Blood type

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A blood type (or blood group) is a characteristic of an individual's red blood cells, defined in terms of specific substances (carbohydrates and proteins) on the cell membrane. All species have their own blood types; however, for the most part, these have not been studied to any significant degree. This article focuses primarily on blood types in humans.

The two most important classifications to describe blood types in humans are ABO and the Rhesus factor (Rh factor). There are 46 other known antigens in humans, most of which are much rarer than ABO and Rh. Blood transfusions from incompatible groups can cause an immunological transfusion reaction, resulting in hemolytic anemia, renal failure, shock, and death. The ABO blood types also exist among chimpanzees and bonobos.

The phrases "blood group" and "blood type" are often used interchangeably, although this is not technically correct. "Blood group" is used to refer specificially to a person's ABO status, while "blood type" refers to both ABO and Rh factors.

Principles

Blood type is determined by the antigens (epitopes) on the surface of a red blood cell. Some of these are proteins, while others are proteins with polysaccharides attached. The absence of some of these markers leads to production of antibodies against this marker. The exact reason why this happens is poorly understood, as generally an antigen needs to be present to elicit an immune response. Administration of the wrong blood type would lead to immediate destruction of the infused blood. The breakdown products cause acute medical illness; hence, it is of, quite literally, vital importance that the blood types of the donor and receptor are properly matched.

Austrian scientist Karl Landsteiner is widely credited with the discovery of the main blood type system (ABO) in 1901; he was awarded the Nobel Prize in Physiology or Medicine in 1930 for his work. Subsequently it was found that Czech serologist Jan Janský had independently pioneered the classification of human blood into four groups in 1907, but Landsteiner's independent discovery had been accepted by virtually the whole scientific world while Janský remained in relative obscurity. Landsteiner described A, B, and O; Decastrello and Sturli discovered the fourth type, AB, in 1907. Landsteiner and Alexander S. Wiener also discovered the second most important antigen set, the Rhesus system, in 1937 (publishing in 1940).

ABO system

Humans have the following blood types along with their respective antigens and antibodies:

  • Individuals with type A blood have red blood cells with antigen A on their surface, and produce antibodies against antigen B in their blood serum. Therefore an A-negative person can only receive blood from another A-negative person or from an O-negative person.
  • Individuals with type B blood have the opposite arrangement: antigen B is on their cells, and antibodies against antigen A are produced in their serum. Therefore, a B-negative person can only receive blood from another B-negative person or from an O-negative person.
  • Individuals with type AB blood have red blood cells with both antigens A and B, and do not produce antibodies against either antigen in their serum. Therefore, a person with type AB-positive blood can safely receive any ABO type blood and is called a "universal receiver". However an AB-positive person cannot donate blood except to another AB-positive person.
  • Individuals with type O blood have red blood cells with neither antigen, but produce antibodies against both types of antigens. Therefore, a person with type O-negative blood can safely donate to a person with any ABO blood type and is called a "universal donor". However, an O-negative person can only receive blood from another O-negative person.

Overall, the O blood type is the most common blood type in the world, although in some areas, such as Sweden and Norway, the A group dominates. The A antigen is overall more common than the B antigen. Since the AB blood type requires the presence of both A and B antigens, the AB blood type is the rarest of the ABO blood types. There are known racial and geographic distributions of the ABO blood types. [1] According to [Benes93] it can be partly attributed to the relation among blood types and particular illnesses: apparently, certain blood types give greater (or lesser) resistance to various diseases. For instance, type-O people have lessened resistance to the Black Plague, and therefore type O is less common in European populations.

The precise reason why people develop antibodies against an antigen they have never been exposed to is unknown. It is believed that some bacterial antigens are similar enough to the A and B glycoproteins, and that antibodies created against the bacteria will react to ABO-incompatible blood cells.

