IMMUNOHEMATOLOGICAL RESEARCH

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 1900, a German Scientist Karl Landsteiner established the existence of the first known blood group system, the ABO system. Classification of the blood group was based on his observation of the agglutination reaction between an antigen on erythrocytes and antibodies present in the serum of individuals directed against these antigens. Where no agglutination had occurred, either the antigen or the antibody was missing from the mixture. Landsteiner recognized the presence of two separate antigens, the A & B antigens. The antibody that reacted with the A antigens was known as anti A, and the antibody that reacted with the B antigen was known as anti B. Based on the antigen present on the red cells, he proposed three separate groups A, B & O. Shortly hereafter, von Decastello and Sturli identified a fourth blood group AB, by demonstrating agglutination of individuals red cells with both anti-A and anti- B.

 

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 persons 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 persons 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(370C) while IgM antibodies, cold reacting antibodies react best at room temperature and coldest temperature(4 to 220C).

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 Russia and states of the former USSR (see below). In America, W.L. Moss published his own (very similar) work in 1910.

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 191011, with Felix Bernstein demonstrating the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Laine's group (1988) found that the band 3 protein expressed a long polylactosamine chain that contains the major portion of the ABH substances attached.[11] Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.

 

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-fucose
, the chain being attached to the protein or ceramide.

The ABO locus, which is located on chromosome 9, contains 7 exons that span more than 18 kb of genomic DNA. Exon 7 is the largest and contains most of the coding sequence. The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to the D-galactose end of the H antigen, producing the A antigen. The B allele encodes a glycosyltransferase that bonds α-D-galactose to the D-galactose end of the H antigen, creating the B antigen.

In the case of the O allele, when compared to the A allele, exon 6 lacks one nucleotide (guanine), which results in a loss of enzymatic activity. This difference, which occurs at position 261, causes a frameshift that results in the premature termination of the translation and, thus, degradation of the mRNA. This results in the H antigen remaining unchanged in case of O groups.

The majority of the ABO antigens are expressed on the ends of long polylactosamine chains attached mainly to band 3 protein, the anion exchange protein of the RBC membrane, and a minority of the epitopes are expressed on neutral glycosphingolipid.

 

Serology

Anti-A and anti-B antibodies (called isohaemagglutinins), which are not present in the newborn, appear in the first years of life. They are isoantibodies, that is, they are produced by an individual against antigens produced by members of the same species (isoantigens). Anti-A and anti-B antibodies are usually IgM type, which are not able to pass through the placenta to the fetal blood circulation. O-type individuals can produce IgG-type ABO antibodies.

 

Origin theories

It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have epitopes similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells (RBCs) that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards influenza virus, whose epitopes are similar enough to the α-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria, such as E. coli, cross-reacting with the α-D-galactose on the B glycoprotein.

 

 

The membranes of human red cells contain a variety of antigens called agglutinogens. The most important and best known of these are the A and B agglutinogens, and individuals are divided into 4 major blood types, types A, B, AB, and 0, on the basis of the agglutinogens present in their red cells. There are A and B antigens in many tissues other than blood. They have been found in salivary glands, saliva, pancreas, kidney, liver, lungs, testes, semen, and amniotic fluid. The A and B agglutinogens are glycoproteins that differ in composition by only one sugar residue. Type A individuals have an enzyme (glycosyltransferase) that puts acetylgalactosamine on the glycoprotein skeleton, whereas type B individuals have an enzyme that puts galactose on the skeleton. Individuals with type AB blood have both enzymes. Antibodies against agglutinogens are called agglutinins. They may occur naturally (ie, be inherited), or they may be produced by exposure to the red cells of another individual. This exposure may occur via a transfusion or during pregnancy, when fetal red cells cross the placenta and enter the circulation of the mother. Agglutinins against A and B agglutinogens are inherited. Thus, individuals with type A blood (ie, those who have agglutinogen A on their red cells) always have an appreciable liter of an antibody against agglutinogen B called the b or anti-B agglutinin. When their plasma is mixed with type B cells, the agglutinins and the B cell agglutinogens react, causing the type B cells to become clumped (agglutinated) and subsequently hemolyzed. Similarly, individuals with type B blood have a circulating titer of an a (anti-A) agglutinin. Individuals with type 0 blood have circulating anti-A and anti-B agglutinins, and those with type AB blood have no circulating agglutinins . Blood typing is performed by mixing an individuals red cells with appropriate antisera on a slide and seeing if agglutination occurs

