BLOOD GROUPING SYSTEM

The membranes of human red cells contain a variety of blood group antigens, which are also called
agglutinogens. The most important and best known of these are the A and B antigens, but there are many
more.
Red Blood Cell Antigens and Blood Typing
 There are certain molecules on the surfaces of all cells in the body that can be recognized as
foreign by the immune system of another individual. These molecules are known as antigens.
 As part of the immune response, particular lymphocytes secrete a class of proteins called
antibodies that bond in a specific fashion with antigens.
 The specificity of antibodies for antigens can also be compared to the specificity of enzymes
for their substrates, and of receptor proteins for neurotransmitters and hormones.

ABO System
 The distinguishing antigens on other cells are far more varied than the antigens on red blood cells.
 Red blood cell antigens, however, are of extreme clinical importance because their types must be
matched between donors and recipients for blood transfusions.
 There are several groups of red blood cell antigens, but the major group is known as the ABO
system (LIST THE OTHER BLOOD GROUP SYSYEMS ASIDE FROM ABO SYSTEM).
 In terms of the antigens present on the red blood cell surface, a person may be type A (with only
A antigens), type B (with only B antigens), type AB (with both A and B antigens), or type O
(with neither A nor B antigens).
 Each person’s blood type— A, B, or O—denotes the antigens present on the red blood cell
surface, which are the products of the genes (located on chromosome number 9) that code for
these antigens.
 Each person inherits two genes (one from each parent) that control the production of the ABO
antigens.
 The genes for A or B antigens are dominant to the gene for O. The O gene is recessive, simply
because it doesn’t code for either the A or the B red blood cell antigens.
 The genes for A and B are often shown as I A and I B, and the recessive gene for O is shown as the
lowercase i.
 A person who is type A, therefore, may have inherited the A gene from each parent (may have the
genotype I AI A), or the A gene from one parent and the O gene from the other parent (and thus
have the genotype I Ai).
 Likewise, a person who is type B may have the genotype I BI B or I Bi. It follows that a type O
person inherited the O gene from each parent (has the genotype ii), whereas a type AB person
inherited the A gene from one parent and the B gene from the other (there is no dominant-
recessive relationship between A and B).
 The immune system exhibits tolerance to its own red blood cell antigens.
 People who are type A, for example, do not produce anti-A antibodies. Surprisingly, however,
they do make antibodies against the B antigen and, conversely, people with blood type B
make antibodies against the A antigen.
 People with type A blood GROUP have type A antigens on their red blood cells and
antibodies in their plasma against the type B antigen.
  People with type B blood have type B antigens on their red blood cells and antibodies in their
plasma against the type A antigen.
 Therefore, if red blood cells from one blood type are mixed with antibodies from the plasma
of the other blood type, an agglutination reaction occurs. In this reaction, red blood cells stick
together because of antigen-antibody binding.
 People who are type AB develop tolerance to both of these antigens, and thus do not produce
either anti-A or anti-B antibodies. THEY ARE UNIVERSAL RECIPEINT
 Those who are type O, by contrast, do not develop tolerance to either antigen; therefore, they
have both anti-A and anti-B antibodies in their plasma (UNIVERSAL DONORS)
Transfusion Reactions
 Before transfusions are performed, a major crossmatch is made by mixing serum from the
recipient with blood cells from the donor. If the types do not match—if the donor is type A, for
example, and the recipient is type B—the recipient’s antibodies attach to the donor’s red blood
cells and form bridges that cause the cells to clump together, or agglutinate
 Because of this agglutination reaction, the A and B antigens are sometimes called agglutinogens,
and the antibodies against them are called agglutinins.
 Transfusion errors that result in such agglutination can lead to blockage of small blood vessels
and cause hemolysis (rupture of red blood cells), which may damage the kidneys and other
organs.
 In emergencies, type O blood has been given to people who are type A, B, AB, or O. Because
type O red blood cells lack A and B antigens, the recipient’s antibodies cannot cause
agglutination of the donor red blood cells.
 Type O is, therefore, a universal donor—but only as long as the volume of plasma donated is
small, since plasma from a type O person would agglutinate type A, type B, and type AB red
blood cells.
 Likewise, type AB people are universal recipients because they lack anti-A and anti-B antibodies,
and thus cannot agglutinate donor red blood cells.
 (Donor plasma could agglutinate recipient red blood cells if the transfusion volume were too
large.)
 Because of the dangers involved, use of the universal donor and recipient concept is strongly
discouraged in practice.