Apart from red blood cells, the ABO antigen is also expressed on the glycoprotein von Willebrand factor (vWF), which participates in hemostasis (control of bleeding). In fact, blood type O predisposes very slightly to bleeding, as vWF is degraded more rapidly. ABO antigens are also present in many other tissues such as liver, kidneys and lungs.

The H antigen

The A & B antigens are derived from a common precursor known as the H antigen. The H antigen is a glycosphingolipid (sphingolipid with carbohydrates bonded to the ceramide moiety) which is modified to produce the A and B antigens. In type O blood, it remains unchanged and consists of a chain of galactose, N-acetylglucosamine, galactose, and fructose attached to the ceramide. Since it lacks N-acetylneuraminic acid (sialic acid) it is referred to as a globoside, not a ganglioside. Type A has an extra N-acetyl galactosamine bonded to the galactose near the end, while type B has a third galactose bonded to that near-end galactose.

Inheritance

Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene with three alleles: i, IA, and IB. The gene encodes a glycosyltransferase - that is, an enzyme that modifies the carbohydrate content of the red blood cell antigens. The gene is located on the long arm of the ninth chromosome (9q34).

IA allele gives type A, IB gives type B, and i gives type O. IA and IB are dominant over i, so ii people have type O, IAIA or IAi have A, and IBIB or IBi have type B. IAIB people have both phenotypes because A and B express a special dominance relationship: codominance, which means that type A and B parents can have an AB child. Thus, it is extremely unlikely for a type AB parent to have a type O child (it is not, however, direct proof of illegitimacy).

Evolutionary biologists theorize that the IA allele evolved earliest, followed by O (by the deletion of a single nucleotide, shifting the reading frame) and then IB. This chronology accounts for the percentage of people worldwide with each blood type. It is consistent with the accepted patterns of early population movements and varying prevalent blood types in different parts of the world: for instance, B is very common in populations of Asian descent, but rare in ones of Western European descent.)

Blood group inheritance
Mother/Father O A B AB
O O O, A O, B A, B
A O, A O, A O, A, B, AB A, B, AB
B O, B O, A, B, AB O, B A, B, AB
AB A, B A, B, AB A, B, AB A, B, AB

Rhesus system (CDE)

Another characteristic of blood is Rhesus factor or Rh factor. It is named after the Rhesus monkey, in which the factor was first identified by Karl Landsteiner and Alexander S. Wiener. Individuals either have, or do not have, the Rh factor on the surface of their red blood cells. This is indicated as + or -, and the two groups are described as Rh positive (Rh+) or Rh negative (Rh-), respectively. This is often combined with the ABO type. Type O+ blood is most common, though in some areas type A prevails, and there are other areas in which as many as 80% of the people are type B.

Matching the Rhesus factor is very important, as mismatching (an Rh positive donor to an Rh negative recipient) may cause the production in the recipient of an antibody to the Rh(D) antigen, which could lead to subsequent hemolysis. This is of particular importance in females of or below childbearing age, where any subsequent pregnancy may be affected by the antibody produced. For one-off transfusions, particularly in older males, the use of Rh(D) positive blood in an Rh(D) negative individual (who has no atypical red cell antibodies) may be indicated if it is necessary to conserve Rh(D) negative stocks for more appropriate use. The converse is not true: Rh+ patients do not react to Rh- blood.

Rh disease occurs when an Rh negative mother who has already had an Rh positive child (or an accidental Rh+ blood transfusion) carries another Rh positive child. After the first pregnancy, the mother develops IgG antibodies against Rh+ red blood cells, which can cross the placenta and hemolyse the red cells of the second child. This reaction does not always occur, and is less likely to occur if the child carries either the A or B antigen and the mother does not. In the past, Rh incompatibility could result in stillbirth, or in death of the mother, or both. Rh incompatibility was until recently the most common cause of long term disability in the United States. At first, this was treated by transfusing the blood of infants who survived. At present, it can be treated with certain anti-Rh(+) antisera, the most common of which is Rhogam (anti-D). It can be anticipated by determining the blood type of every child of a RhD- mother; if it is Rh+, the mother is treated with anti-D to prevent development of antibodies against Rh+ red blood cells.