The ABO blood group system and the Rhesus blood group system are more likely to cause harmful immunological reactions than the other blood group systems. In the routine blood transfusion work of a blood bank, the presence or absence of the three most significant blood group antigens, the A antigen, the B antigen and the RhD antigen (also known as the Rhesus factor or Rhesus D antigen), is determined. This gives the ABO blood group and the RhD antigen status, which are reflected in the common terminology A positive, O negative, etc. with the capital letters (A, B or O) referring to the ABO blood group, and positive or negative referring to the presence or absence of the RhD antigen of the Rhesus blood group system. In the routine preparation and selection of donor blood for blood transfusion, it is not necessary to determine the status of any more blood groups (or antigens), because antibody screening and cross-matching prior to transfusion, detects if there are any other blood group incompatibilities between potential donor blood and intended recipients.

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 %.

If an individual is exposed to a blood group antigen that is not recognised as self, the immune system will produce antibodies that can specifically bind to that particular blood group antigen and an immunological memory against that antigen is formed. The individual will have become sensitized to that blood group antigen. These antibodies can bind to antigens on the surface of transfused red blood cells (or other tissue cells) often leading to destruction of the cells by recruitment of other components of the immune system. It is vital that compatible blood is selected for transfusion and that compatible tissue is selected for organ transplantation. Transfusion reactions involving minor antigens or weak antibodies may lead to minor problems. However, more serious incompatibilities can lead to a more vigorous immune response with massive RBC destruction, low blood pressure, and even death.

Blood types are inherited and represent contributions from both parents. Often, pregnant women carry a fetus with a different blood type from their own, and sometimes the mother forms antibodies against the red blood cells of the fetus, which causes hemolysis of fetal RBCs, and which in turn can lead to low fetal blood counts, a condition known as hemolytic disease of the newborn. Some blood types are associated with inheritance of other diseases; for example, the Kell antigen is associated with McLeod syndrome.[1] Certain blood types may affect susceptibility to infections, an example being the resistance to specific malaria species seen in individuals lacking the Duffy antigen. The Duffy antigen, as a result of natural selection, is less common in ethnic groups from areas with a high incidence of malaria.

The two most significant blood group systems were discovered during early experiments with blood transfusion: the ABO group in 1901 and the Rhesus group in 1937. Development of the Coombs test in 1945, the advent of transfusion medicine, and the understanding of hemolytic disease of the newborn led to discovery of more blood groups. Today, a total of 29 human blood group systems are recognized by the International Society of Blood Transfusion (ISBT). A complete blood type would describe a full set of 29 substances on the surface of RBCs, and an individual's blood type is one of the many possible combinations of blood group antigens. Across the 29 blood groups, over 600 different blood group antigens have been found, but many of these are very rare or are mainly found in certain ethnic groups. Almost always, an individual has the same blood group for life; but very rarely, an individual's blood type changes through addition or suppression of an antigen in infection, malignancy or autoimmune disease. Blood types have been used in forensic science and in paternity testing, but both of these uses are being replaced by DNA analysis, which provides greater certitude.

 

 

The ABO blood group system is the most important blood type system (or blood group system) in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food, bacteria and viruses. ABO blood types are also present in some animals, for example apes such as chimpanzees, bonobos and gorillas.

Rhesus factor

Individuals either have, or do not have, the Rhesus factor (or Rh D antigen) on the surface of their red blood cells. This is usually indicated by 'RhD positive' (does have the RhD antigen) or 'RhD negative' (does not have the antigen) suffix to the ABO blood type. This suffix is often shortened to 'D pos'/'D neg', 'RhD pos'/RhD neg', or +/-. The latter is generally not preferred in research or medical situations, because it can be altered or obscured accidentally.

In simplest terms, there may be prenatal danger to the fetus when a pregnant woman is RhD-negative and the biological father is RhD-positive. But, as discussed below, the situation is considerably more complex than that.

