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BLOOD GROUPS

Mansyur Arif
Bag. Patologi Klinik FK UNHAS / RSUP
Dr. Wahidin Sudirohusodo
Sep 26, 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
g
a
a
M,N,S,s,U,M ,Mi ,Hu,HeMt ,Vw,M2,N2,S2
k
a
P1,p ,P2,(Tj )
w
w
u
u
u
D,C,E,c,e,C ,E ,ce,Ce,G,CE,cE,D ,C ,E ,LW
a
b
Lu ,Lu
a
b
a
b
K,k,Kp ,Kp ,Js ,Js
a
b
Le ,Le
a
b
Wr ,Wr
a
b
Di ,Di
a
b
Yt ,Yt
a
Xg
a
b
Do ,Do
a
b
Co ,Co
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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
A
B
AB

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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 &
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 10 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

BO

Phenotype

Genotype

OO

A1
A1O

A1B

OO

A1B

Family 2

Phenotype

A1

A2B

Genotype

A1A2

Phenotype

A2B

Genotype

A2B A1A2

A2B

A1

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
H precursor

glcnac

gal

Hh gen

R
glc

fuc
gal

A gene

R
glc

gal

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glcnac

galH antigen

B gene
fuc

glcnac gal glcnac


A antigen
B antigen

fuc
glc

gal

glcnac

gal

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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21

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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2. Weiner system
3. Rosenfield system
B. Compound antigens
C. Weakened antigens :
- weakly reactive ag D

- formal terminology : Rh , D variant


+

- for transfusion : D is equivalent to Rh


u

D. Deleted antigens : Rh null cells.


E. Rh antigens structure
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Table 6. Rh gene complexes


Fischer-Race
CDe
cde
cDE
cDe
w
C De
cdE
Cde
CDE
Sep 26, 2016

Wiener

R
r
2
R
o
R
1W
R
u
r
1
r
z
R
1

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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,
a
b
a
b
Kp -Kp and Js -Js
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, Lu and Lu and a
silent one. The double-negative phenotype caused
by either dominant inhibitor gene or a recessive
silent allele.
a

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5. Xg blood group
a

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

Cause of HDN

ABO
Very common Yes
Rh Common Yes
KellOccasional Yes
Duffy
Occasional Yes
Kidd
Occasional Yes
Lutheran RareNo
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 &
crossmatched to establish ABO & 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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