ABO blood type incompatibilities between the mother and child do not cause a similar problem because antibodies to the ABO blood groups are of the IgM type, which do not cross the placenta.

Rh factor frequency

Predicted frequency of Rh factor blood types in populations, based on occurrence of genotype:

population Rh(D)- Rh(D)+
European descent 16% 84%
African descent 0.9% 99.1%
Non-European, non-African 0.1% 99.9%

For Rh- people, there is a risk associated with travelling to parts of the world where supplies of Rh- blood are rare, particularly east Asia. Correspondingly, blood services in these areas may look to encourage westerners to donate blood.

Inheritance

Rh (or the D antigen) is inherited on one locus (on the short arm of the first chromosome, 1p36.2-p34) with two alleles, of which Rh+ is dominant and Rh- recessive. The gene codes for a polypeptide on the red cell membrane. Rh- individuals (dd genotype) do not produce this antigen, and may be sensitized to Rh+ blood.

Two very similar epitopes, Cc and Ee, appear to be closely related to Rh.

Frequency of Rh- alleles by population:

Population Frequency of Rh- allele
European 40-45%
African 3%
Non-African, non-European 1%

Frequency of ABO and Rhesus

Blood types are not evenly distributed throughout the human population. O+ is the most common, AB- is the rarest. There are also variations in blood-type distribution within human subpopulations. The figures given here are for people of European descent.

Type Frequency
O+ 38%
A+ 34%
B+ 9%
O- 7%
A- 6%
AB+ 3%
B- 2%
AB- 1%

One study[1] showed the following distribution of bloodtypes among selected populations:

  1. Native Southamericans: 100% had bloodtype O
  2. Vietnamese: 45% O, 21,4% A, 29,1% B, 4,5% AB
  3. Australian aboriginals: 44,4% O, 55,6% A
  4. Germans: 42,8% O, 41,9% A, 11% B, 4,2% AB
  5. Bengals: 22% O, 24 % A, 38,2% B, 15,7% AB
  6. Saami: 18,2% O, 54,6% A, 4,8% B, 12,4% AB.

Other blood types

There are 27 other blood type systems that exist to describe the presence or absence of other antigens. Many are named after the patients in whom they were initially encountered. They exist alongside the ABO antigens, and hence one can be A Rh-positive, but also have Kell or Lewis positivity or negativity.

  • Diego positive blood is found only among East Asians and Native Americans.
  • MNS systems gives blood types of M, N, and MN. It is useful in tests of maternity or paternity.
  • Duffy negative blood gives partial immunity to malaria, and is found within African populations.
  • The Lutheran system describes a set of 21 antigens.
  • Other systems include Colton, Kell, Kidd, Lewis, Landsteiner-Wiener, P, Yt or Cartwright, XG, Scianna, Dombrock, Chido/Rodgers, Kx, Gerbich, Cromer, Knops, Indian, Ok, Raph, and JMH.

Duffy-type blood presents special problems for blood donation groups and recipients because it occurs in a relatively small segment of the African-descended population, but can cause problems if the recipient isn't properly matched with Duffy-type blood. See Social significance below for more information.

These blood types systems are generally not significant for blood donations, but do have applications in forensic science. A blood type mis-match is powerful evidence for the defence. The blood type systems are more or less independent. This allows for a detailed classification of blood. The most common blood type, when all the systems are taken into account, is found in only 1 in 40 people. Correspondingly, a match across multiple systems can be useful evidence for the prosecution.

Bombay phenotype

Individuals with the rare Bombay phenotype (hh) do not express substance H on their red blood cells, and therefore do not bind A or B antigens. Instead, they produce antibodies to H substance (which is present on all red cells except those of hh genotype) as well as to both A and B antigens, and are therefore compatible only with other hh donors.