 

 

History of discoveries

The Rhesus system is named after the Rhesus monkey, following experiments by Karl Landsteiner and Alexander S. Wiener, which showed that rabbits, when immunised with rhesus monkey red cells, produce an antibody that also agglutinates the red blood cells of many humans. Landsteiner and Alexander S. Wiener discovered this factor in 1937 (publishing in 1940).[1] The significance of the Rh factor was soon realized. Dr. Phillip Levine working at the Newark Beth Israel Hospital made a connection between the Rh factor and the incidence of erythroblastosis fetalis, and Wiener realized adverse reactions from transfusions were also resulting from the Rh factor. Wiener then pioneered the exchange transfusion to combat erythroblastosis fetalis in newborn infants. This transfusion technique saved the lives of many thousands of infants before intrauterine transfusion was invented which enabled much more severely affected fetuses to be successfully treated. Drs. Neva Abelson and L.K. Diamond co-discovered a simple test for the Rh factor which was widely applied.

 

Rh nomenclature

The Rhesus system has two sets of nomenclatures, one developed by Doctors Fisher and Race and one by Dr. Wiener. Both systems reflected alternate theories of inheritance. The Fisher-Race system, which is more commonly in use today, utilizes the CDE nomenclature. This system originally postulated that there are three closely linked genes on each chromosome. The genes were designated as D and its hypothetical allele d; C and its allele c, E and its allele e. Each gene was supposed to control the product of the corresponding antigen (i.e., D gene produces D antigen, etc.) However, the d gene was hypothetical, not actual.

The Wiener system used the Rh-Hr nomenclature. This system theorized that there was one gene at a single locus on each chromosome of the pair which controls production of multiple antigens. This concept postulated that a gene R gives rise to the blood factors Rho, rh, and hr and the gene r will produce hr and hr.

Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D)). Wieners notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher-Race theory is more widely used.

DNA testing has shown that both theories are partially correct. There are in fact two linked genes, one with multiple specificities and one with a single specificity. Thus, Wiener's postulate that a gene could have multiple specificities (something many did not give credence to originally) has been proven correct. On the other hand, Wiener's theory that there is one gene has proven incorrect, as has the Fischer-Race theory that there are three genes.

The Rhesus system antigens

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.

The proteins which carry the Rhesus antigens are transmembrane proteins, whose structure suggest that they are ion channels. The main antigens are C, D, E, c and e, which are encoded by two gene loci, the D locus and the CE locus. There is no d antigen. Lowercase "d" indicates the absence of the D antigen (the gene is either deleted or nonfunctional).

 

 

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 mothers 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.

Hemolytic disease of the newborn is also called Erythroblastosis Fetalis. This condition occurs when there is an incompatibility between the blood types of the mother and the baby. These terms do not indicate which specific antigen-antibody incompatibility is implicated.

hemolytic comes from two words: hemo (blood) and lysis (destruction) or breaking down of red blood cells

erythroblastosis refers to the making of immature red blood cells

fetalis refers to the fetus

When the condition is caused by the RhD antigen-antibody incompatibility, it is called RhD Hemolytic disease of the newborn (often called Rhesus disease or Rh disease for brevity). Here, sensitization to Rh D antigens (usually by feto-maternal transfusion during pregnancy) may lead to the production of maternal IgG anti-RhD antibodies which can pass through the placenta. This is of particular importance to RhD negative females of or below childbearing age, because any subsequent pregnancy may be affected by the Rhesus D hemolytic disease of the newborn if the baby is Rh D positive. The vast majority of Rh disease is preventable in modern antenatal care by injections of IgG anti-D antibodies (Rho(D) Immune Globulin). The incidence of Rhesus disease is mathematically related to the frequency of RhD negative individuals in a population, so Rhesus disease is rare in East Asians and Africans, but more common in Caucasians.

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                       Jaundice or yellow discoloration of the newborn's skin, sclera or mucous membrane. This may be evident right after birth or after 24 - 48 hours after birth. This is caused by bilirubin (one of the end products of red blood cell destruction).

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.

Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia or thrombocytopenia caused by a blood disease. People suffering from hemophilia or sickle-cell disease may require frequent blood transfusions.