Rh blood group system, system for classifying blood groups according to the
presence or absence of the Rh antigen, often called the Rh factor, on
the cell membranes of the red blood cells (erythrocytes).
The Rh blood group system was discovered in 1940 by Karl Landsteiner and A.S. Weiner. Since
that time a number of distinct Rh antigens have been identified, but the first and most common
one, called RhD, causes the most severe immune reaction and is the primary determinant of the
Rh trait.

The Rh antigen poses a danger for the Rh-negative person, who lacks the antigen, if Rh-positive
blood is given in transfusion.
Adverse effects may not occur the first time Rh-incompatible blood is given, but the immune
system responds to the foreign Rh antigen by producing anti-Rh antibodies. If Rh-positive blood
is given again after the antibodies form, they will attack the foreign red blood cells, causing them
to clump together, or agglutinate. The resulting hemolysis, or destruction of the red blood cells,
causes serious illness and sometimes death.

A similar hazard exists during pregnancy for the Rh-positive offspring of Rh-incompatible
parents, when the mother is Rh-negative and the father is Rh-positive.

The first child of such parents is usually in no danger unless the mother has acquired anti-Rh
antibodies by virtue of incompatible blood transfusion. During labour, however, a small amount
of the fetus’s blood may enter the mother’s bloodstream. The mother will then produce anti-Rh
antibodies, which will attack any Rh-incompatible fetus in subsequent pregnancies.

This process produces erythroblastosis fetalis, or hemolytic disease of the newborn, which can
be fatal to the fetus or to the infant shortly after birth.

Treatment of erythroblastosis fetalis usually entails one or more exchange transfusions. The
disease can be avoided by vaccinating the mother with Rh immunoglobulin after delivery of her
firstborn if there is Rh-incompatibility. The Rh vaccine destroys any fetal blood cells before the
mother’s immune system can develop antibodies.

HEMOLYTIC DISEASE OF THE NEWBORN (HDN)

