BLOOD GROUPS - II
Ms Veena Shriram
The Rh(D) Antigen:

Rh is the most complex system, with
over 45 antigens

Discovered in 1940 after work on
Rhesus monkeys by Landsteiner &
Wiener.

Subsequently discovered to be
unrelated to monkeys.

85% percent of whites are Dpositive and 15% are D negative;
over 99% of Asians are D-positive.

Rh gene located on short arm of chromosome 1

This is another imp. group to be matched before
transfusion.

Thus there are two major groups of antigens
causing major mismatched blood transfusion
reactions
1) ABO system discovered by Landsteiner in 1900.
2) Rh system discovered by Landsteiner in 1940.

Unlike the antibodies of the ABO system, anti-D
antibodies do not develop without exposure of a
D-negative individual to D-positive red cells by
transfusion or entrance of fetal blood into the
RH AGGLUTINOGENS:

There are 6 known agglutinogens which are called Rh
factors present on the R.B.C membrane: C,D,E and c,d,e.

They are not detected in any other tissues other than RBC.

Inheritance: Each person inherits at least 3 of the above
factors from both groups in various combinations from both
parents. e.g. CDE, cDe, cDE,-----

Agglutinogen D is highly antigenic. Person having D will
be called Rh+ve. irrespective of the fact whether C,E is
present or not as C,E are poor agglutinogens.

Cde, CdE, cde.------Ag D is absent: hence even if C,E are
present, person will be labeled Rh-ve.
RH BLOOD GROUP SYSTEM:

In the Rh system the most imp. antigen is the type D.
This occurs on surface of blood cells.

The 5 most imp. genes are present on 3 diff.
chromosomes
- gene ‘D’ is on first chromosome
- genes ‘C’ and ‘c’ are on the second chromosome
- genes ‘E’ and ‘e’ are on the third chromosome

Rh antigens are present only on the surface of blood
cells.

Production of anti-Rh agglutinins in Rh - ve starts if
Rh +ve antigen gets into his blood
1. Rh -ve mother – Rh +ve baby
2. Rh -person – Rh +ve transfusion. (malpractice!!!)

Rh agglutinins belong to the IgG type of
antibodies – they diffuse through the placenta – so
they cause agglutination in the foetal blood
-
erythroblastosis foetalis
To prevent this we must give to the mother anti- Rh
IgG antiserum ( D antigen is the strongest antigen)
RH AGGLUTININS
 Person
who has Ag D i.e. Rh+ve has no naturally
occurring agglutinins in the plasma. Hence Rh
system follows first part of LANDSTEINERS LAW.
 However
if a PERSON is Rh -ve and has no
agglutinogen D yet has no agglutinins in his plasma.
 Hence
Rh system fails to obey the second part of
Landsteiner Law.
RH IMMUNE RESPONSE:

Rh-ve blood can be given to a person who is Rh+ve
as it has no agglutinins against D antigen.

However if Rh+ve blood is given to a person who is
Rh-ve, an immune response is seen as the D antigen
is foreign to the recipient. Hence the recipient
develops
immune
antibodies
to
it. Anti
Rh
agglutinins develop slowly within few hours.
Maximum conc. of the antibodies is seen 2-4
months later. Hence no agglutination is seen as by
the time agglutinins are formed, the donor cells are
already destroyed.

However, a 2nd exposure of Rh-ve person to Rh+ve
blood, severe transfusion reaction is seen due to
agglutination of donor erythrocytes with anti Rh
antibodies which had been formed in the plasma
previously.

On multiple exposures to Rh factor, Rh-ve person gets
so sensitized, that transfusion reactions can be massive
similar to ABO incompatibility.
ERYTHROBLASTOSIS FETALIS:

Also called Hemolytic Disease of the Newborn (HDN)
or Icterus Gravis neonatorum.

Cause: It is due to Rh incompatibility when the mother
is Rh-ve and the fetus is Rh+ve. This is possible if the
father is Rh+ve DD/Dd.

If the father is DD all the children are Rh+ve as D is
dominant in nature.

However if the father is Dd, & the mother dd, then there
is 50% chance that the baby will be Rh negative (dd).

Also if both parents are Rh+ve but heterozygous Dd,
there is one in four chance that the baby will be Rh-ve.
ERYTHROBLASTOSIS FETALIS
SENSITIZATION:

Initially the mother gets sensitized to the fetal blood
carrying Rh antigens. Fetal cells enter mother’s blood
at the time of separation of placenta, when the
maternal sinuses are open.

These fetal cells stimulate production of antibodies in
the mother. However, these antibodies cannot harm
the first baby as separation of placenta takes place
after birth of the first baby. The first baby thus
escapes from the incompatibility.
CONTINUED…..

In the second pregnancy, these antibodies which
have been formed in the earlier pregnancy can
diffuse through the placental barrier (IgG) and
and cause agglutination of the fetal R.B.C’s
provided the second baby is Rh+ve.

In reality 3% of the second baby suffers. While in the
third pregnancy, 10% babies suffer. Incidence rises
with each successive pregnancy.

First born baby may be affected if


Mixing of blood in abortions, any intrauterine
manipulations-fetomaternal bleed.

If mother has been sensitized by previous Rh+ve blood
transfusion.
Hence never give Rh+ve blood to a young Rh-ve
female in the reproductive age group as far as
possible

Clinical picture:

Disease is called Hemolytic Disease of the Newborn
because the newborn shows haemolysis due to
maternal antibodies.

Baby looks pale and anaemic.

Haemolysed
blood then
releases
Hb into the
circulation which is then converted into bilirubin by
macrophages.


Icterus Gravis Neonatorum.
Rh antibodies remain in the babies blood for 1-2
months during which more haemolyis takes place.