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 recipients cells is high. However, when the recipients plasma has agglutinins against the donors 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 dead.

 

Early attempts

The first historical attempt at blood transfusion was described by the 15th-century chronicler Stefano Infessura. Infessura relates that, in 1492, as Pope Innocent VIII sank into a coma, the blood of three boys was infused into the dying pontiff's veins at the suggestion of a physician. The boys were ten years old, and had been promised a ducat each. All three died. Some authors have discredited Infessura's account, accusing him of anti-papalism.

World War II syringe for direct interhuman blood transfusion

With Harvey's discovery of the circulation of the blood, more sophisticated research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts on humans continued to have fatal results.

The first fully-documented human blood transfusion was administered by Dr. Jean-Baptiste Denys on June 15, 1667. He transfused the blood of a sheep into a 15-year old boy, who recovered. Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to small amount of animal's blood that was actually transfused into these people. This allowed them to withstand the allergic reaction. Then, Denys performed several transfusions into Mr. Mauroy, who on the third account had died (read "Blood and Justice"). Much controversy surrounded his death and his wife was accused of his murder; it's likely that the transfusion caused his death.

Richard Lower examined the effects of changes in blood volume on circulatory function and developed methods for cross-circulatory study in animals, obviating clotting by closed arteriovenous connections. His newly devised instruments eventually led to actual transfusion of blood.

"Many of his colleagues were present towards the end of February 1665 selected one dog of medium size, opened its jugular vein, and drew off blood, until. its strength was nearly gone . Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed it was overfilled by the inflowing blood." After he "sewed up the jugular veins," the animal recovered "with no sign of discomfort or of displeasure."

Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable Boyle to acquaint the Royal Society with the procedure for the whole experiment," which he did in December of 1665 in the Societys Philosophical Transactions. Denys professor in Paris carried out the first transfusion between humans and claimed credit for the technique, but Lowers priority cannot be challenged.

Six months later in London, Lower performed the first human transfusion in England, where he "superintended the introduction in his arm at various times of some ounces of sheeps blood at a meeting of the Royal Society, and without any inconvenience to him. The recipient was Arthur Coga, "the subject of a harmless form of insanity." Sheeps blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that the shy might be made outgoing by blood from more sociable creatures. Lower wanted to treat Coga several times, but his patient wisely refused. No more transfusions were performed. Shortly before, Lower had moved to London, where his growing practice soon led him to abandon research.

The first successes

The science of blood transfusion dates to the first decade of the 19th century, with the discovery of distinct blood types leading to the practice of mixing some blood from the donor and the receiver before the transfusion (an early form of cross-matching).

Dr. James Blundell, a British obstetrician, performed the first successful transfusion of human blood, for the treatment of postpartum hemorrhage. He used the patient's husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Dr. Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented many instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $50 million in real dollars (adjusted for inflation).

St. George's Hospital Medical School in London, Samuel Armstrong Lane, aided by Dr. Blundell, performed the first successful whole blood transfusion to treat hemophilia.

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.

The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in 1925. Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood.

In fact, following the death of Vladimir Lenin, Bogdanov was entrusted with the study of Lenin's brain, with a view toward resuscitating the deceased Bolshevik leader. Tragically, but perhaps not unforeseeably, Bogdanov lost his life in 1928 as a result of one of his experiments, when the blood of a student suffering from malaria and tuberculosis was given to him in a transfusion. Some scholars (e.g. Loren Graham) have speculated that his death may have been a suicide, while others attribute it to blood type incompatibility, which was still incompletely understood at the time.]

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 America, where in 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood bank in the United States. In creating a hospital laboratory that preserved and stored donor blood, Fantus originated the term "blood bank". Within a few years, hospital and community blood banks were established across the United States.

In the late 1930s and early 1940s, Dr. Charles Drew's research led to the discovery that blood could be separated into blood plasma and red blood cells, and that the components could be frozen separately. Blood stored in this way lasted longer and was less likely to become contaminated.

Another important breakthrough came in 1939-40 when Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid citrate dextrose (ACD) solution, which reduces the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer term storage.

Carl Walter and W.P. Murphy, Jr., introduced the plastic bag for blood collection in 1950. Replacing breakable glass bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood. Further extending the shelf life of stored blood was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks.

