Let's talk about the ABO system, the classic
blood group if you wish, on human red cells.
For some reason, the ABO system attracts lots of interests.
Often people want to know what their blood group is,
even if they are not having a blood transfusion.
It seems to have captured the imagination.
The ABO system results in the inheritance of different
alleles within an important gene.
This gene encodes a protein, which modifies the
protein on red cells.
It is an enzyme that modifies this protein.
There are 3 major types of allele
that you may have inherited: A, B and O. Of course,
remember you've got an allele from your mom and one
from your dad. So you have got two copies of these.
The O allele really does not modify the protein at all
It is a silent gene whereas A and B make slightly
different carbohydrate modification to the protein.
So there's two different structural variants from A and B
and, of course, the original one as well.
The phenotype that results from this is that an individual
can be typed at this protein as O,A ,B or indeed AB
Now, what's important about the ABO system is a
fascinating fact that if you are an A or B,
you make antibodies automatically against
the other type of protein that you lack.
It's a really quite remarkable finding.
Let's go up to that table on the right
and look at these ABO blood groups in more detail.
So the first row says: Antigens on your red cells.
If you are O, you do not have any
these antigens on your red cells.
But if you go to the row below: antibody in serum, an
O individual has antibodies in their blood against A and B.
They are already making those antibodies naturally.
That can be really dangerous if you give a person
who is O, blood from somebody who is A or B
whose antibodies will react immediately.
We will see on the bottom that the O blood group is the most
common in most societies whereas if we go to the person
who's A (the second column), they have A on their red cells
and the antibodies in their serum are against B
and that's also a common phenotype.
B starts to get more unusual, that means you've got B
from your mom and from your dad or O from one of them
and now this person has an anti-A antibody.
That is quite uncommon.
And finally the most rare is AB and that means
you've got A from your mom or B from your dad,
or the other way around, and that is only
3% of the population.
So it's quite a complicated system to understand,
but the key fact is whichever proteins you've got,
you will make antibodies to the other proteins that are
available, and that's important in blood transfusion.
Now let's talk about the rhesus system.
This is also very important in crossmatching,
but the generation of antibodies is slightly different.
The Rhesus system is encoded from two genes.
One of these genes make a protein, which defines the
antigen D and the other one encodes the antigens
called C and E. Now C and E can be important,
but for the purposes of this lecture,
I am just going to focus on D, which is the
major important antigen within the rhesus system.
Now 85% of people, the majority of the population have
the D allele, we call that Rhesus positive (Rh positive).
Whereas the rest are rhesus negative, 15% of us
are rhesus negative (Rh negative).
If you infuse Rh positive blood into a Rh negative person,
they will make antibodies against the rhesus protein.
Now that can be difficult, but it takes a few
days for those antibodies to be made.
So you probably wouldn't notice anything immediately.
The patient may after a week perhaps drop their haemoglobin
or perhaps becomes slightly jaundiced because
they break down the red cell product,
but is not usually an acute problem.
The major problem with the rhesus system
is Haemolytic Disease of the Newborn and this happens when
a mother is Rh-negative, but her baby is Rh-positive.
That means that the rhesus positive gene has
come from the father and here
the mother can be sensitized to the baby's cells and
make antibodies which cross the placenta.
This is classic hemolytic disease of the newborn.
Now on the right, you'll see how very significant
hemolytic disease of the newborn has been
over the last few decades.
On the X-axis is "time" and in the 1950s, you'll see that
the death rate from hemolytic disease of the newborn
approached 1.6 in every thousand births,
really very high indeed.
And then you will see a number of procedures,
which we used to try and control
hemolytic disease of the newborn. At that time:
exchange transfusions, later on amniocentesis - the testing,
intrauterine transfusions. But then in the late 60s,
the thing that made the big difference, the use of
immunoglobulin prophylaxis - giving an anti-D antibody
to mothers after pregnancy if they were sensitized
to Rh-positive cells to stop their own
production of antibodies, very interesting.
And now you can see that this problem is largely controlled.
So when you give or you are planning to give blood
from a donor to a recipient, it must be crossmatched.
How is this done? If a patient needs blood, blood is taken
from them and we determine ABO and rhesus status.
We will also see if they are making any antibodies
against other red cell proteins,
of which there are many potential types.
The donated red cell also has its ABO and rhesus status
determined and has antibody screening done,
and then the correct units can be selected for donation.
But we also mix the serum from the patient with the red
cells that are going to go in in the form of a crossmatch
just to check that the blood has been chosen correctly
and there is no unusual reaction.
On the right, I am showing two different techniques
that were used for crossmatching blood
and for determining the blood group of a patient.
In the top is a 96-well plate and you will see those red
circles, those are where red cells are, within each well
and where each well is broadly red, the red cells have
not aggluttinated, they have not clumped
Whereas you will see on the right-hand side, on some of
those rows of little red dots, that is where
the red cells have agglutinated - that's the positive
cross-reaction which has brought those red cells down.
But now most laboratories have moved using a gel-based
system as you shall see on the bottom
and here these gels have antibodies
against each of the major blood groups.
The blood is put in, centrifuged and you can
see immediately the blood group of the patient.
So on the right-hand side, you will see that
the gel has a Kell test - the K test column,
and the blood has gone straight down and that patient
is K-negative. The antibody did not react to K.
whereas, on the left-hand side, you will see that in the
column B and Rhesus, the cells have remained higher.
The antibody has reacted with that donated blood and
we can group that patient as B and Rh-positive.
So this has very much simplified
the blood group analysis.