Lived 1868 — 1943.

Karl Landsteiner revolutionized medicine when, in 1900-1901,

he identified three major human blood types: A, B, and O,
which led to safe blood transfusions and millions of lives saved.
He also suggested the use of blood types to assist in police
enquiries. Thirty years later, he was awarded the Nobel Prize in
Physiology or Medicine for his discovery of the ABO blood
group system.
 Blood Groups
Introduction

When blood transfusions from one person to another were first

attempted

Immediate or delayed agglutination and hemolysis of the red
blood cells often occurred

Resulted in typical transfusion reactions that frequently led to
death

Soon it was discovered that the bloods of different people have
different antigenic and immune properties

Plasma of one blood will react with red cells of another blood type
Agglutinogens:

Refer to the presence of antigens on the surface of the RBC’s

Agglutinins:

Presence of antibodies against the antigens & are present in the

plasma

Agglutination

Occurs because of the presence of the antigens in the presence

of suitable agglutinins

At least 30 commonly occurring antigens and hundreds of other
rare antigens have been found

Most of the rare antigens are weak
Are of importance principally for studying the inheritance of genes
to establish parentage

Landsteiner’s Law:

This law has two parts:

1. If an agglutinogen is present on the membrane of the RBC,the

corresponding agglutinin is absent in the plasma

2. If an agglutinogen is absent on the membrane of the RBC,the

corresponding agglutinin is present in the plasma

First part of the law is a logical outcome of the situation-cells
would be agglutinated in presence of both agglutinogen &
agglutinin
 The second part is a fact but not a necessary sequence

Rh,MNS systems do not obey the second part of the law

Blood Groups :

Major {O-A-B Type} & Minor {MNS & P Type}

A and B Antigens-Agglutinogens

Two antigens-type A and type B-occur on the surfaces of the red
blood cells in a large proportion of human beings

It is these antigens that cause most blood transfusion reactions

Because of the way these agglutinogens are inherited

People may have neither of them on their cells may have
one, or they may have both simultaneously

Genotypes Blood Types Agglutinogens Agglutinins

Anti –A &
OO O _______ Anti –B

OA or AA A A Anti-B

OB or BB B B Anti-A

AB AB AB ______
Genetic Determination of the Agglutinogens

Two genes, one on each of two paired chromosomes, determine

the O-A-B blood type

These genes can be any one of three types but only one type on
each of the two chromosomes: type O, type A, or type B

The type O gene is either functionless or almost functionless, so
that it causes no significant type O agglutinogen on the cells

Conversely, the type A and type B genes do cause strong
agglutinogens on the cells

The six possible combinations of genes are OO, OA, OB, AA, BB,
and AB
These combinations of genes are known as the genotypes, and
each person is one of the six genotypes

Relative Frequencies of the Different Blood Types

Blood Group India [in %] W.Europe [in %]

A 20 42

B 40 09

AB 08 03

O 32 46
Some Eastern European people show a higher proportion of
Group B [upto 40%]

Pure American Indians belong almost exclusively to Group O

Group A [& AB] is sub-divided further into 2 sub-types : A1 & A2
forming 75 % & 25 % of the population respectively

A & B are called group specific substances & chemically polysa-
ccharides

Rh Blood Types

Along with the O-A-B blood type system, the Rh blood type
system is also important when transfusing blood
Alexander Wiener, US
haematologist
Rh Antigens-"Rh-Positive" and "Rh-Negative" People

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 does not have the c antigen, but
the person missing the C antigen always has the c antigen

The same is true for the D-d and E-e antigens

Because of the manner of inheritance of these factors, each
person has one of each of the three pairs of antigens

The type D antigen is widely prevalent in the population and
considerably more antigenic than the other Rh antigens
Anyone who has this type of antigen is said to be Rh positive,
whereas a person who does not have type D antigen is said to be
Rh negative

About 85 per cent of all white people are Rh positive and 15 per
cent, Rh negative

In American blacks, the percentage of Rh-positives is about 95,
whereas in African blacks, it is virtually 100 per cent

These antigens are integral membrane proteins & not found in
other tissues like ABO systems