Individuals with Bombay phenotype blood groups can only be transfused with blood from other Bombay phenotype individuals. Given that this condition is very rare to begin with, any person with this blood group who needs an urgent blood transfusion may be simply out of luck, as it would be quite unlikely that any blood bank would have any in stock. Those anticipating the need for blood transfusion (e.g. in scheduled surgery) may bank blood for their own use (i.e. an autologous blood donation) but this option is not available in cases of accidental injury.

Patients who test as type O may have the Bombay phenotype if they have inherited two recessive alleles of the H gene, (their blood group is Oh and their genotype is "hh"), and so do not produce the "H" carbohydrate that is the precursor to the "A" and "B" antigens. It then no longer matters whether the A or B enzymes are present or not, as no A or B antigen can be produced since the precursor antigen is not present.

Despite the designation O, Oh negative is not a sub-group of any other group, not even O negative or O positive. When this blood group was first encountered, it was found not to be of either group A or B and so was thought to be of group O. But on further testing, it did not match even for O negative or O positive because of the absence of antigen 'H'. The H antigen is a precursor to the A and B antigens. For instance, the B allele must be present to produce the B enzyme that modifies the H antigen to become the B antigen. It is the same for the A allele. However, if only recessive alleles for the H antigen are inherited (hh), as in the case above, the H antigen will not be produced. Subsequently, the A and B antigens also will not be produced. The result is an O phenotype by default since a lack of A and B antigens is the O type. The blood phenotype was first discovered in Bombay, now known as Mumbai, in India.

McLeod phenotype

McLeod phenotype (or McLeod syndrome) is an X-linked anomaly of the Kell blood group system; as a result, the red cells react poorly with Kell antisera. The McLeod gene encodes a protein that has the structural characteristics of a membrane transport protein with an unknown function. Affected cells lack the product of this gene, called KX or XK, that appears to be required for proper synthesis of the Kell antigens.

McLeod males have variable acanthocytosis, secondary to a defect in the inner leaflet bilayer, as well as mild hemolysis. McLeod females have only occasional acanthocytes and very mild hemolysis; the lesser severity is thought to be due to X chromosome inactivation via the Lyon effect. Some McLeod patients develop a neuropathy or psychiatric symptoms, producing a syndrome that may mimic chorea.

Compatibility

In order to provide maximum benefit from each blood donation and to extend shelf-life, blood banks fractionate whole blood into several products that may have varying degrees of compatibility depending upon the recipient's blood type. The most common of these products are packed red blood cells (RBC's), plasma, platelets, and fresh frozen plasma (FFP), which is quick-frozen to retain labile clotting factors V and VII, and usually administered to patients who have a potentially fatal clotting problem caused by a condition such as as advanced liver disease, overdose of anticoagulant, or disseminated intravascular coagulation (DIC). See cryoprecipitate.

In the United States, human blood products are considered drugs. They are tightly regulated by the Food and Drug Administration (FDA), and their use must be ordered by a licensed physician or surgeon.

Ideally, a patient should receive type-specific blood products to minimize the chance of a transfusion reaction. If time allows, the risk will further be reduced by crossmatching blood, in addition to typing both recipient and donor. Crossmatching involves mixing a sample of the recipient's blood with the donor blood and checking to see if the mixture agglutinates, or forms clumps. Blood bank technicians usually check for agglutination with a microscope, and if it occurs, the donor blood that was checked cannot be transfused. A blood transfusion is a risky medical procedure, and typing and crossmatching is standard except in emergencies. Because cross-matching takes about 45 minutes, but blood typing takes only 3 minutes, cross-matching is sometimes omitted in emergency cases.

Persons with blood type O negative are often called "universal donors," and those with type AB positive blood are called "universal recipients," but this is misleading and only true for transfusions of packed red cells. With respect to transfusions of plasma, this situation is reversed. O negative plasma can only be given to O negative recipients, while patients of all blood types can receive AB positive plasma because it contains no anti-A, anti-B, or anti-D antigens. Platelets have no blood type, and are freely transfused. They are usually lumped together in "ten-packs," which are plastic pouches containing the platelets removed by apheresis from ten pints of blood. They are administered to patients who cannot clot due to thrombocytopenia (low platelet count).

The terms "universal donor" and "universal recipient" aren't very useful, because they only consider the reaction of the patient's antibodies to received blood, and not the antibodies present in that blood. Thus, although a transfusion of O- blood to an A or B-typed person is unlikely to cause an immune reaction from the recipient's antibodies, the transfused blood may itself contain antibodies to the patient's A and B antigens; this can cause an adverse reaction, although the risk is far less than that of an O- person receiving types A or B. For this reason, an exact ABO-type match is preferable where circumstances allow. Additionally, the other red blood cell surface antigens that belong to blood groups outside of the ABO convention might cause an adverse reaction.

This is further complicated by the fact that an Rh negative patient can theoretically receive Rh positive blood once, unless the patient is female and she has been pregnant with an Rh positive fetus. A second exposure to Rh positive blood in an Rh negative patient in one lifetime is usually fatal, because the patient's blood will have developed antibodies to the Rh factor.


RBC compatibility chart
Recipient Blood Type Donor must be
AB+ Any blood type
AB- O- A- B- AB-
A+ O- O+ A- A+
A- O- A-    
B+ O- O+ B- B+
B- O- B-    
O+ O- O+    
O- O-      


Plasma compatibility chart
Recipient Blood Type Donor must be
AB any AB
A any A or AB
B any B or AB
O any O, A, B or AB

Evolutionary significance

Some blood types may offer protection from certain disorders and illnesses. For example, Duffy-type blood offers protection against malaria, and is more common in ethnic groups from areas with a high incidence of malaria, probably as a result of natural selection.

The autosomal recessive disorder sickle-cell anemia (so named because it causes red blood cells to become flatter and sickle-shaped) is found primarily in people of African descent; while this condition causes significant health problems, the same gene also gives resistance to malaria. This resistance is a dominant trait, so somebody who inherits only one copy of the sickle-cell gene enjoys better resistance to malaria without the problems of anemia. This offers carriers an evolutionary advantage in malaria-prone areas, an example of heterozygote advantage.

Social significance

In Nazi Germany much research was done to associate blood type with personal characteristics. Especially, researchers tried to associate B-type blood with inferior characteristics. B-type blood was relatively common among German Jewish populations. This research has since been discredited.

Members of the Nazis' elite S.S. troop were tattooed with their blood type; this enabled prioritisation of treatment by medics and ensured that they could be quickly issued the correct blood.

Certain nationalist or ethnic pride movements such as the Basque consider blood type to be a valid indicator of one's racial or ethnic identity.

Rare blood types can cause supply problems for blood banks and hospitals. For example, U-negative and Duffy-negative are two blood groups that occur only within people of African origin, and even then they are rare traits. The rarity of these factors can result in a shortage of U-negative and Duffy-negative blood for patients of African ethnicity.

The Japan blood type theory of personality is a popular belief that a person's ABO blood type is predictive of their personality, character, and compatibility with others. This belief has carried over to certain extent in other parts of East Asia such as South Korea and Taiwan. In Japan, asking someone their blood type is considered as normal as asking their astrological sign.

See also

References

  1. ^ Mourant el al 1976
  • Landsteiner K. Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe. Zentralblatt Bakteriologie 1900;27:357-62.
  • Landsteiner K, Wiener AS. An agglutinable factor in human blood recognized by immune sera for rhesus blood. Proc Soc Exp Biol Med 1940;43:223-224.
  • [Benes93] Beneš, J. Člověk. Praha: Mladá fronta, 1993.