BLOOD GROUPS AND TRANSFUSION

We will talk about

1- Differentiation of red cell antigens from antibodies in persons with type A, B, AB and O blood groups

2- Rh blood types

3- The pathogenesis of the hemolytic disease of newborn

The A and B Antigens: The membranes of human red cells contain a variety of antigens called agglutinogens. The most important and best known of these are A and B agglutinogens, and individuals are divided into 4 major blood types O A B 47 % 41 % 9%

AB 3 %

The A and B agglutinogens are glycoproteins that differ in composition by only one sugar residue. Type A individuals have enzyme (glycosyltransferase A) (GTA) that puts acetylgalactosamine on the glycoprotein skeleton, whereas type B individuals have an enzyme (glycosyltransferase B) (GTB) that puts galactose on the skeleton. Type AB blood have both enzymes.

 The ABO blood groups are genetically determined. The type O gene is apparently functionless in production of a red cell antigen. Each of the other antigens is expressed by the presence of a strong antigen on the surface of the red blood cell. Six genotypes, or gene combinations result in four phenotypes, or blood type expressions.

 Two genes, one on each of two paired chromosomes, determine the A-B-O blood groups. These two genes are allelomorphic genes that can be any one of three different types, but only one type on each chromosome.

Six possible combinations of genes (genotypes) are:

Inheritance of ABO blood type

AO A O AO A O

AA

AO
AA A

AO
AO A O

OO

AA

AO

Group A There are about 20 different known subgroups. A1 and A2 individuals make up the vast majority of people with A blood type, all other subgroups equal less than 1% of A's.

A1 and A2 Subgroups

These are the most important subgroups in the system.

A1 equals approximately 80% of the entire A blood type population, and A2 makes up the remaining 20%, under

current data. This means that all other subgroups must be

rare. Differences between A1 and A2 A1 red blood cells have about one million A antigens per cell. A2 red cells have only 250,000 A antigens per cell, or onefourth the amount that A1 cells have.

A1 and A2 Blood Cell and Antigens A1 Red Cell A2 Red Cell

Red blood Cell

Ceramide

Glucose

Galactose

N-Acetyl Glucosamine

Fucose

N-Acetyl Galactosamine

Agglutinins Antibodies

against

agglutinogens

are

called

agglutinins (most of them are IgM and IgG molecules). Immediately after birth the quantity of agglutinins in the plasma is almost zero. Two to 8 months after birth, the infant begins to produce agglutinins. The

maximum titer is usually reached at 8 to 10 years of age.

 Why are these agglutinins produced in the individuals

who do not have the antigenic substrates in their

RBCs? Probably small amounts of group A and B antigens

enter the body in the food, in bacteria and in other

ways and initiate the development of the anti-A or

anti-B agglutinins.

The Agglutination Process in Transfusion Reactions: Dangerous hemolytic transfusion reactions occur when blood is transfused into an individual with an

incompatible blood type, ie. an individual who has agglutinins against the red cells in the transfusion.

 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 recipient's plasma has agglutinins against the donor's red cells, the cells agglutinate and hemolyze

 Hemolysis occur as early hemolysis (activation of complement system) or as a result of phagocytosis of agglutinated cells (late hemolysis). Free hemoglobin is liberated into the plasma. The severity of 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.

Blood Typing:

Blood typing is performed by mixing an individual's red cells with appropriate antisera on a slide and seeing if agglutination occurs.

 Persons with type AB blood are universal recipients Type O individuals are universal donors This does not mean, however, that blood should ever be transfused without being cross matched except in the most extreme emergencies, since the possibility of reactions or sensitization due to incompatibilities other than ABO incompatibilities always exist.

In cross-matching, donor red cells are mixed with recipient plasma on a slide and checked for agglutination.

It is advisable to check the action of the donor's plasma on the recipient cells even though this is rarely a source of trouble.

