B antigen.
People with the Bombay phenotype lack the H antigen itself because of changes affecting the FUT1 pathway. Without H, normal A and B antigens cannot be expressed on the red-cell surface even if the person carries an A or B ABO allele.
On basic forward ABO typing, the cells can therefore resemble group O. The difference becomes critical because a person with Bombay phenotype can have anti-H as well as anti-A and anti-B.
Ordinary group O red cells contain abundant H antigen and can therefore cause severe haemolysis in a person with Bombay phenotype. Compatible transfusion generally requires Bombay-phenotype red cells.
This is one reason full blood-group investigation uses both red-cell and plasma testing. A result that does not behave as expected should not simply be forced into one of the four familiar ABO boxes.
Rhnull: not the same as RhD negative
Rhnull is another exceptionally rare phenotype. In Rhnull, red cells lack all Rh-system antigens, not only D.
This is very different from ordinary RhD-negative blood. An RhD-negative person still expresses other Rh antigens such as C, c, E or e according to their inherited phenotype. A person with Rhnull lacks the entire Rh antigen complex.
The Rh proteins also contribute to red-cell membrane structure, so Rhnull can be associated with chronic haemolysis, abnormal red-cell morphology and a compensated haemolytic anaemia.
Transfusion becomes particularly difficult if a person with Rhnull develops an antibody against high-prevalence Rh antigens, such as anti-Rh29. Ordinary RhD-negative units are not sufficient because they still carry other Rh antigens. Compatible units may need to come from another Rhnull donor, a frozen rare-blood inventory or an international rare-donor search.
Bombay phenotype and Rhnull attract attention because they have memorable names, but the practical lesson is broader. Rare blood often means that a patient lacks an antigen nearly everybody else has, or lacks an unusual combination of several common antigens. The transfusion challenge comes from the immune response, not from how unusual the ABO label looks.
Summary
The eight familiar blood types come from two systems: ABO and RhD. ABO describes whether red cells express A antigen, B antigen, both or neither. RhD describes whether the D antigen is present.
Transfusion compatibility depends on preventing recipient antibodies from attacking antigens on donor red cells. That is why ABO and RhD matching is important, but they are only the first part of pre-transfusion testing.
Hundreds of other red-cell antigens exist across dozens of blood-group systems. Antibodies to Kell, Kidd, Duffy, MNS and other antigens can make additional matching necessary, particularly after pregnancy or repeated transfusion.
Rare blood is defined by the wider antigen profile rather than by ABO alone. Bombay phenotype lacks H antigen, making ordinary group O red cells potentially dangerous. Rhnull lacks all Rh antigens and can create major transfusion challenges. U-negative, Jsb-negative and other uncommon phenotypes are also clinically important when a patient has antibodies that require highly specific donor blood.
References
International Society of Blood Transfusion (2026) Red Cell Immunogenetics and Blood Group Terminology. Available at: https://www.isbtweb.org/isbt-working-parties/rcibgt.html
International Society of Blood Transfusion (2026) ISBT Blood Group Database. Available at: https://blooddatabase.isbtweb.org/database
NHS Blood and Transplant (2026) Blood types. Available at: https://www.blood.co.uk/why-give-blood/blood-types/
NHS Blood and Transplant (n.d.) Blood group genotyping: frequently asked questions for patients. Available at: https://www.nhsbt.nhs.uk/what-we-do/clinical-and-research/blood-group-genotyping/patients/frequently-asked-questions/
NHS Blood and Transplant (n.d.) International Rare Donor Panel. Available at: https://www.nhsbt.nhs.uk/ibgrl/services/international-rare-donor-panel/
NHS Blood and Transplant (n.d.) Rare blood: the facts. Available at: https://www.blood.co.uk/news-and-campaigns/the-donor/rare-blood-the-facts/
NHS Blood and Transplant (n.d.) Blood donation projects: Ro blood. Available at: https://www.nhsbt.nhs.uk/how-you-can-help/get-involved/community-grants-programme/blood-donation-projects/
NHS (2026) Haemolytic disease of the fetus and newborn (HDFN). Available at: https://www.nhs.uk/conditions/rhesus-disease-hdfn/
Joint United Kingdom Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (2026) Guidelines for the Blood Transfusion Services in the UK: Pre-transfusion testing. Available at: https://www.transfusionguidelines.org/red-book/chapter-13-patient-testing-red-cell-immunohaematology/13-3-pre-transfusion-testing
Scharberg, E.A., Olsen, C. and Bugert, P. (2019) ‘An update on the H blood group system’, Immunohematology, 35(2), pp. 67–68. Available at: https://pubmed.ncbi.nlm.nih.gov/31246492/
Shahverdi, E. and Moghaddam, M. (2026) ‘Rhnull phenotype: molecular basis, serologic features, clinical manifestations, and transfusion challenges: a scoping review of published cases’, Immunohematology, 42(2), pp. 42–47. Available at: https://pubmed.ncbi.nlm.nih.gov/42490342/