BLOOD GROUPS

Presented by:

Dr.Agus Alim Abdullah,SpPK(K)

Clinical Pathologist Hematology Consultant

Nov 14, 2016

Definitions
Blood groups are determined by antigens
structures on the surfaces or red cells and
are detected by reactions with specific
antibodies.
A blood group system is defined by
antigens that are regulated either by allelic
genes or closely linked genes.
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Nov 14, 2016

 A blood type (also called a blood group) is

a classification of blood based on the
presence or absence of inherited antigenic
substances on the surface of red blood cells
(RBCs).
These antigens may be proteins,
carbohydrates, glycoproteins, or glycolipids
, depending on the blood group system.
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 Some of these antigens are also present on the

surface of other types of cells of various tissues.
Several of these red blood cell surface antigens
that stem from one allele (or very closely linked
genes), collectively form a blood group system.
Blood types are inherited and represent
contributions from both parents. A total of 30
human blood group systems are now recognized
by the International Society of Blood Transfusion
(ISBT)
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 Many pregnant women carry a fetus with a different

blood type from their own, and the mother can form
antibodies against fetal RBCs.
Sometimes these maternal antibodies are IgG, a
small immunoglobulin, which can cross the placenta
and cause hemolysis of fetal RBCs, which in turn
can lead to hemolytic disease of the newborn, an
illness of low fetal blood counts that ranges from
mild to severe
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Uses of blood grouping data

A. In clinical medicine
1. Pretransfusion testing :
Prior to transfusion, blood is typed
and crossmatched to establish ABO and
D compatibility
2. Hemolytic disease of the newborn

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B. In genetics chromosome mapping

C. In forensic medicine :
1. Identification studies
2. Paternity testing

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The number or red cell blood groups now exceeds 400 (tab 1).
Table 1. Survey of major Red Cell Blood Group System
System
Important antigens
ABO
MNSs
P
Rh
Lutheran
Kell
Lewis
Wright
Diego
Cartwright
Xg
Dombrock
Colton
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A1,A2,B,H,A3,Am,Ax
M,N,S,s,U,Mg,Mia,Hu,HeMta,Vw,M2,N2,S2
P1,pk,P2,(Tja)
D,C,E,c,e,Cw,Ew,ce,Ce,G,CE,cE,Du,Cu,Eu,LW
Lua,Lub
K,k,Kpa,Kpb,Jsa,Jsb
Lea,Leb
Wra,Wrb
Dia,Dib
Yta,Ytb
Xga
Doa,Dob
Coa,Cob
9

Blood group systems

A complete blood type would describe a full
set of 30 substances on the surface of RBCs,
and an individual's blood type is one of the
many possible combinations of blood-group
antigens.
Across the 30 blood groups, over 600
different blood-group antigens have been
found, but many of these are very rare or are
mainly found in certain ethnic groups
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 Almost always, an individual has the same blood

group for life, but very rarely an individual's blood
type changes through addition or suppression of
an antigen in infection, malignancy, or
autoimmune disease.
An example of this rare phenomenon is the case of
Demi-Lee Brennan, an Australian citizen, whose
blood group changed after a liver transplant.

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 Another more common cause in blood-type

change is a bone marrow transplant. Bone-marrow
transplants are performed for many leukemias and
lymphomas, among other diseases. If a person
receives bone marrow from someone who is a
different ABO type (e.g., a type A patient receives
a type O bone marrow), the patient's blood type
will eventually convert to the donor's type

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 Some blood types are associated with inheritance of

other diseases; for example, the Kell antigen is
sometimes associated with McLeod syndrome.
Certain blood types may affect susceptibility to
infections, an example being the resistance to
specific malaria species seen in individuals lacking
the Duffy antigen.
The Duffy antigen, presumably as a result of
natural selection, is less common in ethnic groups
from areas with a high incidence of malaria
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The ABO system

is the most important blood-group system in
human-blood transfusion. The associated anti-A
antibodies and anti-B antibodies are usually
Immunoglobulin M, abbreviated IgM, antibodies.
ABO IgM antibodies are produced in the first
years of life by sensitization to environmental
substances such as food, bacteria, and viruses. The
O in ABO is often called 0 (zero, or null) in other
languages
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Phenotype
A
B
AB

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Genotype
AA or AO
BB or BO
AB

