IMMUNOHEMATOLOGICAL RESEARCH
Immunohematology is one of the specialized branches of medical science. It deals with the concepts and clinical techniques related to modern transfusion therapy. Efforts to save human lives by transfusing blood have been recorded for several centuries. The era of blood transfusion, however, really began when William Harvey described the circulation of blood in 1616.
The Discovery of ABO Blood Group
In the
Inheritance of the ABO Groups
In 1908, Epstein and Ottenberg suggested that the ABO blood groups were inherited characters. In 1924 Bernstein postulated the existence of three allelic genes. According tothe theory of Bernstein the characters A,B and O are inherited by means of three allelic genes, also called A,B and O . He also proposed that an individual inherited two genes, one from each parent, and that these genes determine which ABO antigen would be present on a person’s erythrocytes. The O gene is considered to be silent (amorphic) since it does not appear to control the development of an antigen on the red cell. Every individual has two chromosomes each carrying either A, B or O, one from each parent, thus the possible ABO genotypes are AA, AO, BB, BO, AB and OO. ABO typing divides the population in to the four groups, group A, B, O and, AB, where the phenotype and the genotype are both AB
The ABO Blood Group
A person’s ABO blood group depends on the antigen present on the red cells.
- Individuals who express the A antigen on their red cell i.e. their red cells agglutinate with anti - A belong to group A.
- Individuals who express the B antigen on their red cells i.e. their red cells agglutinate with anti-B belong to group- B.
- Individuals who lack both the A and B antigen on their red cells that is their red cell show no agglutination either with anti- A or anti- B belong to group O.
- Individuals who express both A and B antigens on their red cells that is their red cells show agglutination with both anti- A and anti –B belong to group AB. The distribution of ABO blood groups differ for various population groups.
Whenever an antigen A and, or B is absent on the red cells, the corresponding antibody is found in the serum
- Individuals who possess the A antigen on their red cells possess anti- B in their serum.
- Individuals who possess the B antigen on their red cells possess anti A in their serum.
- Individuals who possess neither A nor B antigen have both anti A and anti- B in their serum.
- Individuals with both A and B antigens have neither anti A nor anti B in their serum.
Agglutination: is the clumping of particles with antigens on their surface, such as erythrocytes by antibody molecules that form bridges between the antigenic determinants. When antigens are situated on the red cell membrane, mixture with their specific antibodies causes clumping or agglutination of the red cells. An agglutination in which the cells are red cells synonymously called hemagglutination. In hemagglutination the antigen is referred to as agglutinogen and the antibody is referred to as agglutinin. The agglutination of red cells takes place in two stages. In the first stage- sensitization, antibodies present in the serum become attached to the corresponding antigen on the red cell surface. A red cell, which has thus coated by antibodies is said to be sensitized. In the second stage, the physical agglutination or clumping of the sensitized red cells takes place, which is caused by an antibody attaching to antigen on more than one red cell producing a net or lattice that holds the cells together. The cells form aggregates, which if large enough, are visible to the naked eye. There are also degreesof agglutination which can not be seen without the aid of a microscope.
The Right Conditions for RBCs to Agglutinate
The correct conditions must exist for an antibody to react with its corresponding red cell antigen to produce sensitization and agglutination of the red cells, or hemolysis. The following factors affect the agglutination of RBCs:
Antibody size: normally, the forces of mutual repulsion keep the red cells approximately 25 nanometer apart. The maximum span of IgG molecules is 14 nanometer that they could only attach the antigens, coating or sensitizing the red cells and agglutination can not be effected in saline media. On the other hand, IgM molecules are bigger and because of their pentameric arrangement can bridge a wider gap and overcome the repulsive forces, causing cells to agglutinate directly in saline.
pH: the optimum PH for routine laboratory testing is 7.0. Reactions are inhibited when the PH is too acid or too alkaline.
Temperature: The optimum temperature for an antigenantibody reaction
differs for different antibodies. Most IgG antibodies
react best at warm temperature(
Ionic strength: lowering the ionic strength of the medium increases the rate of agglutination of antibody with antigen. Low ionic strength saline (LISS) containing 0.2% NaCl in 7% glucose is used for this purpose rather than normal saline.
Antibody type: Antibodies differ in their ability to agglutinate. IgM antibodies, referred to as complete antibodies, are more efficient than IgG or IgA antibodies in exhibiting in vitro agglutination when the antigen - bearing erythrocytes are suspended in physiologic saline.
Number of antigen sites: Many IgG antibodies of the Rh system fail to agglutinate red cells suspended in saline, however IgG antibodies of the ABO system (anti-A & anti-B) agglutinate these red cells, because there are many A&Bantigen sites (100 times more than the number of Rh sites) than the D site on the cell membrane of erythrocytes.
Centrifugation: centrifugation at high speed attempts to over come the problem of distance in sensitized cells by physically forcing the cells together.
Enzyme treatment: treatment with a weak proteolytic enzymes (eg. Trypsin, ficin, bromelin, papain) removes surface sialic acid residue- by which red cells exert surface negative charge, thereby reducing the net negative charge of the cells, thus lowering the zeta potential, and allowing the cells to come together for chemical linking by specific antibodymolecules. However, enzyme treatment has got a disadvantage in that it destroys some blood group antigens.