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 China, where desperate villagers donated plasma for money and had others' red blood cells reinjected, has produced entire villages infected with HIV.

As of mid-2005, all donated blood in the United States is screened for the following infectious agents:

HIV-1 and HIV-2

Human T-lymphotropic virus (HTLV-1 and HTLV-2)

Hepatitis C virus

Hepatitis B virus

West Nile virus

Treponema pallidum (the causative agent of syphilis)

When a person's need for a transfusion can be anticipated, as in the case of scheduled surgery, autologous donation can be used to protect against disease transmission and eliminate the problem of blood type compatibility.

Processing of blood prior to transfusion

Donated blood is sometimes subjected to processing after it is collected, to make it suitable for use in specific patient populations. Examples include:

Leukoreduction, or the removal of stray white blood cells from the blood product by filtration. Leukoreduced blood is less likely to cause alloimmunization (development of antibodies against specific blood types), and less likely to cause febrile transfusion reactions. Also, leukoreduction greatly reduces the chance of cytomegalovirus (CMV) transmission. Leukoreduced blood is appropriate for:

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

Irradiation. In patients who are severely immunosuppressed and at risk for transfusion-associated graft-versus-host disease, transfused red cells may be subjected to irradiation with at least 2500 Gy to prevent the donor T lymphocytes from dividing in the recipient.[4] Irradiated blood products are appropriate for:

o                       Patients with hereditary immune deficiencies

o                       Patients receiving blood transfusions from relatives in directed-donation programs

o                       Patients receiving large doses of chemotherapy, undergoing stem cell transplantation, or with AIDS (controversial).

CMV screening. Cytomegalovirus, or CMV, is a virus which infects white blood cells. Many people are asymptomatic carriers. In patients with significant immune suppression (e.g. recipients of stem cell transplants) who have not previously been exposed to CMV, blood products that are CMV-negative are preferred. Leukoreduced blood products can substitute for CMV-negative products, since the complete removal of white blood cells removes the source of CMV transmission (see leukoreduction above).

Neonatal transfusion

To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precaution to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative for Cytomegalovirus. It is uncertain whether leukodepletion can be adequate for the prevention of CMV, and therefore most guidelines recommend the provision of CMV-negative blood components for newborns or low birthweight infants in whom the immune system is not fully developed.[5] These specific requirements place additional restrictions on blood donors who can donate to babies.

Terminology

The terms type and screen are used for the testing that (1) determines the blood group (ABO compatibility) and (2) checks for alloantibodies. It takes about 45 minutes to complete.

If time allows more extensive testing, a large number of antibodies are screened. This is known as group & screen and can take up to a day.

If there is no time the blood is called "uncross-matched blood". Uncross-matched blood is O-positive or O-negative. O-negative is usually used for children and women of childbearing age.

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 can only be administered intravenously. It therefore requires the insertion of a cannula of suitable caliber. Before the blood is administered, the personal details of the patient are matched with the blood to be transfused, to minimize risk of transfusion reactions. With the recognition that clerical error (eg administering the wrong unit of blood) is a significant source of transfusion reactions, attempts have been made to build redundancy into the matching process that takes place at the bedside.

A unit (up to 500 ml) of blood is typically administered over 4 hours. In patients at risk of congestive heart failure, many doctors administer furosemide to prevent fluid overload. Acetaminophen and/or an antihistamine such as diphenhydramine are sometimes given before the transfusion to prevent a transfusion reaction.

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.

Donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction.

Contraindications to being a blood donor

Blood donation centers in different countries may have different guidelines about who can serve as a blood donor. Common contraindications to being a blood donor include:

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 U.S. blood center, found 178 cases of syncope, for an incidence of 0.09%. Only 5 of these incidents required emergency room attention, and there was one long-term complication. Most syncopal episodes occurred at the refreshment table following donation, leading the authors to recommend that donors spend at least 10 minutes at the refreshment table drinking fluids after donation. A Greek study of over 12,000 blood donors found an incidence of vasovagal events of 0.89%. Another study interviewed 1,000 randomly selected blood donors 3 weeks after donation, and found the following adverse effects: Bruise at the needle site 23 percent

Sore arm 10 percent

Hematoma at needle site 2 percent

Sensory changes in the arm used for donation (eg, burning pain, numbness, tingling) 1 percent

Fatigue 8 percent

Vasovagal symptoms 5 percent

Nausea and vomiting 1 percent

None of these were severe enough to require medical attention in this study. There is no risk of acquiring an infection at a modern, well-run blood donation center.