The Rh Blood Types: Along with the A-B-O system the most important other system in the transfusion of bloods is the Rh system. The Rh blood group system consists of 50 defined blood-group antigens

 There are six common types of Rh antigens each of which is called an Rh factor. These types are designated C, D, E, c, d, and e. A person who has a C antigen will not have the c antigen, but the person missing the C antigen will always have the c antigen. The type D antigen is widely prevalent in the population and it is also considerably more antigenic than other Rh antigens.

Therefore anyone who has this type of antigen is said to be Rh positive, whereas those persons who do not have the type D antigen are said to be Rh negative

Approximately 85 % of all whites are Rh positive, and 15 percent , Rh negative.

The one major difference between the A-B-O system and the Rh system: - In the A-B-O system, the agglutinins responsible for causing transfusion reactions develop spontaneously, whereas in the Rh system spontaneous agglutinins almost never occur. Instead the person must first be massively exposed to an Rh antigen.

 D-negative individuals (Rh-) who have received a transfusion of D-positive blood (even years previously) can have appreciable anti-D titers and thus may develop transfusion reactions when transfused again with D-positive blood.

Hemolytic Disease of Newborn: Another complication due to Rh incompatibility arises when an Rhnegative 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 of anti-Rh agglutinins during the postpartum period.

 During the next pregnancy, the mother's agglutinins cross the placenta to the fetus. In addition, there are some cases of fetal maternal hemorrhage during pregnancy and

sensitization can occur during pregnancy. In any case, when anti-Rh agglutinins cross the placenta to an Rh positive fetus, they can cause hemolysis and various forms of hemolytic disease of newborn (erythroblastosis fetalis).

 About 50% of Rh-negative individuals are sensitized (developed an anti-Rh titer) by transfusion of Rh-positive blood. Since sensitization of Rh-negative mothers by carrying an Rh-positive fetus generally occurs at birth, the first child is usually normal. However, hemolytic disease occurs in about 17% of the Rhpositive fetuses born to Rh-negative mothers who have previously pregnant to Rh-positive fetuses.

 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 (gamma-globulin-containing Rh antibody), Rh D-immune globulin during the post partum period. Such passive immunization does not harm the mother and has been demonstrated to prevent active antibody formation by the mother.

 After sensitization has developed, the immune globulin is of no value. Treatment with a small dose during pregnancy will also prevent sensitization due to fetal maternal hemorrhage before delivery.

 If hemolysis in the fetus is severe, the infant may die in utero or may develop anemia, severe jaundice, and edema (hydrops fetalis). Kernicterus, a neurologic syndrome in which bile pigments are deposited in the basal ganglia, may also develop, especially if birth is complicated by a period of hypoxia. Bile pigments do not enter the brain in the adult, but in the fetus and newborn infant the bloodbrain barrier is not developed.

The Physiologic Jaundice: In the first week of life, about 60% of term and 80% of preterm neonates are jaundiced. This physiologic jaundice appears in term infants on the second or third days of life , and bilirubin levels peak at less than 12 mg/dl.

This complication probably is related to the increased fetal red cell breakdown and inability of the immature liver to conjugate bilirubin.
Exposure of the skin to white light converts bilirubin to lumirubin, which has a shorter half life than bilirubin

 When jaundice appears at atypical times (i.e., at birth or after 1 week) the cause is sought to prevent exaggerated hyperbilirubinemia and its toxic consequences. Many factors cause elevated bilirubin levels in the neonate: Breast feeding (4-7 days after birth, fatty acids in milk inhibit bilirubin conjugation and there is an increased absorption of bilirubin in the duodenum). Hemolytic disease of newborn Hypoxia Infections Acidosis Albumin binding drugs Liver disease Biliary obstruction

There is no substitute for human blood.

After donating blood, you replace these red blood cells within four weeks. It takes eight weeks to restore the iron lost after donating.

Apheresis (ay-fur-ee-sis) is a special kind of blood donation that allows a donor to give specific blood components, such as platelets

Cancer, transplant and trauma patients, and patients undergoing openheart surgery require platelet transfusions to survive.