Colloidal media: certain anti-D sera especially some IgG antibodies of the Rh system would agglutinate Rh positive potential is carefully adjusted by the addition of the colloid.
Ratio of antibody to antigen: There must be an optimum ratio of antibody to antigen sites for agglutination of red cells to occur. In prozone phenomena (antibody excess), a surplus of antigens combining site which are not bound to antigenic determinants exist, producing false- negative reactions. Thesecan be over come by serially diluting the anti body containing serum. It is also important to ensure that the red cell suspension used in agglutination test must not be too week or too strong, as heavy suspension might mask the presence of a weak antibody.
The ABO blood group system is widely credited to have
been discovered by the Austrian scientist Karl Landsteiner, who found three different blood
types in 1900;he was awarded the Nobel Prize in Physiology or Medicine
in 1930 for his work. Due to inadequate communication at the time it was subsequently
found that Czech serologist Jan Janský had independently pioneered the
classification of human blood into four groups,]
but Landsteiner's independent discovery had been
accepted by the scientific world while Janský
remained in relative obscurity. Janský's
classification is however still used in
Landsteiner described A, B, and O; Alfred von Decastello
and Adriano Sturli
discovered the fourth type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern
discovered the heritability of ABO blood groups in 1910–11, with Felix
Bernstein demonstrating the correct blood group inheritance pattern
of multiple alleles
at one locus in 1924. Watkins and Morgan, in
Blood types is the common of normal antigens signs, which are combined on immunologic and genetic bases
A blood type (also called a blood group) is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins or glycolipids, depending on the blood group system, and some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens, that stem from one allele (or very closely linked genes), collectively form a blood group system.
ABO antigens
Diagram showing the carbohydrate chains that determine the ABO blood group
The H antigen is an essential precursor to the ABO blood group antigens. The H locus, which is located on chromosome 19, contains three exons that span more than 5 kb of genomic DNA; it encodes a fucosyltransferase that produces the H antigen on RBCs. The H antigen is a carbohydrate sequence with carbohydrates linked mainly to protein (with a minor fraction attached to ceramide moiety). It consists of a chain of β-D-galactose
, β-D-N-acetylglucosamine, β-D-galactose, and 2-linked, α-L-fucoseSerology
Origin theories
Rhesus factor
History of discoveries
Rh nomenclature
The Rhesus system antigens
· erythroblastosis refers to the making of immature red blood cells
· Symptoms and signs in the Fetus:
o Enlarged liver, spleen, or heart and fluid buildup in the fetus' abdomen seen via ultrasound.
· Symptoms and signs in the Newborn:
o Anemia which creates the newborn's pallor (pale appearance).
o Enlargement of the newborn's liver and spleen.
o The newborn may have severe edema of the entire body.
o Dyspnea or difficulty breathing.
Early attempts
World War II syringe for direct interhuman blood transfusion
The first successes
While the first transfusions had to be made directly from donor to receiver before coagulation, in the 1910s it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for blood banks. The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, who used sodium citrate as an anticoagulant. The first blood transfusion using blood that had been stored and cooled was performed on January 1, 1916. Oswald Hope Robertson, a medical researcher and U.S. Army officer, is generally credited with establishing the first blood bank while serving in France during World War I.
Following Bogdanov's lead, the Soviet
Union set up a national system of blood banks in the 1930s.
News of the Soviet experience traveled to
Great care is taken in cross-matching to ensure that the recipient's immune system will not attack the donor blood. In addition to the familiar human blood types (A, B, AB and O) and Rh factor (positive or negative) classifications, other minor red cell antigens are known to play a role in compatibility. These other types can become increasingly important in people who receive many blood transfusions, as their bodies develop increasing resistance to blood from other people via a process of alloimmunization.
A number of infectious
diseases (such as HIV,
syphilis,
hepatitis
B and hepatitis
C, among others) can be passed from the donor to recipient. This has led
to strict human blood transfusion standards in developed countries. Standards
include screening for potential risk factors and health problems among donors
by determining donor hemoglobin
levels, administering a set of standard oral and written questions to donors,
and laboratory testing of donated units for infection. The lack of such
standards in places like rural
· Human T-lymphotropic virus (HTLV-1 and HTLV-2)
· Treponema pallidum (the causative agent of syphilis)
Processing of blood prior to transfusion
o Chronically transfused patients
o Potential transplant recipients
o Patients with previous febrile nonhemolytic transfusion reactions
o CMV seronegative at-risk patients for whom seronegative components are not available
o Patients with hereditary immune deficiencies
o Patients receiving blood transfusions from relatives in directed-donation programs
Neonatal transfusion
Terminology
Procedure
Blood transfusions can be grouped into two main types depending on their source:
· Homologous transfusions, or transfusions using the stored blood of others.
· Autologous transfusions, or transfusions using one's own stored blood.