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Rh blood group system

The Rh system is the second most significant bloodgroup system in human-blood transfusion with
currently 50 antigens.
The most significant Rh antigen is the D antigen
because it is the most likely to provoke an immune
system response of the five main Rh antigens. It is
common for D-negative individuals not to have any
anti-D IgG or IgM antibodies, because anti-D
antibodies are not usually produced by sensitization
against environmental substances
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 However, D-negative individuals can produce IgG anti-D

antibodies following a sensitizing event: possibly a
fetomaternal transfusion of blood from a fetus in pregnancy
or occasionally a blood transfusion with D positive RBCs.
Rh disease can develop in these cases. Rh negative blood
types are much less in proportion of Asian populations
(0.3%) than they are in White (15%).
In the table below, the presence or absence of the Rh
antigens is signified by the + or - sign, so that for example
A- group does not have any of the Rh antigens
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Red blood cell compatibility

Recipien
Donor
t
O
O+ A A+ B B+ AB AB+

O Y
O+ Y Y
A Y
Y
A+ Y Y
Y
Y
B Y
Y
B+ Y Y
Y
Y
AB Y
Y
Y
Y
AB+ Y Y
Y
Y
Y
Y
Y
Y

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 An Rh D-negative patient who does not

have any anti-D antibodies (never being
previously sensitized to D-positive RBCs)
can receive a transfusion of D-positive
blood once, but this would cause
sensitization to the D antigen, and a female
patient would become at risk for hemolytic
disease of the newborn
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 If a D-negative patient has developed anti-D antibodies, a

subsequent exposure to D-positive blood would lead to a
potentially dangerous transfusion reaction. Rh D-positive blood
should never be given to D-negative women of child bearing age
or to patients with D antibodies, so blood banks must conserve
Rh-negative blood for these patients. In extreme circumstances,
such as for a major bleed when stocks of D-negative blood units
are very low at the blood bank, D-positive blood might be given
to D-negative females above child-bearing age or to Rh-negative
males, providing that they did not have anti-D antibodies, to
conserve D-negative blood stock in the blood bank

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 The converse is not true; Rh D-positive patients

do not react to D negative blood. This same
matching is done for other antigens of the Rh
system as C, c, E and e and for other blood
group systems with a known risk for
immunization such as the Kell system in
particular for females of child-bearing age or
patients with known need for many transfusions.
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Plasma compatibility

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Plasma compatibility table

Recipient

Donor

O
A
B
AB
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B AB

Y
Y

Y
Y
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 Rh D antibodies are uncommon, so generally neither D

negative nor D positive blood contain anti-D antibodies. If a
potential donor is found to have anti-D antibodies or any
strong atypical blood group antibody by antibody screening
in the blood bank, they would not be accepted as a donor (or
in some blood banks the blood would be drawn but the
product would need to be appropriately labeled); therefore,
donor blood plasma issued by a blood bank can be selected
to be free of D antibodies and free of other atypical
antibodies, and such donor plasma issued from a blood bank
would be suitable for a recipient who may be D positive or D
negative, as long as blood plasma and the recipient are ABO
compatible
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Universal donors and universal recipients

With regard to transfusions of whole blood or packed red
blood cells, individuals with type O Rh D negative blood are
often called universal donors, and those with type AB Rh D
positive blood are called universal recipients; however, these
terms are only generally true with respect to possible
reactions of the recipient's anti-A and anti-B antibodies to
transfused red blood cells, and also possible sensitization to
Rh D antigens. One exception is individuals with hh antigen
system (also known as the Bombay blood group) who can
only receive blood safely from other hh donors, because
they form antibodies against the H substance
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 Blood donors with particularly strong antiA, anti-B or any atypical blood group
antibody are excluded from blood donation.
The possible reactions of anti-A and anti-B
antibodies present in the transfused blood to
the recipients RBCs need not be considered,
because a relatively small volume of plasma
containing antibodies is transfused
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 By way of example: considering the transfusion of O Rh D

negative blood (universal donor blood) into a recipient of
blood group A Rh D positive, an immune reaction between
the recipient's anti-B antibodies and the transfused RBCs is
not anticipated. However, the relatively small amount of
plasma in the transfused blood contains anti-A antibodies,
which could react with the A antigens on the surface of the
recipients RBCs, but a significant reaction is unlikely
because of the dilution factors. Rh D sensitization is not
anticipated.
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 Additionally, red blood cell surface antigens other

than A, B and Rh D, might cause adverse reactions
and sensitization, if they can bind to the
corresponding antibodies to generate an immune
response. Transfusions are further complicated
because platelets and white blood cells (WBCs)
have their own systems of surface antigens, and
sensitization to platelet or WBC antigens can
occur as a result of transfusion
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 With regard to transfusions of plasma, this

situation is reversed. Type O plasma, containing
both anti-A and anti-B antibodies, can only be
given to O recipients. The antibodies will attack
the antigens on any other blood type. Conversely,
AB plasma can be given to patients of any ABO
blood group due to not containing any anti-A or
anti-B antibodies

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Antibodies : sources & properties

1. Normal humans
A.bodies to some blood group a.g occur in
the serum of individuals who lack the a.g
and have had no prior exposure to it
natural isohemagglutinins.
The major ones are directed against surface
a.g such as the ABO, Ii and P systems
controlled by oligosaccharides
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Isohemagglutinins with ABO are always

clinically significant
Isohemagglutinins elicited by similar
sequences on microbial surfaces >>Ig Ms
effective hemolysis because they efficiently
fix complement.
Occasionally Ig G a.bodies specific for these
a.g also appear.
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2. Immunized animals
If animals are immunized with human red cells
may form a.bodies to certain of the
xenogeneic blood group a.g important
source of blood group anti sera carefully
absorbed with human red cells to establish
specificity.
Recently developed a.g specific monoclonal
a.bodies do not require such absorption.
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3. Immunized humans
The third major source of the blood group anti
bodies are donors who have been
allogenically immunized either by (1) prior
blood transfusions or (2) previous pregnancies
immune antibodies elicited by prior
exposure to red cell a.g are commonly IgGs

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Methods of detection
1. Agglutination by specific antibody
Under physiologic conditions of pH and ionic
strength, normal red cells repel each other
owing to their negative surface charge or
zeta potential
2. Enhancement of agglutination by antibody
a. Reduction of zeta potential
Can be reduced by addition of colloid (alb,
polyvinylpyrrolidone or dextran).
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b. Insertion of a.b red cells bridges

Agglutinations may produced or enhanced
by addition of Coomb reagent (i.e.,antiglobulin a.body)
3. Use of lectins
4. Automated techniques

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Genetics

According to Mendelian laws

Heredity is generally autosomal
codominant i.e there is an expression of
both alleles in the heterozygous individual
1. Linked genes
2. Interaction with other genes
3. Loci of blood groups genes on
chromosomes (table 2)
4. Occurrence of blood group antigens
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Table 2. Chromosome Assignment of Some Blood

Group Loci
Locus
ABO
Rh
Fy
Chido, Rogers
MNSs
Xg
Sc
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Chromosome
9
1
1
6
4
X
1
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ABO SYSTEM
a. Historical notes
In subsequent work Landsteiner recognized
that the pattern of reactions could be
explained by two a.g, which designated A
and B. O signified the state of not having A
or B.
Table 3. The Landsteiner scheme

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Table 3. The ABO system defined by Anti-A and Anti B

Blood Groups

Antigens on RC

Antibodies in serum

O
A
B
AB

None
A
B
A and B

Anti-A and Anti-B

Anti-B
Anti-A
None

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b. Subdivisions of A antigen
A antigen and anti-A are complex. Anti-A
serum from a group B donor contains 2 types
of a.b, anti-A and anti-A1 . (table 4)
Group

Antigens

A1

AA1

A2

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Reaction with
Anti-A
Anti-A1
+
+

+
-

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Genetics
Determining the blood group : genotype and
phenotype. A child receives one of four genes
from each parent : A1, A2, B, or O. Six phenotypes
are possible because the A a.g associated with
group A2 and also A1.
There are ten possible genotypes. Group A1 may
have 3 genotypes (A1 A1, A1 O, A1A2). Group A2
can have either A2A2 or A2 O genotypes. Group B
can have either BB or BO genotypes
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 Genotype :
- specific genes that person carries
- determined by family studies
- AA, AO, BB, BO, AB and OO
- see fig 1.