Rh Immune Response

Formation of Anti-Rh Agglutinins

In the Rh system, spontaneous agglutinins almost never occur

When red blood cells containing Rh factor are injected into a
person whose blood does not contain the Rh factor

Anti-Rh agglutinins develop slowly, reaching maximum
concentration of agglutinins about 2 to 4 months later

A delayed transfusion reaction occurs, although it is usually mild

On subsequent transfusion of Rh-positive blood into the same
person, who is now already immunized against the Rh factor

The transfusion reaction is greatly enhanced and can be
immediate and severe

This immune response occurs to a much greater extent in some
people than in others

With multiple exposures to the Rh factor, an Rh-negative person
 Eventually becomes strongly "sensitized" to Rh factor

These are of the IgG type & can cross the placenta

Erythroblastosis Fetalis ("Hemolytic Disease of the Newborn")

Erythroblastosis fetalis is a disease of the fetus and newborn child


Characterized by agglutination and phagocytosis of the fetus's red
blood cells

In most instances of erythroblastosis fetalis, the mother is Rh
negative and the father Rh positive

The baby has inherited the Rh-positive antigen from the father

The mother develops anti-Rh agglutinins from exposure to the
fetus's Rh antigen
 
At the time of delivery the fetal RBC’s enter the maternal
circulation severance of the umbilical cord & mixing of fetal &
maternal blood

The mother's agglutinins diffuse through the placenta into the
fetus and cause red blood cell agglutination

The first child escapes the disease

Incidence of the Disease

An Rh-negative mother having her first Rh-positive child usually

does not develop sufficient anti-Rh agglutinins to cause any harm

However, about 3 per cent of second Rh-positive babies exhibit
some signs of erythroblastosis fetalis

About 10 per cent of third babies exhibit the disease; and the
incidence rises progressively with subsequent pregnancies

Effect of the Mother's Antibodies on the Fetus

After anti-Rh antibodies have formed in the mother, they diffuse

slowly through the placental membrane into the fetus's blood

There they cause agglutination of the fetus's blood

The agglutinated red blood cells subsequently hemolyze & release
hemoglobin into the blood

The fetus's macrophages then convert the hemoglobin into
bilirubin & causes the baby's skin to become yellow (jaundiced)

The antibodies can also attack and damage other cells of the
body.
Clinical Picture of Erythroblastosis

The jaundiced, erythroblastotic newborn baby is usually anemic at

birth

The anti-Rh agglutinins from the mother usually circulate in the
infant's blood for 1 to 2 months after birth

Destroy more and more red blood cells

The hematopoietic tissues of the infant attempt to replace the
hemolyzed red blood cells

The liver and spleen become greatly enlarged and produce red
blood cells

In the same manner that they normally do during the middle of
gestation
Because of the rapid production of red cells, many early forms of
red blood cells

Nucleated blastic forms are passed from the baby's bone marrow
into the circulatory system

It is because of the presence of these nucleated blastic red blood
cells that the disease is called erythroblastosis fetalis.

The severe anemia of erythroblastosis fetalis is usually the cause
of death

Many children who barely survive the anemia exhibit permanent
mental impairment or damage to motor areas of the brain

Because of precipitation of bilirubin in the neuronal cells, causing
destruction ,a condition called kernicterus.
Treatment of the Erythroblastotic Neonate

One treatment for erythroblastosis fetalis is to replace the

neonate's blood with Rh-negative blood

About 400 milliliters of Rh-negative blood is infused over a period
of 1.5 or more hours

While the neonate's own Rh-positive blood is being removed

This procedure may be repeated several times during the first few
weeks of life

Mainly to keep the bilirubin level low and thereby prevent
kernicterus

These transfused Rh-negative cells are replaced with the infant's
own Rh-positive cells
Requires 6 or more weeks & by this time the anti-Rh agglutinins
that had come from the mother will have been destroyed

Prevention of Erythroblastosis Fetalis

An Rh immunoglobulin globin, an anti-D antibody is administered

to the expectant mother starting at 28 to 30 weeks of gestation

The anti-D antibody is also administered to Rh-negative women
who deliver Rh-positive babies to prevent sensitization of the
mothers to the D antigen

This greatly reduces the risk of developing large amounts of D
antibodies during the second pregnancy