Blood is most commonly donated as whole blood by inserting a catheter into a vein and collecting it in a plastic bag (mixed with anticoagulant) via gravity. Collected blood is then separated into components to make the best use of it. Aside from red blood cells, plasma, and platelets, the resulting blood component products also include albumin protein, clotting factor concentrates, cryoprecipitate, fibrinogen concentrate, and immunoglobulins (antibodies). Red cells, plasma and platelets can also be donated individually via a more complex process called apheresis.
Contraindications to being a blood donor
· previous malaria or hepatitis
· a history of intravenous drug abuse
· donors who have received human-derived pituitary hormones
· donors with high-risk sexual behaviour (variably defined)
· donors who have previously been transfused (12-month min. deferral)
Donating
whole blood at a modern, well-run blood collection center is safe. The
biggest risk is probably that of vasovagal syncope, or "passing out". A
large study, involving 194,000 donations during a one-year period at an urban
· Hematoma at needle site — 2 percent
· Sensory changes in the arm used for donation (eg, burning pain, numbness, tingling) — 1 percent
· Vasovagal symptoms — 5 percent
· Nausea and vomiting — 1 percent
There are risks associated with receiving a blood transfusion, and these must be balanced against the benefit which is expected. The most common adverse reaction to a blood transfusion is a so-called febrile non-hemolytic transfusion reaction, which consists of a fever which resolves on its own and causes no lasting problems or side effects.
Transformation from a type to another
Objections to blood transfusion
As of mid-2006, there are no clinically utilized oxygen-carrying blood substitutes for humans; however, there are widely available non-blood volume expanders and other blood-saving techniques. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood.
Red blood cell compatibility
·
· Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals with type A or AB.
· Blood group B individuals have the B antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals with type B or AB.
· Blood group O (or blood group zero in some countries) individuals do not have either A or B antigens on the surface of their RBCs, and their blood serum contains IgM anti-A and anti-B antibodies against the A and B blood group antigens. Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (i.e., A, B, O or AB). If a patient in a hospital situation were to need a blood transfusion in an emergency, and if the time taken to process the recipient's blood would cause a detrimental delay, O Negative blood can be issued. They are known as universal donors.
·
Red blood cell compatibility chart
In addition to donating to the same blood group; type O blood donors can give to A, B and AB; blood donors of types A and B can give to AB.
Red blood cell compatibility table |
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Recipient |
Donor |
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O− |
O+ |
A− |
A+ |
B− |
B+ |
AB− |
AB+ |
|
O− |
|
|
|
|
|
|
|
|
O+ |
|
|
|
|
|
|
|
|
A− |
|
|
|
|
|
|
|
|
A+ |
|
|
|
|
|
|
|
|
B− |
|
|
|
|
|
|
|
|
B+ |
|
|
|
|
|
|
|
|
AB− |
|
|
|
|
|
|
|
|
AB+ |
|
|
|
|
|
|
|
|
Table note
1. Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching.
An Rh D-negative patient who does not have any anti-D antibodies (never being previously sensitized to D-positive RBCs) can receive a transfusion of D-positive blood once, but this would cause sensitization to the D antigen, and a female patient would become at risk for hemolytic disease of the newborn. If a D-negative patient has developed anti-D antibodies, a subsequent exposure to D-positive blood would lead to a potentially dangerous transfusion reaction. Rh D-positive blood should never be given to D-negative women of child bearing age or to patients with D antibodies, so blood banks must conserve Rh-negative blood for these patients. In extreme circumstances, such as for a major bleed when stocks of D-negative blood units are very low at the blood bank, D-positive blood might be given to D-negative females above child-bearing age or to Rh-negative males, providing that they did not have anti-D antibodies, to conserve D-negative blood stock in the blood bank. The converse is not true; Rh D-positive patients do not react to D negative blood.
This same matching is done for other antigens of the Rh system as C, c, E and e and for other blood group systems with a known risk for immunization such as the Kell system in particular for females of child-bearing age or patients with known need for many transfusions.
Plasma compatibility
Plasma compatibility chart
In addition to donating to the same blood group; plasma from type AB can be given to A, B and O; plasma from types A, B and AB can be given to O.
Recipients can receive plasma of the same blood group, but otherwise the donor-recipient compatibility for blood plasma is the converse of that of RBCs:[citation needed] plasma extracted from type AB blood can be transfused to individuals of any blood group; individuals of blood group O can receive plasma from any blood group; and type O plasma can be used only by type O recipients.