Donation of blood products via apheresis is a more invasive and complex procedure and can entail additional risks, although this procedure is, overall, still very safe for the donor.

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.

Blood products can rarely be contaminated with bacteria; the risk of severe bacterial infection and sepsis is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.

Transmission of viral infection is a common concern with blood transfusion. As of 2006, the risk of acquiring hepatitis B via blood transfusion in the United States is about 1 in 250,000 units transfused, and the risk of acquiring HIV or hepatitis C in the U.S. via a blood transfusion is estimated at 1 per 2 million units transfused.

Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, non-cardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions.[ Symptoms can range from mild to life-threatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%.[12]

Other risks associated with receiving a blood transfusion include volume overload, iron overload (with multiple red blood cell transfusions), transfusion-associated graft-vs.-host disease, anaphylactic reactions (in people with IgA deficiency), and acute hemolytic reactions (most commonly due to the administration of mismatched blood types).

Transformation from a type to another

Scientists working at the University of Copenhagen reported in the journal Nature Biotechnology in April 2007 of discovering enzymes, which potentially enable blood from groups A, B and AB to be converted into group O. These enzymes do not affect the Rh group of the blood.

Objections to blood transfusion

Objections to blood transfusions may arise for personal, medical, or religious reasons. For example, Jehovah's Witnesses object to blood transfusion primarily on religious grounds, although they have also highlighted possible complications associated with 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.

A number of blood substitutes are currently in the clinical evaluation stage. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results.

 

Erythrocytes blood types

 

a) Determine the idea of blood type Blood types is the common of normal antigens signs, which are combined on immunologic and genetic bases.

b) Antigens and antibodies of AB0 system (The membranes of human red cells contain a variety of antigens called agglutinogens. The most important and best known of these are the A and B agglutinogens, and individuals are divided into 4 major blood types, types A, B, AB, and 0, on the basis of the agglutinogens present in their red cells. There are A and B antigens in many tissues other than blood. They have been found in salivary glands, saliva, pancreas, kidney, liver, lungs, testes, semen, and amniotic fluid. The A and B agglutinogens are glycoproteins that differ in composition by only one sugar residue. Type A individuals have an enzyme (glycosyltransferase) that puts acetylgalactosamine on the glycoprotein skeleton, whereas type B individuals have an enzyme that puts galactose on the skeleton. Individuals with type AB blood have both enzymes. Antibodies against agglutinogens are called agglutinins. They may occur naturally (ie, be inherited), or they may be produced by exposure to the red cells of another individual. This exposure may occur via a transfusion or during pregnancy, when fetal red cells cross the placenta and enter the circulation of the mother. Agglutinins against A and B agglutinogens are inherited. Thus, individuals with type A blood (ie, those who have agglutinogen A on their red cells) always have an appreciable liter of an antibody against agglutinogen B called the b or anti-B agglutinin. When their plasma is mixed with type B cells, the agglutinins and the B cell agglutinogens react, causing the type B cells to become clumped (agglutinated) and subsequently hemolyzed. Similarly, individuals with type B blood have a circulating titer of an a (anti-A) agglutinin. Individuals with type 0 blood have circulating anti-A and anti-B agglutinins, and those with type AB blood have no circulating agglutinins . Blood typing is performed by mixing an individuals red cells with appropriate antisera on a slide and seeing if agglutination occurs.)

 

Red blood cell compatibility

 

 

 

Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood plasma does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but cannot donate blood to any group other than AB. They are known as universal recipients.

