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7/30/2019 5. ABO Grouping
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6-May-13 1
BLOOD GROUPS
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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 a.g that
are regulated either by allelic genes orclosely 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 antigensABO A1,A2,B,H,A3,Am,AxMNSs M,N,S,s,U,Mg,Mia,Hu,HeMta,Vw,M2,N2,S2P P1,p
k,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 Di
a
,Di
b
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 thesea.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 carefullyabsorbed with human red cells to establish
specificity.
Recently developed a.g specific monoclonala.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 bloodtransfusions 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 individual1.Linked genes
2.Interaction with other genes
3.Loci of blood groups genes onchromosomes (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 4Xg X
Sc 1
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ABO SYSTEM
a. Historical notesIn 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-Aserum 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
A2
AA1
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, B1, 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 (A1A1, A2 O, A1A2). Group A2can 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.
F il 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
on red cell
Antibodies in
plasma
OA
B
AB
OOAA or AO
BB or BO
AB
OA
B
AB
Anti-A, Anti-BAnti-B
Anti-A
None
Fig 2 Synthesis of ABH antigens
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Fig.2 Synthesis of ABH antigens
R
glc gal glcnac galH precursor
Hh gen
fucR
glc gal glcnac gal H antigen
A gene B gene
fuc fucR R
glc gal glcnac gal glcnac glc gal glcnac gal gal
A antigen B antigen
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H antigen
The surfaces oligosaccharides thatconstitutes 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 variantBombay, 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 Legene
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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
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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 Dantigen, also called Rh or Rh factor
Rhesus negative absence of D but
doesnt denote absence of other a.gof 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 toRh +
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 r1CDE Rz
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Other clinically significant systems
1. Kell system
The Kell a.g system rivals the Rh system in itscomplexity 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-activeincomplete 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 causedby 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 Xchromosome. Its not clinically significant but
is of interest as a marker for X chromosome
that appear to escape inactivation by theLyon 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 YesDuffy Occasional Yes
Kidd Occasional Yes
Lutheran Rare No
Lewis Occasional NoP 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 typedand crossmatched to establish ABO and
D compatibility
2. Hemolytic disease of the newborn
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B. In geneticschromosome mapping
C. In forensic medicine :
1. Identification studies
2. Paternity testing
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Thank you