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BLOOD GROUP

SYSTEMS
Agaton T. Panopio, Jr., MD, MHPEd

The ABO System

Inheritance
The agglutinogens of the ABO system are genetically determined
and are inherited according to Mendelian laws.
There are three allelic genes inherited:
A, B and O.
Genes A and B are co-dominant (egalitarian); O is recessive.

Inheritance
Genes

Z gene
Regulates activity of the H gene on
the basic precursor on red cells
H gene
Converts the basic precursor to the
H agglutinogen by addition of Lfucose to the terminal galactose

Inheritance
Genes

A gene
Converts the H agglutinogen to the A
agglutinogen by adding N-acetyl
galactosamine to fucose
B gene
Converts the H agglutinogen to the
B agglutinogen by adding D-galactose
to fucose

Inheritance
Genes
O gene

An amorphic gene
Does not give rise to any detectable
gene product
Se gene
Regulates activity of the H gene on
the basic precursor in the body fluids

Inheritance

Inheritance

Inheritance

Inheritance

Inheritance

Inheritance
A, B and H agglutinogens are detectable as early as 37 days of
fetal life.

They are fully developed at birth, except


for the A agglutinogen.
Immunogenicity however is low, and
occurs only at 3-6 months of age.

Agglutinins
Follow Landsteiners Law
In normal healthy adults and in children above the age of 6
months, the serum will contain anti-A agglutinin if the red cell
does not have the A agglutinogen; the serum will contain anti-B
if the red cell does not have the B agglutinogen.

Agglutinins
The agglutinins are naturally occurring in that they result from
unavoidable exposure to group specific substances. They are
of the Ig M variety.

Specific sensitization results in production


of immune agglutinins, and are of the Ig
G variety.

Blood Groups
Agglutinogen
A
B
A and B
H

Agglutinin
anti-B
anti-A
no anti-A,
no anti-B
anti-A, anti-B

Blood Grouping
Forward Typing
Mixing of known typing sera with unknown red cells
Used to identify the agglutinogen
present on red cells

Blood Grouping
Reverse Typing

Mixing of known red cells with unknown


sera
Used to determine the agglutinins in the
serum
Used also to check on the results of
forward typing

Blood Groups
Group

A
B
AB
O

Anti-A

Anti-B

+
+
-

B O
Cells

+
+
-

+
+

+
+

Rh Blood Group System

Inheritance
Landsteiner-Weiner Theory
Landsteiner and Weiner postulate that an individual may inherit
any one of a possible 8 allelic genes from each parent. These
genes are on one locus of each chromosome and are: r, r, r,
ry, Ro, R1, R2 and Rz

Inheritance
Fisher-Race Theory

Fisher and Race postulate that there


are 3 Rh antigens (D, C and E). For
each of these antigens, there exists a
corresponding antithetical antigen (d, c
and e). The 3 pairs of Rh antigens are
determined by 3 pairs of allelic genes
namely: Dd, Cc, and Ee, that are
closely linked in 3 sub-loci.

Antigens
Chemically, the antigens are lipoproteins and form an integral
part of the red cell membrane. The antigen polypeptide is
attached to membrane lipid.
The Rh antigens are found only on red cell membranes. They are
fully developed at birth and are fully immunogenic.

Antigens
Just like the ABO system, the Rh antigens also have a basic
precursor.

Development of this basic precursor


depends on the inheritance of another
gene the X1 gene.
Individuals who are homozygous or
heterozygous for this gene will develop
the basic precursor.

Antigens
Common antigens and their frequency:

e
D
G
c
C
f
E

=
=
=
=
=
=
=

98%
85%
85%
80%
70%
64%
30%

Antigens
In the order of immunogenicity:

D
c
E
C
e

Antibodies
The Rh antibodies are NOT naturally occurring. They only occur
as a result of specific sensitization such as pregnancy,
incompatible blood transfusion, or deliberate immunization via
intravenous injection of incompatible blood.