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

Recipient

Donor

O−

O+

A−

A+

B−

B+

AB−

AB+

O−

Green tickY

Red XN

Red XN

Red XN

Red XN

Red XN

Red XN

Red XN

O+

Green tickY

Green tickY

Red XN

Red XN

Red XN

Red XN

Red XN

Red XN

A−

Green tickY

Red XN

Green tickY

Red XN

Red XN

Red XN

Red XN

Red XN

A+

Green tickY

Green tickY

Green tickY

Green tickY

Red XN

Red XN

Red XN

Red XN

B−

Green tickY

Red XN

Red XN

Red XN

Green tickY

Red XN

Red XN

Red XN

B+

Green tickY

Green tickY

Red XN

Red XN

Green tickY

Green tickY

Red XN

Red XN

AB−

Green tickY

Red XN

Green tickY

Red XN

Green tickY

Red XN

Green tickY

Red XN

AB+

Green tickY

Green tickY

Green tickY

Green tickY

Green tickY

Green tickY

Green tickY

Green tickY

 

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

Recipient

Donor[1]

O

A

B

AB

O

Green tickY

Green tickY

Green tickY

Green tickY

A

Red XN

Green tickY

Red XN

Green tickY

B

Red XN

Red XN

Green tickY

Green tickY

AB

Red XN

Red XN

Red XN

Green tickY

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 Bombay phenotype) who can only receive blood safely from other hh donors, because they form antibodies against the H antigen present on all red blood cells.

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-factors 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 mothers 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 recipients cells is high. However, when the recipients plasma has agglutinins against the donors 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%

Canada

39%

36%

7.6%

2.5%

7%

6%

1.4%

0.5%

Denmark

35%

37%

8%

4%

6%

7%

2%

1%

Finland

27%

38%

15%

7%

4%

6%

2%

1%

France

36%

37%

9%

3%

6%

7%

1%

1%

Hong Kong, China

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%

Poland

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 Eastern Europe countries. Type B blood is most prevalent in Chinese/Asian communities when compared to other races. Type AB blood is easier to find in Japan, China and Pakistan.

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 USA, blood products are tightly regulated by the Food and Drug Administration.

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.

 

19_14

         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.

19_14

         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

  Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but can donate blood only to another group AB individual.

  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

 

 

 

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Red blood cell compatibility table

Recipient blood type

Donor red blood cells must be:

AB+

 

 

 

 

 

 

AB-

AB+

AB-

 

 

 

 

 

 

AB-

 

A+

 

 

 

A+

 

 

 

 

A-

 

 

A-

 

 

 

 

 

B+

 

 

 

 

 

B+

 

 

B-

 

 

 

 

B-

 

 

 

O+

 

O+

 

 

 

 

 

 

O-

O-

 

 

 

 

 

 

 

 

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 AB+ blood type is referred to as the "universal recipient", as it possesses neither Anti-B or Anti-A antibodies in its plasma, and can receive both Rh-positive and Rh-negative blood. Similarly, the O- blood type is called the "universal donor"; since its red blood cells have no A or B antigens and are Rh-negative, no other blood type will reject it.

 

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 glycosyltransferasethat 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)
A201 (A2)

B101 (B1)

O01 (O1)
O02 (O1v)
O03 (O2)

 

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

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.

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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 Bombay phenotype (hh) do not express antigen H on their red blood cells. As H antigen serves as precursor for producing A and B antigens, the absence of H antigen means the individuals do not have A or B antigens as well (similar to O blood group). However, unlike O group, the H antigen is absent, hence the individuals produce isoantibodies to antigen H as well as to both A and B antigens. In case they receive blood from O blood group, the anti-H antibodies will bind to H antigen on RBC of donor blood and destroy the RBCs by complement-mediated lysis. Therefore Bombay phenotype can receive blood only from other hh donors (although they can donate as though they were type O).

Nomenclature in Europe and former USSR

 

Ukraine marine uniform imprint, showing the wearer's blood type as "B (III) Rh+"

In parts of Europe, the "O" in ABO blood type is substituted with "0" (zero), signifying the lack of A or B antigen. In the former USSR blood types are referenced using numbers and Roman numerals instead of letters. This is Janský's original classification of blood types. It designates the blood types of humans as I, II, III, and IV, which are elsewhere designated, respectively, as O, A, B, and AB. The designation A and B with reference to blood groups was proposed by Ludwik Hirszfeld.

Examples of ABO and Rhesus D slide testing method

 

 

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 lambs 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.