BLOOD GROUPS

Mansyur Arif
Dept. of Clinical Pathology, Faculty of
Medicine, Hasanuddin University /
Dr. Wahidin Sudirohusodo Hospital
Makassar
11-Jan-20 1
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 a.g that
are regulated either by allelic genes or
closely linked genes.

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The number or red cell blood groups now exceeds 400.
(table1).
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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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 hemolysins 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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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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 Thank you

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