Plasma compatibility table |
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Recipient |
Donor[1] |
|||
O |
A |
B |
AB |
|
O |
|
|
|
|
A |
|
|
|
|
B |
|
|
|
|
AB |
|
|
|
|
Table note
1. Assumes absence of strong atypical antibodies in donor plasma
Rh D antibodies are uncommon, so generally neither D negative nor D positive blood contain anti-D antibodies. If a potential donor is found to have anti-D antibodies or any strong atypical blood group antibody by antibody screening in the blood bank, they would not be accepted as a donor (or in some blood banks the blood would be drawn but the product would need to be appropriately labeled); therefore, donor blood plasma issued by a blood bank can be selected to be free of D antibodies and free of other atypical antibodies, and such donor plasma issued from a blood bank would be suitable for a recipient who may be D positive or D negative, as long as blood plasma and the recipient are ABO compatible.[citation needed]
Universal donors and universal recipients
A hospital corpsman with the Blood Donor Team from Naval Medical Center Portsmouth takes samples of blood from a donor for testing
With regard to
transfusions of packed red blood cells, individuals with type O Rh D negative blood are often called universal donors, and
those with type AB Rh D positive blood are called
universal recipients; however, these terms are only generally true with respect
to possible reactions of the recipient's anti-A and anti-B antibodies to
transfused red blood cells, and also possible sensitization to Rh D antigens. One exception is individuals with hh antigen system (also known as the
Blood donors with particularly strong anti-A, anti-B or any atypical blood group antibody are excluded from blood donation. The possible reactions of anti-A and anti-B antibodies present in the transfused blood to the recipient's RBCs need not be considered, because a relatively small volume of plasma containing antibodies is transfused.
By way of example: considering the transfusion of O Rh D negative blood (universal donor blood) into a recipient of blood group A Rh D positive, an immune reaction between the recipient's anti-B antibodies and the transfused RBCs is not anticipated. However, the relatively small amount of plasma in the transfused blood contains anti-A antibodies, which could react with the A antigens on the surface of the recipients RBCs, but a significant reaction is unlikely because of the dilution factors. Rh D sensitization is not anticipated.
Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response. Transfusions are further complicated because platelets and white blood cells (WBCs) have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion.
With regard to transfusions of plasma, this situation is reversed. Type O plasma, containing both anti-A and anti-B antibodies, can only be given to O recipients. The antibodies will attack the antigens on any other blood type. Conversely, AB plasma can be given to patients of any ABO blood group due to not containing any anti-A or anti-B antibodies.
Blood group genotyping
In addition to the current practice of serologic testing of blood types, the progress in molecular diagnostics allows the increasing use of blood group genotyping. In contrast to serologic tests reporting a direct blood type phenotype, genotyping allows the prediction of a phenotype based on the knowledge of the molecular basis of the currently known antigens. This allows a more detailed determination of the blood type and therefore a better match for transfusion, which can be crucial in particular for patients with needs for many transfusions to prevent allo-immunization
c) Antigens set of rhesus (DCE) system (Aside from the antigens of the ABO system, those of the Rh system are of the greatest clinical importance. The "Rh factor," named for the rhesus monkey because it was first studied in the blood of this animal, is a system composed of many antigens. D is by far the most antigenic, and the term "Rh-positive" as it is generally used means that the individual has agglutinogen D. The "Rh-negative" individual has no D antigen and forms the anti-D agglutinin when injected with D-positive cells. The Rh typing serum used in routine blood typing is anti-D serum. Eighty-five percent of Caucasians are D-positive and 15 % are D-negative; over 99 % of Orientals are D-positive. D-negative individuals who have received a transfusion of D-positive blood (even years previously) can have appreciable anti-D liters and thus may develop transfusion reactions when transfused again with D-positive blood.)
d) Mechanism of development Rh-factor‘s conflict in pregnancy (Another complication due to "Rh incompatibility" arises when an Rh-negative mother carries an Rh-positive fetus. Small amounts of fetal blood leak into the maternal circulation at the time of delivery, and some mothers develop significant titers ofanti-Rh agglutinins during the postpartum period. During the next pregnancy, the mother‘s agglutinins cross the placenta to the fetus. In addition, there are some cases of fetal-maternal hemorrhage during pregnancy, and sensitization can occur during pregnancy. In any case, when anti-Rh agglutinins cross the placenta to an Rh-positive fetus, they can cause hemolysis and various forms of hemolytic disease of the newborn (erythroblastosis fetalis). If hemolysis in the fetus is severe, the infant may die in utero or may develop anemia, severe jaundice, and edema (hydrops fetalis). However, hemolytic disease occurs in about 17% of the Rh-positive fetuses born to Rh-negative mothers who have previously been pregnant one or more times with Rh-positive fetuses. Fortunately, it is possible to prevent sensitization from occurring the first time by administering a single dose of anti-Rh antibodies in the form of Rh immune globulin during the postpartum period. Such passive immunization does not harm the mother and has been demonstrated to prevent active antibody formation by the mother. In obstetric clinics, the institution of such treatmenlon a routine basis to unsensitized Rh-negative women who have delivered an Rh-positive baby has reduced the overall incidence of hemolytic disease by more than 90%. Treatment with a small dose during pregnancy will also prevent sensilization due to fetal-maternal hemorrhage before delivery.)
e) Inheritance of A & B Antigens (The A1, A2, and B antigens are inherited as mendelian allelomorphs, A1, A2, and B being dominants. For example, an individual with type B blood may have inherited a B antigen from each parent or a B antigen from one parent and an 0 from the other; thus, an individual whose phenotype is B may have the genotype BB (homozygous) or the genotype BO (heterozygous).When the blood types of the parents are known, the possible genotypes of their children can be stated. When both parents are type B, they could have children with genotype BB (B antigen from both parents), BO (B antigen from one parent, 0 from the other. heterozygous parent), or 00 (0 antigen from both parents, both being heterozygous). When the blood types of a mother and her child are known, it is possible to state whether a man of a given blood type could or could not have been the father. This has medicolegal importance in paternity cases. It should be emphasized that typing can only prove that a man is not the father, not that he is the father. The predictive value of such determinations is increased if the blood typing of the parties concerned includes identification of antigens other than the ABO agglutinogens. With the addition of HLA typing, the exclusion rate rises to about 92 %.)
