Blood
Groups and Transfusions
If samples of blood from different individuals are mixed together, some
combinations result in red cells sticking together as clumps (Figure 9a). This
is called agglutination, and occurs when the blood groups are
incompatible. It is caused when antigens (or agglutinogens) on the red
cell membrane react with specific antibodies (or agglutinins) in the
plasma. If the quantity (or titre) of antibodies is sufficiently high,
they bind to their antigens on several red cells and glue the cells together,
which then rupture (haemolyse). If this occurs following a blood
transfusion it can lead to anaemia and other serious complications. The most
important blood groups are the ABO system and Rh (Rhesus)
groups.
The ABO system consists of four blood groups: A, B, AB and
O. The precise group depends on the presence or absence of two antigens,
A and B, on the red cells, and their respective antibodies, α and β, in the
plasma (Figure 9b). The A and B antigens on red cells are mostly glycolipids
that differ in respect of their terminal sugar. The antigens are also found as
glycoproteins in other tissues, including salivary glands, pancreas, lungs and
testes, and in saliva and semen.
Group A blood contains the A antigen and β antibody, and group B the B
antigen and α antibody. Group AB has both A and B antigens, but neither
antibody. Group O blood contains neither antigen, but both α and β antibodies.
Group A blood cannot therefore be transfused into people of group B, or vice
versa, because antibodies in the recipient react with their respective antigens
on the donor red cells and cause agglutination (Figure 9c). As people of group
AB have neither α nor β antibodies in the plasma, they can be transfused with
blood from any group, and are called universal recipients. Group O red
cells have neither antigen, and can therefore be transfused into any patient.
People of group O are therefore called universal donors. Although group
O blood contains both antibodies, this can normally be disregarded as they are
diluted during transfusion and are bound and neutralized by free A or B
antigens in the recipient’s plasma. If large or repeated transfusions are
required, blood of the same group is used.
Inheritance of ABO blood groups
The expression of
A and B antigens is determined genetically. A and B allelomorphs (alternative
gene types) are dominant, and O recessive. Therefore AO (heterozygous)
and AA (homozygous) genotypes both have group A phenotypes. An AB
genotype produces both antigens, and is thus group AB. The proportion of each
blood group varies according to race (Figure 9d), although group O is most
common (35–50%). Native Americans are almost exclusively group O.
In ∼85% of the population the red cells have a D antigen on
the membrane (Figure 9e). Such people are called Rh+ (Rhesus positive), while
those who lack the antigen are Rh– (Rhesus negative). Unlike ABO antigens, the
D antigen is not found in other tissues. The antibody to D antigen (anti-D
agglutinin) is not normally found in the plasma of Rh−individuals, but
sensitization and subsequent antibody production occurs if a relatively small
amount of Rh+ blood is introduced. This can result from transfusion, or when an
Rh− mother has an Rh+ child, and fetal red blood cells enter the maternal
circulation during birth. Occasionally, fetal cells may cross the placenta
earlier in the pregnancy.
Inheritance of Rh groups
The gene corresponding to the D antigen is also called D, and is
dominant. When D is absent from the chromosome, its place is taken by the
allelomorph of D called d, which is recessive. Individuals who are homozygous
and heterozygous for D will be Rh+. About 50% of the population are
heterozygous for D, and ∼35% homozygous. Blood typing for
Rh groups is routinely performed for prospective parents to determine the
likelihood of haemolytic disease in the offspring.
Haemolytic disease of the newborn
Most pregnancies with Rh–mothers and Rh+ fetuses are normal, but in some
cases a severe reaction occurs. Anti-D antibody in the mother’s blood can cross
the placenta and agglutinate fetal red cells expressing D antigen. The titre of
antibody is generally too low to be of consequence during a first pregnancy
with a Rh+ fetus, but it can be dangerously increased during subsequent pregnancies,
or if the mother was previously sensitized with Rh+ blood. Agglutination of the
fetal red cells and consequent haemolysis can result in anaemia and other
complications. This is known as haemolytic
disease of the newborn or erythroblastosis fetalis. The haemoglobin
released is broken down to bilirubin, which in excess results in jaundice (yellow
staining of the tissues). If the degree of agglutination and anaemia is severe,
the fetus develops severe jaundice and is grossly oedematous (hydrops
fetalis), and often dies in utero or shortly after birth.
Prevention and treatment In previously unsensitized
mothers, sensitization can be prevented by treatment with anti-D immunoglobulin
after birth. This destroys any fetal Rh+ red cells in the maternal circulation
before sensitization of the mother can occur. If haemolytic disease is evident
in the fetus or newborn, the Rh+ blood can be replaced by Rh− blood immediately
after birth. By the time the newborn infant has regenerated its own Rh+ red
cells, the anti-D antibody from the mother will have been reduced to safe
levels. Phototherapy is commonly used for jaundice, as light converts bilirubin
to a more rapidly eliminated compound.
Other blood groups
Although there are other blood groups, these are of little clinical
importance, as humans rarely develop antibodies to the respective antigens.
However, they may be of importance in medicolegal situations, such as
determination of paternity. An example is the MN group, which is a product of
two genes (M and N). A person can therefore be MM, MN or NN, each genome coming
from one parent. As with the other groups, analysis of the respective parties’
genomes can only determine that the man is not the father. This method
has been largely superceded by DNA profiling.
Complications of blood transfusions
Blood type incompatibility When the recipient of a blood
trans- fusion has a significant plasma titre of α, β or anti-D antibodies,
donor red cells expressing the respective antigen will rapidly agglutinate and
haemolyse (haemolytic transfusion reaction). If the sub- sequent
accumulation of bilirubin is sufficiently large, haemolytic jaundice develops.
In severe cases renal failure may develop. Anti- bodies in the donor blood are
rarely problematical, as they are diluted and removed in the recipient.
Transmission of infection as a result of bacteria, viruses
and para- sites. Most important are hepatitis, HIV, prions and in endemic areas
parasites such as malaria.
Iron overload resulting from frequent transfusions and
break- down of red cells (transfusion haemosiderosis), for example in thalassaemia
(see Chapter 6). Can cause damage to heart, liver, pancreas and glands.
Treatment: iron chelators and vitamin C.
Fever resulting from an immune response to transfused
leucocytes which release pyrogens. Relatively common but mild in patients who
have previously been transfused, and in pregnancy.
Electrolyte changes and suppression of haemostasis following
massive transfusions (e.g. major surgery) with stored blood (see below).
Blood storage
Blood is stored for transfusions at 4°C in the presence of an agent that
chelates free Ca2+ to prevent clotting; for example, citrate, oxalate and
ethylenediaminetetraacetic acid (EDTA; see Chapter 7). Even under these
conditions the red cells deteriorate, although they last much longer in the
presence of glucose, which provides a metabolic substrate. The cell membrane
Na+ pump works more slowly in the cold, with the result that Na+ enters the
cell, and K+ leaves. This causes water to move into the cell so that it swells,
and becomes more spherocytic. On prolonged storage the cells become fragile,
and haemolyse (fragment) easily. Neither leucocytes nor platelets
survive storage well, and disappear within a day of transfusion. Blood banks
normally remove all the donor agglutinins (antibodies), although for small
transfusions these would be sufficiently diluted to be of no threat. Great care
is taken to screen potential donors for blood-borne diseases (e.g. hepatitis, HIV).