To make up for this loss, liver and spleen enlarge to
increase rate of erythropoiesis. However due to rapid
rate of production, immature nucleated R.B.Cs enter
circulation and the peripheral blood shows large
nucleated R.B.C. Hence called Erythroblastosis
Fetalis.

Unconjugated bilirubin then gets deposited in the basal
ganglia and cause destruction of the neuronal cells as
the blood brain barrier is not yet developed. Baby then
shows permanent damage to the motor areas and is
mentally retarded.

Conjugation of bilirubin does not take place as liver is
not yet mature. This condition is called Kernicterus.

If the baby does survive above, then the last stage is of
generalized edema due to damage to liver &
hypoprotenemia.- Hydrops Fetalis.
TREATMENT : EXCHANGE TRANSFUSION

Carried out soon after birth

400 ml of Rh negative - ABO compatible blood is
transfused into Rh+ve baby over a period of few
hours. Simultaneously Rh+ve blood is removed
from the other hand. This procedure is repeated
several times in the first few weeks of life.

Principle: Rh-ve blood is not agglutinated by
antibodies present in the fetus and hence can
tide over the period in which antibodies are
c

i
r
c
u
l
a
t
i
n
g
.
Baby's blood containing antibodies and
bilirubin is removed hence the baby is saved
f r o m

c o m p l i c a t i o n s .
After a few weeks when almost no antibodies
are present, baby's own marrow produces
Rh+ve blood which is now safe.
PREVENTION:

Avoid giving Rh+ve blood to a young Rh-ve female in
the reproductive age group.

Single dose Injection Anti D is given to the mother
within 72 hours of delivery so that these antibodies will
agglutinate the fetal cells circulating in the maternal
blood & they are removed before they can sensitize the
mother.

Gap between 2 pregnancies so that antibody titers are
low.
IMPORTANCE OF BLOOD
GROUPS:

Blood transfusions

Rh blood typing to avoid Erythroblastosis Fetalis.

Paternity Tests. Can rule out paternity not confirm it

Forensic Medicine to identify criminals

Anthropological studies to understand the racial
differences and the evolution of blood Groups.

Correlation between blood groups and disease: e.g.
Blood group O is prone to duodenal ulcer, Blood
Group A is prone to gastric malignancy, pernicious
anemia.
BLOOD TRANSFUSION:

Indications: Severe anemia, hemorrhagic shock
due to wounds, accidents, maternal hemorrhage.

Procedure: Blood is collected from a healthy
Donor.
It is then stored at 40C in a bag containing ACD
(Acid Citrate Dextrose) / CPD (Citrate Phosphate
Dextrose) which act as anticoagulants & can be
HAZARDS OF BLOOD TRANSFUSION:

Due to immune transfusion
reactions:
A) Hemolytic

transfusion reaction:
Major mismatch leads to agglutination of
Donor RBC’s. Activation of complement
system leads to sudden haemolysis and
release of Hb into circulation.

Acute renal shutdown (causes):
1)
Release of toxic substances during hemolytic
reaction causes powerful renal vasoconstriction .
2)
Toxic substances and the loss of RBC’s makes a
person go into circulatory shock. Blood pressure
falls with reduced renal blood flow and urine
output.
3)
Also free Hb which is not bound to haptoglobulin
blocks renal tubules causing acute renal
shutdown.-fatal

1.
Nonhaemolytic immune reaction:
Fever with chills due to allergic reaction to donors
plasma or ACD bag
2.
Anaphylactic reaction due to release of histamine
from donors basophils

Nonimmune transfusion reaction:
1.
circulatory overload & cardiac failure due to rapid
transfusion
stored blood transfusion reaction
2.
a)
ACD causes chelation of Calcium leading to tetany.
b)
Haemolysed RBC release K+ and increased plasma
levels i.e. hyperkalemia is seen especially if the
blood is more than 14 days old.

mild thrombocytopenia because platelets and
clotting factors do not survive in stored blood

Last but not the least, infections transmitted via
blood
are viral hepatitis, HIV, malaria etc.
TRANSPLANTATION OF TISSUES AND ORGANS
 Antigens
of red blood cells that cause
transfusion reactions are also present in
other cells of the body, and each bodily tissue
has
its
own
additional
complement
of
antigens.
 Consequently,
foreign
cells
transplanted
anywhere into the body of a recipient can
produce immune reactions.
AUTOGRAFTS, ISOGRAFTS, ALLOGRAFTS, AND
XENOGRAFTS.

A transplant of a tissue or whole organ from one part
of the same animal to another part is called an
autograft;


from one identical twin to another, an isograft;
from one human being to another or from any
animal to another animal of the same species, an
allograft;

And from a lower animal to a human being or from
an animal of one species to one of another species,
a xenograft.
TRANSPLANTATION OF CELLULAR TISSUES.

In the case of autografts and isografts, cells in the
transplant contain virtually the same types of antigens
to live normally and indefinitely if an adequate blood
supply is provided.

At the other extreme, in the case of xenografts, immune
reactions almost always occur, causing death of the
cells in the graft within 1 day to 5 weeks after
transplantation unless some specific therapy is used to
prevent the immune reactions.

Different cellular tissues and organs that have
been transplanted as allografts: are skin, kidney,
heart, liver, glandular tissue, bone marrow, and
lung. With proper "matching" of tissues between
persons, many kidney allografts have been
successful for at least 5 to 15 years, and
allograft liver and heart transplants for 1 to 15
years.


Describe the molecular basis of blood groups and
the reasons for transfusion reactions.
Short Notes:
1.
Classify blood group
2.
ABO blood group system
3.
Rh factor
4.
Indication of blood transfusion
5.
Mismatched blood transfusion