Leukocytes and serum blood types
a) Common antigens of leukocytes (These antigens are characteristic for white cells. These is LyD1.)
b) Serum blood types (There are more than 20 immunoglobulin blood cells, albumin and globulin blood types.)
3. Transfusion of blood (We must transfused only blood of one groop with recipient! Before the transfusion we must do the test on individual blood compatibility in AB0 and DCE systems.)
a) Physiological effects of blood, which was transfused (deputy, hemodynamic, hemopoietic, immunologic, degestive.)
b) Transfusion Reactions (Dangerous hemolytic transfusion reactions occur when blood is transfused into an individual with an incompatible blood type. The plasma in the transfusion is usually so diluted in the recipient that it rarely causes agglutination even when the titer of agglutinins against the recipient‘s cells is high. However, when the recipient‘s plasma has agglutinins against the donor‘s red cells, the cells agglutinate and hemolyze. Free hemoglobin is liberated into the plasma. The severity of the resulting transfusion reaction may vary from an asymptomatic minor rise in the plasma bilirubin level to severe jaundice and renal tubular damage (caused in some way by the products liberated from hemolyzed cells), with anuria and death.)
ABO blood group system
The ABO system is the most important blood group system in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies. ABO IgM antibodies are produced in the first years of life by sensitization to environmental substances such as food, bacteria and viruses. The "O" in ABO is often called "0" (zero/null) in other languages.]
The Rhesus system is the second most significant blood group system in human blood transfusion. The most significant Rhesus antigen is the RhD antigen because it is the most immunogenic of the five main rhesus antigens. It is common for RhD negative individuals not to have any anti-RhD IgG or IgM antibodies, because anti-RhD antibodies are not usually produced by sensitization against environmental substances. However, RhD negative individuals can produce IgG anti-RhD antibodies following a sensitizing event: possibly a fetomaternal transfusion of blood from a fetus in pregnany or occasionally a blood transfusion with RhD positive RBCs.
Table of ABO and Rh distribution by nation
ABO and Rh blood type distribution by nation (averages for each population) |
||||||||
Population |
O+ |
A+ |
B+ |
AB+ |
O− |
A− |
B− |
AB− |
Australia |
40% |
31% |
8% |
2% |
9% |
7% |
2% |
1% |
39% |
36% |
7.6% |
2.5% |
7% |
6% |
1.4% |
0.5% |
|
35% |
37% |
8% |
4% |
6% |
7% |
2% |
1% |
|
27% |
38% |
15% |
7% |
4% |
6% |
2% |
1% |
|
36% |
37% |
9% |
3% |
6% |
7% |
1% |
1% |
|
40% |
26% |
27% |
7% |
<0.3% |
<0.3% |
<0.3% |
<0.3% |
|
Korea, South |
27.4% |
34.4% |
26.8% |
11.2% |
0.1% |
0.1% |
0.1% |
0.05% |
31% |
32% |
15% |
7% |
6% |
6% |
2% |
1% |
|
Sweden |
32% |
37% |
10% |
5% |
6% |
7% |
2% |
1% |
UK |
37% |
35% |
8% |
3% |
7% |
7% |
2% |
1% |
USA |
38% |
34% |
9% |
3% |
7% |
6% |
2% |
1% |
Overall,
type O blood is the most common blood type in these parts of the world. Type A
blood is more prevalent in Central and
The International Society of Blood Transfusion currently recognizes 29 blood group systems (including the ABO and Rh systems). Thus, in addition to the ABO antigens and Rhesus antigens, many other antigens are expressed on the RBC surface membrane. For example, an individual can be AB RhD positive, and at the same time M and N positive (MNS system), K positive (Kell system), Lea or Leb negative (Lewis system), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered.
Transfusion medicine is a specialized
branch of hematology
that is concerned with the study of blood groups, along with the work of a blood bank
to provide a transfusion service for blood and other blood
products. Across the world, blood products must be prescribed by a medical
doctor (licensed physician or surgeon) in a similar way as medicines. In the
Much of the routine work of a blood bank involves testing blood from both donors and recipients to ensure that every individual recipient is given blood that is compatible and is as safe as possible. If a unit of incompatible blood is transfused between a donor and recipient, a severe acute immunological reaction, hemolysis (RBC destruction), renal failure and shock are likely to occur, and death is a possibility. Antibodies can be highly active and can attack RBCs and bind components of the complement system to cause massive hemolysis of the transfused blood.
• A person with blood type A can receive blood from a donor with blood type A.