Rh Grouping
Blood grouping in the Rh system involves forward typing only
since antibodies are not naturally occurring.
There are 3 main typing sera:
anti-D (anti-Rho)
anti-C (anti-rh)
anti-E (anti-rh)

Rh Grouping
Group Anti-D Anti-C Anti-E Anti-c Anti-e

CcDEe
CCDEE
ccDee
CcDEE
CCEE
cde

+
+
+
+
-

+
+
+
+
-

+
+
+
+
-

+
+
+
+

+
+
+

Rh Grouping
Among Filipinos, the incidence of Rh phenotypes is:

cDe = 0%
Cde = 87%
cDE = 2%
CDE = 11%

Problems in Blood Grouping


Newborns and Elderly
Hypogammaglobulinemia or agammaglobulinemia
Subgroups of A; subgroups of B
Diseases:
Leukemia
Hodgkins disease
CA of the stomach and pancreas

Problems in Blood Grouping


Rouleaux formation

Multiple myeloma
Waldenstroms macroglobulinemia
Polyagglutination
Red cells are clumped at room
temperature but not at 37o C

Problems in Blood Grouping


Panagglutination

Bacteriogenic (Hubener-ThomsenFriedenreich phenomenon)


Bacteria uncover a latent
receptor on RBC membrane (T
receptor) and is acted upon by
anti-T present in all normal sera
Reaction is at room temperature

Problems in Blood Grouping


Panagglutination
Non-bacteriogenic

Seen in acquired hemolytic anemia


Positive direct anti-globulin test
Cold agglutinins
React strongly at 4o C

Practical Significance

Blood Transfusion
The purpose of a blood transfusion is to provide some benefit to
the recipient. Thus, blood types of both donor and recipient
must be compatible.
In the Philippines, typing sera of the other blood group systems
are not available. Thus aside from blood typing, compatibility
testing must be done.

Compatibility Testing
Involves:
Review of the recipients past blood
records
ABO and Rh typing of recipient and
Antibody screening of recipients and
Cross-matching

bank history and


donor
donors serum

Cross-Matching
Major cross-match
Mixing of recipients serum with donors

red cells

Minor cross-match
Mixing of donors serum with patients red cells

Cross-Matching
Phases:

Protein phase
Can detect:
ABO incompatibilities
Cold antibodies (anti-M, antiP1, anti-Lea)
Prozoning anti-Rh antibodies

Cross-Matching
Phases:

Thermo phase
Can detect:
Low titer anti-D
Rh antibodies reactive in
albumin (anti-c, antiE,
some anti-D)

Cross-Matching
Phases:
Anti-globulin phase

Can detect:
Cryptagglutinoids
Antibodies reactive only in antiglobulin

Cross-Matching
Antibodies reactive only in anti-globulin:

Anti-Fya (Duffy)
Anti-Jka (Kidd)
Anti-K (Kell)
Anti-Di (Diego)
Anti-Sc1&2 (Scianna)
Anti-Wra&b (Wright)
Anti-Coa&b (Colton)
Anti-Doa&b (Dombrock)

Hemolytic Disease of the Newborn


HDN due to ABO incompatibility
Mother is type O, baby is type A or B
HDN due to Rh incompatibility
Mother is D negative, baby is D positive
Not seen among Filipinos since Filipinos

are all D positive

Maternity/Paternity Exclusion
Five types of paternal exclusion are possible:

The father lacks a factor that is present


in the child and is absent in the
mother
The child lacks both factors present in
the putative father

Maternity/Paternity Exclusion
Five types of paternal exclusion

The child is homozygous for a factor


present in only one of the parents
The child lacks a factor for which the
putative father is homozygous
The genotypes of the mother and
putative father do not match the
genotype of the child

Maternity/Paternity Exclusion
ABO system follows Mendelian laws

First law
Factors A or B cannot be present in
a child unless present in one or both
parents
Second law
A parent of group AB cannot have a
child of group O

Maternity/Paternity Exclusion
Mendelian laws

Third law
A parent of group O cannot have a
child of group AB

Maternity/Paternity Exclusion
Maternal exclusion has become important because of the illegal
practice of baby switching, especially in hospitals abroad.