BLOOD GROUPS

Presented by:
Dr.Agus Alim Abdullah,SpPK(K)
Clinical Pathologist – Hematology Consultant

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 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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• 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 A1,A2,B,H,A3,Am,Ax
MNSs M,N,S,s,U,Mg,Mia,Hu,HeMta,Vw,M2,N2,S2
P P1,pk,P2,(Tja)
Rh D,C,E,c,e,Cw,Ew,ce,Ce,G,CE,cE,Du,Cu,Eu,LW
Lutheran Lua,Lub
Kell K,k,Kpa,Kpb,Jsa,Jsb
Lewis Lea,Leb
Wright Wra,Wrb
Diego Dia,Dib
Cartwright Yta,Ytb
Xg Xga
Dombrock Doa,Dob
Colton Coa,Cob

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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
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found in certain ethnic groups 10
• 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 Genotype
A AA or AO
B BB or BO
AB AB
O OO
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Rh blood group system
• The Rh system is the second most significant
blood-group 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
Recipient Donor
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

O Y Y Y Y

A Y Y

B Y Y

AB 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 anti-
A, 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.,anti-
globulin 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 Chromosome
ABO 9
Rh 1
Fy 1
Chido, Rogers 6
MNSs 4
Xg X
Sc 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 None Anti-A and Anti-B
A A Anti-B
B B Anti-A
AB A and B 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 Reaction with

Anti-A Anti-A1
A1 AA1 + +
A2 A + -

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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 B A1
Genotype BO A1O

Phenotype O O A1B
Genotype OO OO A1B

Family 2

Phenotype A1 A2B
Genotype A1A2 A2B

Phenotype A2B A1
Genotype A2B A1A2

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 Antibodies in

on red cell plasma

O OO O Anti-A, Anti-B
A AA or AO A Anti-B
B BB or BO B Anti-A
AB AB AB 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 H antigen

A gene B gene

fuc fuc
R R

glc gal glcnac gal glcnac glc gal glcnac gal gal
A antigen B antigen
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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 doesn’t
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 can’t 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 (Gal-
Gal-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
doesn’t denote absence of other a.g
of the Rh system (C,c,E or e)

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

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Table 6. Rh gene complexes
Fischer-Race Wiener
CDe R1
cde r
cDE R2
cDe Ro
CwDe R1W
cdE ru
Cde r1
CDE 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 Duffy-
sensitive 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. It’s 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 Cause of HDN
ABO Very common Yes
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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 Thank you

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