– The anti-B antibodies in the recipient do not combine with the type A antigens on the red blood cells of the donor.
• A person with blood type B cannot receive blood from a donor with blood type A.
– The anti-A antibodies in the recipient will combine with the type B antigens on the red blood cells of the donor.
Patients should ideally receive their own blood or type-specific blood products to minimize the chance of a transfusion reaction. Risks can be further reduced by cross-matching blood, but this may be skipped when blood is required for an emergency. Cross-matching involves mixing a sample of the recipient's blood with a sample of the donor's blood and checking to see if the mixture agglutinates, or forms clumps. If agglutination is not obvious by direct vision, blood bank technicians usually check for agglutination with a microscope. If agglutination occurs, that particular donor's blood cannot be transfused to that particular recipient. In a blood bank it is vital that all blood specimens are correctly identified, so labeling has been standardized using a barcode system known as ISBT 128.
The blood group may be included on identification tags or on tattoos worn by military personel, in case they should need an emergency blood transfusion. Frontline German Waffen-SS had such tattoos during the World War II and ironically this was an easy form of SS identification.
Rare blood types can cause supply problems for blood banks and hospitals. For example Duffy-negative blood occurs much more frequently in people of African origin, and the rarity of this blood type in the rest of the population can result in a shortage of Duffy-negative blood for patients of African ethnicity. Similarly for RhD negative people, there is a risk associated with travelling to parts of the world where supplies of RhD negative blood are rare, particularly East Asia, where blood services may endeavor to encourage Westerners to donate blood.
A pregnant woman can make IgG blood group antibodies if her fetus has a blood group antigen that she does not have. This can happen if some of the fetus' blood cells pass into the mother's blood circulation (e.g. a small fetomaternal hemorrhage at the time of childbirth or obstetric intervention), or sometimes after a therapeutic blood transfusion. This can cause Rh disease or other forms of hemolytic disease of the newborn (HDN) in the current pregnancy and/or subsequent pregnancies. If a pregnant woman is known to have anti-RhD antibodies, the RhD blood type of a fetus can be tested by analysis of fetal DNA in maternal plasma to assess the risk to the fetus of Rh disease. Antibodies associated with some blood groups can cause severe HDN, others can only cause mild HDN and others are not known to cause HDN.
In order to provide maximum benefit from each blood donation and to extend shelf-life, blood banks fractionate some whole blood into several products. The most common of these products are packed RBCs, plasma, platelets, cryoprecipitate, and fresh frozen plasma (FFP). FFP is quick-frozen to retain the labile clotting factors V and VIII, which are usually administered to patients who have a potentially fatal clotting problem caused by a condition such as advanced liver disease, overdose of anticoagulant, or disseminated intravascular coagulation (DIC).
Units of packed red cells are made by removing as as much of the plasma as possible from whole blood units.
Clotting factors synthesized by modern recombinant methods are now in routine clinical use for hemophilia, as the risks of infection transmission that occur with pooled blood products are avoided.
Red blood cell compatibility
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· Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals of groups A or AB.
· Blood group B individuals have the B antigen on their surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals of groups B or AB.
· Blood group O (or blood group zero in some countries) individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains IgM anti-A antibodies and anti-B antibodies against the A and B blood group antigens. Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (ie A, B, O or AB). If a blood transfusion is needed in a dire emergency, and the time taken to process the recipient's blood would cause a detrimental delay, O Neg blood is issued.
Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells.
They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane.
They are named for the rhesus monkey in which they were first discovered.
RBCs that are "Rh positive" express the antigen designated D.
85% of the population is RhD positive, the other 15% of the population is running around with RhD negative blood.
Most anti-A or anti-B antibodies are of the IgM class (large molecules) and these do not cross the placenta.
In fact, an Rh−/type O mother carrying an Rh+/type A, B, or AB foetus is resistant to sensitisation to the Rh antigen.
Her anti-A and anti-B antibodies destroy any foetal cells that enter her blood before they can elicit anti-Rh antibodies in her.
RBC Compatibility chart
Red blood cell compatibility table |
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Recipient blood type |
Donor red blood cells must be: |
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AB+ |
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AB- |
AB+ |
AB- |
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AB- |
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A+ |
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A+ |
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A- |
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A- |
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B+ |
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B+ |
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B- |
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B- |
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O+ |
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O+ |
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O- |
O- |
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A RhD negative patient who does not have any anti-RhD antibodies (never being previously sensitized to RhD positive RBCs) can receive a transfusion of RhD positive blood once, but this would cause sensitization to the RhD antigen, and a female patient would become at risk for hemolytic disease of the newborn. If a RhD negative patient has developed anti-RhD antibodies, a subsequent exposure to RhD positive blood would lead to a potentially dangerous transfusion reaction. RhD positive blood should never given to RhD negative women of childbearing age or to patients with RhD antibodies, so blood banks must conserve Rhesus negative blood for these patients. In extreme circumstances, such as for a major bleed when stocks of RhD negative blood units are very low at the blood bank, RhD positive blood might given to RhD negative females above child-bearing age or to Rh negative males, providing that they did not have anti-RhD antibodies, to conserve RhD negative blood stock in the blood bank.