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Family 1

Phenotype
Genotype

B
BO

A1
A1O

Phenotype

A1B

Genotype

OO

OO

A1B

Family 2

Phenotype
Genotype

A1

A2B
A 1A 2

Phenotype

A2B A1

Genotype

A2B A1A2

A 2B

Fig 1. Illustration of usefulness of family studies in the elucidation of phenotype

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Phenotype :
Four phenotypes : A, B, AB and O
Although there are ten possible genotypes,
the absence of a specific anti-O prevents the
serological recognition of more than four
phenotypes. (table 5)

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Table 5. Blood Type

Phenotype

Genotype

Antigens
on red cell

Antibodies in
plasma

O
A
B
AB

OO
AA or AO
BB or BO
AB

O
A
B
AB

Anti-A, Anti-B
Anti-B
Anti-A
None

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Fig.2 Synthesis of ABH antigens

R
glc

gal

glcnac

gal

H precursor

Hh gen

fuc

R
glc

gal

glcnac

gal

A gene
fuc

R
glc

gal

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glcnac gal
A antigen

glcnac

H antigen

B gene
fuc

R
glc

gal

glcnac gal
B antigen

gal
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H antigen
The surfaces oligosaccharides that
constitutes the H a.g is the precursor of the
A and B a.g
Gene A & B responsible for converting H
substance into A & B substance
The O gene is an amorph and doesnt
transform the H substance
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Rare variant Bombay, the H precursor

cannot be converted to H lack H ag &
hence A or B phenotype cant be expressed.
A terminal sugar molecules determine a.g
specificity :
A a.g : N acetylgalactosamine
B a.g : galactosa

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Other Carbohydrate Antigen

a. Lewis system
The Lewis a.g are made from the same
precursors as the ABH a.g except that they
are exclusively type 1 chain.
The expression ag depends on the
interaction of the H gene, Se gene and Le
gene
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b. P system
These ag were recognized by antisera
developed in rabbits glycosphingolipids
and originate on a ceramide dihexose (GalGal-ceramide)
c. Ii system
Most cold a.bodies have specificity against
the Ii a.g system. These a.g are found in red
cells and nonhematopoietic tissue
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Rhesus System

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Rhesus a.b >> immune (previous

transfusion or pregnancy), naturally <<
Anti-D is responsible for most of the clinical
problems associated with the system the
simple subdivision of subjects into Rh D +
and Rh D , using anti-D is sufficient for
routine clinical purposes.

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A. Nomenclature : relation to genetic

models
1. Fischer-Race theory (table 6) :
Postulates 3 closely linked genes Cc,
Dd and Ee. Rhesus a.g is renamed D.
Rhesus positive presence of the D
antigen, also called Rh or Rh factor
Rhesus negative absence of D
but doesnt denote absence of other
a.g of the Rh system (C,c,E or e)
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B.
C.

D.
E.

2. Weiner system
3. Rosenfield system
Compound antigens
Weakened antigens :
- weakly reactive ag Du
- formal terminology : Rh +, Du variant
- for transfusion : Du is equivalent to Rh +
Deleted antigens : Rh null cells.
Rh antigens structure

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Table 6. Rh gene complexes

Fischer-Race
CDe
cde
cDE
cDe
CwDe
cdE
Cde
CDE

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Wiener
R1
r
R2
Ro
R1W
ru
r1
Rz

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Other clinically significant systems

1. Kell system
The Kell a.g system rivals the Rh system in its
complexity and clinical importance. Appearing in
response to prior immunization, anti-Kell a.b have
caused hemolytic transfusion reactions and HDN.
The main a.g pairs : K-k, Kpa-Kpb and Jsa-Jsb
2. Duffy system
Double negative phenotype red cells, Fy (a-b-) are
totally resistant to invasion by Plasmodium vivax.
Transfusion of incompatible blood into Duffysensitive individuals can cause severe hemolysis.
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3. Kidd system
Immunization to Kidd is caused mainly by
transfusions. Kidd a.b are evanescent warm-active
incomplete a.b that may not be detected in red cell
a.b screens. Consequently they often cause
delayed transfusions rx, which may be severe.
4. Lutheran system
There are 2 common alleles, Lua and Lub and a
silent one. The double-negative phenotype caused
by either dominant inhibitor gene or a recessive
silent allele.
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5. Xga blood group

This a.g is controlled by a gene on the X
chromosome. Its not clinically significant but
is of interest as a marker for X chromosome
that appear to escape inactivation by the
Lyon mechanism.

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The ABO and Rhesus (Rh) groups are of major clinical

significance. Some other systems of less overall
importance are listed in table 7.
Systems

Frequency of a.body

ABO
Very common
Rh Common
Yes
Kell Occasional Yes
Duffy
Occasional Yes
Kidd
Occasional Yes
Lutheran Rare No
Lewis
Occasional No
P Occasional Yes (rare)
MN Rare Yes (rare)
Ii Rare No

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Cause of HDN

Yes

59

Thank you

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