The mechanism by which Rh immunoglobulin globin prevents
sensitization of the D antigen is not completely understood
One effect of the anti-D antibody is to inhibit antigen-induced B
lymphocyte antibody production in the expectant mother

The administered anti-D antibody also attaches to D-antigen sites
on Rh-positive fetal red blood cells that may cross the placenta

Enter the circulation of the expectant mother, thereby interfering
with the immune response to the D antigen

Hydrops fetalis

The fetus is severely oedematous & occurs when the anemia is

very severe

Usually there occurs intrauterine death of the fetus or if it is born
prematurely or at term it dies within a few hours
Inheritance of Classical Blood Groups

The agglutinogen are inherited as Mendelian dominant & first

appear in the 6th week of fetal life {O,A & B}

Their concentration is 1/5th the adult level & rises progressively
during puberty & adolescence

Group specific substances are not limited to the RBC’s

Found in many organs like salivary glands & pancreas (+
+),liver,kidney,urine & lungs (+) as well as in semen,testes &
amniotic fluid

They are water soluble & in about 80% of people {secretors}
appear in body fluids

The specific agglutinins appear at about 10 days,peak at 10 years
 & then decline – IgM type

Antigens very similar to A & B are common in the intestinal
bacteria & food to which we are exposed

Only 50 % of new born infants have demonstrable agglutinin that
has filtered across the placenta from the mother

These infants rapidly develop antibodies against those antigens
not present in their own blood

These act best at low temperatures & against well diluted cells
{5-200C} & are called as cold antibodies

Rh antigen is also inherited as a dominant gene {D},absent D is
replaced by “d” inherited from both parents
Transfusion Reactions Resulting from Mismatched Blood Types

If donor blood of one blood type is transfused into a recipient who

has another blood type

Transfusion reaction is likely to occur in which the red blood cells
of the donor blood are agglutinated

It is rare that the transfused blood causes agglutination of the
recipient's cells

The plasma portion of the donor blood immediately becomes
diluted by all the plasma of the recipient

Decreases the titer of the infused agglutinins to a level usually too
low to cause agglutination

The small amount of infused blood does not significantly dilute the
 agglutinins in the recipient's plasma

Therefore, the recipient's agglutinins can still agglutinate the
mismatched donor cells

all transfusion reactions eventually cause either immediate
hemolysis resulting from hemolysins

Later hemolysis resulting from phagocytosis of agglutinated cells

The hemoglobin released from the red cells is then converted by
the phagocytes into bilirubin & excreted in the bile by the liver

The concentration of bilirubin in the body fluids often rises high
enough to cause jaundice

But if liver function is normal, the bile pigment will be excreted into
the intestines by way of the liver bile
Jaundice usually does not appear in an adult person unless more
than 400 milliliters of blood is hemolyzed in less than a day

Acute Kidney Shutdown After Transfusion Reactions

One of the most lethal effects of transfusion reactions is kidney

failure

The kidney shutdown seems to result from three causes:

The antigen-antibody reaction of the transfusion reaction releases
toxic substances from the hemolyzing blood that cause powerful
renal vasoconstriction

Loss of circulating red cells in the recipient & production of toxic
substances from the hemolyzed cells and the immune reaction
causes circulatory shock
The arterial blood pressure falls very low, and renal blood flow and
urine output decrease

If the total amount of free hemoglobin released into the circulating
blood is greater than the quantity that can bind with "haptoglobin"
(a plasma protein that binds small amounts of hemoglobin)

If in excess it leaks through the glomerular membranes into the
kidney tubules

If this amount is still slight, it can be reabsorbed through the
tubular epithelium into the blood and will cause no harm

If it is great, then only a small percentage is reabsorbed

Yet water continues to be reabsorbed, causing the tubular
hemoglobin concentration to rise
The hemoglobin precipitates and blocks many of the kidney
tubules

Clinical Applications of Blood Grouping

• In blood transfusion
• In preventing hemolytic disease of the new born
• In paternity disputes
• In medicolegal cases
• In knowing suscepitibility to diseases
• BOMBAY BLOOD GROUP
• Lack H Gene
• Basic precursor substance cannot be
converted into H substance
• Failure to form A or B antigen