The converse is not true; RhD positive patients do not react to RhD negative blood.
Transfusion reactions
Donor blood bag with segmented tubing
For a blood donor and recipient to be ABO-compatible for a transfusion, the recipient cannot be able to produce Anti-A or Anti-B antibodies that correspond to the A or B antigens on the surface of the donor's red blood cells (since the red blood cells are isolated from whole blood before transfusion, it is unimportant whether the donor blood has antibodies in its plasma). If the antibodies of the recipient's blood and the antigens on the donor's red blood cells do correspond, the donor blood is rejected.
In addition to the ABO system, the Rh blood group system can affect transfusion compatibility. An individual is either positive or negative for the Rh factor; this is denoted by a '+' or '-' after their ABO type. Blood that is Rh-negative can be transfused into a person who is Rh-positive, but an Rh-negative individual can create antibodies for Rh-positive RBCs.
Because of this, the
ABO blood group incompatibilities between the mother and child does not usually cause hemolytic disease of the newborn (HDN) because antibodies to the ABO blood groups are usually of the IgM type, which do not cross the placenta; however, in an O-type mother, IgG ABO antibodies are produced and the baby can develop ABO hemolytic disease of the newborn.
Inheritance
A and B are codominant, giving the AB phenotype.
Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO 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).
The IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB are dominant over i, only ii people have type O blood. Individuals with IAIA or IAi have type A blood, and individuals with 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. A type A and a type B couple can also have a type O child if they are both heterozygous (IBi,IAi) The cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A1 or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.[19]
Distribution and evolutionary history
The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations.
In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of placenames and to the successive invasions and migrations including Vikings, Danes, Saxons, Celts, and Normans who contributed the morphemes to the placenames and the genes to the population.
There are six common alleles in white individuals of the ABO gene that produce one's blood type:
A |
B |
O |
A101 (A1) |
B101 (B1) |
O01 (O1) |
Many rare variants of these alleles have been found in human populations around the world.
Genetics
There are two common O alleles, O01 and O02. These are identical to the group A allele (A01) for the first 261 nucleotides, at which point a guanosine base is deleted, resulting in a frame-shift mutation that produces a premature stop codon and failure to produce a functional A or B transferase. This deletion is found in all populations worldwide and presumably arose before humans migrated out of Africa (50,000 to 100,000 years ago). The second most common allele for group O (termed O02) is considered to be an even more ancient than the O01 allele.
Some 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. Another theory states that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09, B101, O02 and O01. The continued presence of the O alleles is hypothesized to be the result of balancing selection. Both theories contradict the previously held theory that type O blood evolved earliest.
ABO and Rh distribution by country
Frequency of O group in indigenous populations around the world
Plasma compatibility
Plasma compatibility chart
Plasma from type AB can be given to A, B & O; plasma from types A & B can be given to O.
Donor-recipient compatibility for blood plasma is the reverse of that of RBCs. Plasma extracted from type AB blood can be transfused to individuals of any blood group, but type O plasma can be used only by type O recipients.
Rhesus D antibodies are uncommon, so generally neither RhD negative nor RhD positive blood contain anti-RhD antibodies. If a potential donor is found to have anti-RhD antibodies or any strong atypical blood group antibody by antibody screening in the blood bank, they would not be accepted as a donor; therefore, all donor blood plasma issued by a blood bank can be expected to be free of RhD antibodies and free of other atypical antibodies. Donor plasma issued from a blood bank would be suitable for a recipient who may be RhD positive or RhD negative, as long as blood plasma and the recipient are ABO compatible.
Plasma compatibility table |
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Recipient blood type |
Donor plasma must be: |
AB |
AB |
A |
A or AB |
B |
B or AB |
O |
O, A, B or AB |
Universal donors and universal recipients
With regard to transfusions of whole blood or packed red blood cells, individuals with type O negative blood are often called universal donors, and those with type AB positive blood are called universal recipients. Although blood donors with particularly strong anti-A, anti-B or any atypical blood group antibody are excluded from blood donation, the terms universal donor and universal recipient are an over-simplification, because they only consider possible reactions of the recipient's anti-A and anti-B antibodies to transfused red blood cells, and also possible sensitisation to RhD antigens. The possible reactions of anti-A and anti-B antibodies present in the transfused blood to the recipients RBCs are not considered, because a relatively small volume of plasma containing antibodies is transfused.
By way of example; considering the transfusion of O RhD negative blood (universal donor blood) into a recipient of blood group A RhD positive, an immune reaction between the recipient's anti-B antibodies and the transfused RBCs is not anticipated. However, the relatively small amount of plasma in the transfused blood contains anti-A antibodies, which could react with the A antigens on the surface of the recipients RBCs, but a significant reaction is unlikely because of the dilution factors. Rhesus D sensitisization is not anticipated.
Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response. Transfusions are further complicated because platelets and white blood cells (WBCs) have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion.
With regard to transfusions of plasma, this situation is reversed. Type O plasma can be given only to O recipients, while AB plasma (which does not contain anti-A or anti-B antibodies) can be given to patients of any ABO blood group.