What is it?
How does it happen?
Why does it happen?
How can it be prevented?
WHAT IS IT?
Hemolytic disease of the newborn (HDN) used to be a major cause of fetal loss and death among
newborn babies.
The first description of HDN is thought to be in 1609 by a French midwife who delivered twins
—one baby was swollen and died soon after birth, the other baby developed jaundice and died
several days later. For the next 300 years, many similar cases were described in which newborns
failed to survive.
It was not until the 1950s that the underlying cause of HDN was clarified; namely, the newborn's
red blood cells (RBCs) are being attacked by antibodies from the mother. The attack begins
while the baby is still in the womb and is caused by an incompatibility between the mother's and
baby's blood.
HOW DOES IT HAPPEN?
During pregnancy, some of the mother's antibodies are transported across the placenta and enter
the fetal circulation. This is necessary because by the time of birth, newborns have only a
primitive immune system, and the continuing presence of maternal antibodies helps ensure that
they survive while their immune system matures. A downside to this protection is that by
targeting fetal RBCs, maternal antibodies can also cause HDN.
WHY DOES IT HAPPEN?
A major cause of HDN is an incompatibility of the Rh blood group between the mother and
fetus. Most commonly, hemolytic disease is triggered by the D antigen, although other Rh
antigens, such as c, C, E, and e, can also cause problems.
Pregnancies at risk of HND are those in which an Rh D-negative mother becomes pregnant with
an RhD-positive child (the child having inherited the D antigen from the father). The mother's
immune response to the fetal D antigen is to form antibodies against it (anti-D). These antibodies
are usually of the IgG type, the type that is transported across the placenta and hence delivered to
the fetal circulation.
HDN can also be caused by an incompatibility of the ABO blood group. It arises when a mother
with blood type O becomes pregnant with a fetus with a different blood type (type A, B, or AB).
The mother's serum contains naturally occurring anti-A and anti-B, which tend to be of the IgG
class and can therefore cross the placenta and hemolyse fetal RBCs.
HDN due to ABO incompatibility is usually less severe than Rh incompatibility. One reason is
that fetal RBCs express less of the ABO blood group antigens compared with adult levels. In
addition, in contrast to the Rh antigens, the ABO blood group antigens are expressed by a variety
of fetal (and adult) tissues, reducing the chances of anti-A and anti-B binding their target
antigens on the fetal RBCs.
Less common causes of HDN include antibodies directed against antigens of the Kell blood
group (e.g., anti-K and anti-k), Kidd blood group (e.g., anti-Jka and anti-Jkb), Duffy blood group
(e.g., anti-Fya), and MNS and s blood group antibodies. To date, antibodies directed against the
P and Lewis blood groups have not been associated with HDN.
Sensitization to an antigen occurs when the immune system encounters an antigen for the first
time and mounts an immune response. In the case of HDN caused by Rh incompatibility, an Rh
D-negative mother may first encounter the D antigen while being pregnant with an Rh D-positive
child, or by receiving a blood transfusion of Rh D-positive blood. Once a mother has been
sensitized to the D antigen, her serum will contain anti-D. The direct Coombs test (see below)
confirms the presence of anti-D and hence that the mother has been sensitized.
Only a small amount of fetal blood need enter the mother's circulation for sensitization to occur.
Typically, this occurs during the delivery of the first-born Rh D-positive child. Fetal-maternal
hemorrhage is common during labor and is increased during a prolonged or complicated labor,
which in turn increases the risk of sensitization. Sensitization can also occur earlier in the
pregnancy, for example during a prenatal bleed or a miscarriage. It may also occur during
medical procedures, such as a termination of pregnancy or chorionic villus sampling.
The risk of sensitization to the Rh D antigen is decreased if the fetus is ABO incompatible. This
is because any fetal cells that leak into the maternal circulation are rapidly destroyed by potent
maternal anti-A and/or anti-B, reducing the likelihood of maternal exposure to the D antigen.
After maternal sensitization
Initially, the maternal anti-D that is formed at the time of sensitization is of the IgM type,
which cannot cross the placenta. In subsequent pregnancies, a repeat encounter with the Rh D
antigen stimulates the rapid production of type IgG anti-D, which can be transported across the
placenta and enter the fetal circulation. Once in the fetal circulation, anti-D attaches to the Rh D
antigens found on the fetal RBCs, marking them to be destroyed.
The rate of hemolysis determines whether the nature of HDN is mild, moderate, or severe. In
mild cases, the small increase in the rate of hemolysis is tolerated by the fetus. At birth and
during the newborn period, symptoms include a mild anemia and jaundice, both of which may
resolve without treatment.
In cases where there is a greater increase in the rate of hemolysis, the level of bilirubin may still
remain low during the pregnancy because of the ability of the placenta to remove bilirubin from
the fetal circulation. However, after birth the neonate's immature liver is unable to metabolize the
increased amount of bilirubin that instead accumulates in his or her blood. Within 24 hours of
birth, the level of bilirubin may rise dramatically. If levels continue to rise, bilirubin may enter
the brain to cause kernicterus, a potentially fatal condition that leaves permanent neurological
damage in the babies that survive.
An even greater rapid and prolonged destruction of RBCs leads to severe anemia in the fetus.
The liver, spleen, and other organs increase their production of RBCs to compensate for their
loss. The drive to produce RBCs causes the liver and spleen to increase in size
(hepatosplenomegaly), and liver dysfunction can occur.
Immature RBCs (erythroblasts) spill into the circulation, giving rise to the alternative name of
this disease, erythroblastosis fetalis. A complication of severe HDN is hydrops fetalis, in which
the fetal tissues become swollen (edematous). This condition is usually fatal, either in utero or
soon after birth.
HOW CAN IT BE PREVENTED OR MANAGED?
To detect HDN, the presence of maternal anti-Rh IgG must be identified. In vivo, these antibodies
destroy Rh D-positive fetal RBCs, but in vitro, they do not lyse cells or even cause agglutination, making
them difficult to identify. Therefore, the Coombs test is used. This test uses antibodies that bind to anti-
D antibodies.
 Determine Rh status of the mother

 Direct Coombs test: diagnoses HDN

 Indirect Coombs test: used in the prevention of HDN

 If the mother is not sensitized, reduce the risk of future sensitization

 If the mother is sensitized, determine whether the fetus is at risk and monitor accordingly