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BLOOD GROUPS

Mansyur Arif
Bag. Patologi Klinik FK UNHAS / RSUP
Dr. Wahidin Sudirohusodo
Dec 10, 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 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
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

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.,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

A1

Genotype

A2B
A 1A2

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

glcnac gal
A antigen

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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

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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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