In April 2007 researchers described the use of newly discovered enzymes to convert blood types A, B, and AB into O, which is the universal donor type.
The Japanese 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, according to books by Masahiko Nomi. This belief has carried over to a 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. It is also common for Japanese-made video games (especially role-playing games) and manga series to include blood type with character descriptions.
The blood type diet is an American system whereby people seek improved health by modifying their food intake and lifestyle according to their ABO blood group and secretor status. This system includes some reference to differences in personality, but not to the extent of the Japanese theory.
Pattern of blood group in ABO blood group
Genotypes are in parentheses. Only A and B have two different genotypes.
The ABO antigen is also expressed on the von Willebrand factor (vWF) glycoprotein, which participates in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding, as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group, and individuals with group O blood normally have significantly lower plasma levels of vWF (and Factor VIII) than do non-O individuals. In addition, vWF is degraded more rapidly due to the higher prevalence of blood group O with the Cys1584 variant of vWF (an amino acid polymorphism in VWF): the gene for ADAMTS13 (vWF-cleaving protease) maps to the ninth chromosome (9q34), the same locus as ABO blood type. Higher levels of vWF are more common amongst people who have had ischaemic stroke (from blood clotting) for the first time. The results of this study found that the occurrence was not affected by ADAMTS13 polymorphism, and the only significant genetic factor was the person's blood group.
Disease association
Compared to O group individuals, non-O group (A, AB, and B) individuals have a 14% reduced risk of squamous cell carcinoma and 4% reduced risk of basal cell carcinoma. Conversely, type O blood is associated with a reduced risk of pancreatic cancer. The B antigen links with increased risk of ovarian cancer.] Gastric cancer has reported to be more common in blood group A and least in group O. According to Glass, Holmgren, et al., those in the O blood group have an increased risk of infection with cholera, and those O-group individuals who are infected have more severe infections. The mechanisms behind this association with cholera are currently unclear in the literature. The title of the referenced article is: "Predisposition for cholera of individuals with O blood group. Possible evolutionary significance."
Subgroups
The A blood type contains about twenty subgroups, of which A1 and A2 are the most common (over 99%). A1 makes up about 80% of all A-type blood, with A2 making up the rest.] These two subgroups are interchangeable as far as transfusion is concerned, but complications can sometimes arise in rare cases when typing the blood.
Individuals with the rare
Nomenclature
in Europe and former USSR
Ukraine marine uniform imprint, showing the wearer's blood type as "B (III) Rh+"
In parts of
Examples of ABO and Rhesus D slide testing method
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Blood group O positive: neither anti-A nor anti-B have agglutinated, but anti-Rh has
Result: Blood group A positive: anti-A and anti-Rh have agglutinated but anti-B has not.
In 1665, an English physiologist, Richard Lower, successfully performed the first animal-to-animal blood transfusion that kept ex-sanguinated dogs alive by transfusion of blood from other dogs. In 1667, Jean Bapiste Denys, transfused blood from the carotid artery of a lamb into the vein of a young man, which at first seemed successful. However, after the third transfusion of lamb’s blood the man suffered a reaction and died. Denys also performed subsequent transfusions using animal blood, but most of them were unsuccessful. Later, it was found that it is impossible to successfully transfuse the blood of one species of animal into another species. Due to the many disastrous consequences resulting from blood transfusion, transfusions were prohibited from 1667 to
1818- when James Blundell of England successfully transfused human blood to women suffering from hemorrhage at childbirth. Such species-specific transfusions (within thesame species of animal) seemed to work about half the time but mostly the result was death.
Blood transfusions continued to produce unpredictable results, until Karl Landsteiner discovered the ABO blood groups in 1900, which introduced the immunological era of blood transfusion. It became clear that the incompatibility of many transfusions was caused by the presence of certain factors on red cells now known as antigens. Two main postulates were also drawn by this cientific approach:
1. Each species of animal or human has certain factor on the red cell that is unique to that species,
2. and 2, even each species has some common and some uncommon factor to each other. This landmark event initiated the era of scientific – based transfusion therapy and was the foundation of immunohematology as a science.
The "Light in the Dark theory" suggests that, when budding viruses acquire host cell membranes from one human patient (in particular, from the lung and mucosal epithelium where they are highly expressed), they also take along ABO blood antigens from those membranes, and may carry them into secondary recipients where these antigens can elicit a host immune response against these non-self foreign blood antigens. These viral-carried human blood antigens may be responsible for priming newborns into producing neutralizing antibodies against foreign blood antigens. Support for this theory has come to light in recent experiments with HIV. HIV can be neutralized in in vitro experiments using antibodies against blood group antigens specifically expressed on the HIV-producing cell lines.
The "Light in the Dark theory" suggests a novel evolutionary hypothesis: there is true communal immunity, which has developed to reduce the inter-transmissibility of viruses within a population. It suggests that individuals in a population supply and make a diversity of unique antigenic moieties so as to keep the population as a whole more resistant to infection. A system set up ideally to work with variable recessive alleles.
However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals.