The ABO Blood

Group System
Chapter 6
Introduction
The ABO Blood Group System is the most
important blood group system in human
blood transfusion.
It is the only blood group system in which
individuals already have antibodies in their
serum to antigens that are absent from their
red blood cells (RBCs) without any prior
exposure to RBCs through transfusion or
pregnancy.
 History
Karl Landsteiner discovered
the ABO Blood Group
System in 1901
Adriano Sturli and Alfred von
Decastello who were
working under Landsteiner
discovered type AB year
later in 1902
Forward Grouping
determines antigens on patient’s or
donor’s cells.
using known sources of commercial
antisera (anti-A, anti-B) to detect
antigens on an individual’s RBCs.

Reverse grouping
determines antibodies on patient’s or
donor’s cells.
defined as detecting ABO antibodies in
the patient’s serum by using known
reagent RBCs, namely A1 and B cells.
ABO Antibodies
There are two principles:
1. Almost all normal healthy individuals above 3-6 months
of age have "naturally occurring Antibodies" to the ABO
Antigens that they lack
These Antibodies termed naturally occurring because
they were thought to arise without antigenic
stimulation.
2. These "naturally occurring” Antibodies are mostly IgM
class.
That means that, they are antibodies capable of
agglutinating saline/ low protein suspended red cell
without enhancement and may activate complement
cascade.
Inheritance of the ABO Blood Groups

Codominant Inheritance
One position on chromosome 9 is occupied by an A,B O gene
(there are 2 alleles for each gene)
O gene is an amorph
O phenotype is an autosomal recessive
Formation of A, B, and H Red Blood
Cell Antigens

Formation of the A,B and H antigens come from genes at three

separate loci
These genes code for the production of the enzyme that makes
each antigen
The antigens all start from a common glycan
The enzyme determines which final sugar is added to the glycan
and determines the ABO phenotype
Interaction of Hh and ABO Genes
 Molecular Genetics of ABO
Since the cloning in 1990 of the complementary DNA
corresponding to messenger RNA transcribed at the blood group
ABO locus, more than 250 ABO alleles have been identified by
molecular investigation.
All ABO antigens arise from mutations in the single ABO genes.
The presence or absence of the A, B, and H antigens is controlled
by the H and ABO genes.
The presence or absence of ABH antigens on the RBC
membrane is controlled by the H gene.
The presence or absence of ABH antigens in the secretions is
indirectly controlled by Se gene.
 Formation of A, B, and H
Soluble Antigens
ABH antigens are integral parts of the membranes of
RBCs, endothelial cells, platelets, lymphocytes, and
epithelial cells.
Their presence is dependent on the ABO genes
inherited and on the inheritance of another set of
genes called “Sese” that regulates their formation.
Formation of A and B Antigen
 ABO Subgroups

Differ in the amount of antigen present on RBC

membrane.
Have less antigen
Subgroups are the result of less effective enzymes.
(glycosyltranferase)
They are not as efficient in converting H antigen to A
or B antigens.
 A Subgroups
In 1911, von Dungern described two different A
antigens based on reactions between group A RBCs
and anti-A and antiA1.
Group A RBCs that react with both anti-A and anti-A1
are classified as A1.
Those that react with anti-A and not anti-A1 are
classified as A2.
More common than B subgroups.
 A Subgroups
are phenotypes that differ from the others of the same
ABO group with respect to the amount of A antigen
carried on RBCs and in secretors present in saliva.
80% of group A or (AB) individuals are A1 or (A1B)
Approximately 20% are A2 or (A2B)
A1 have 4-6 times the number of antigen sites on the
rbc surface than A2.
A1 is very potent that creates many antigen sites on the
adult RBC, as compared to A2.
 A Subgroups
Why is the A2 phenotype important?
A2 and A2B individual may produce anti-A1.
This may cause discrepancies when a crossmatch is
done.
Differences between A1 and A2 antigen
its quantitative
The A1 gene doesn’t convert the H3 and H4 to A very
well.
The result is fewer A2 antigen sites compared to
many A1 antigen sites.
 A Subgroups
A2 or (A2B) - produce anti-A1
Anti A1 - naturally occuring IgM (cold reacting
antibody)
it is only considered to be clinically significant if it is
reactive at 37C

Group B serum contains anti-A and anti-A1

reacts both with A1 and A2 rbcs
Weak A subgroups
Weak B subgroups
The Bombay Phenotypes (O)
 ABH Antigens and Antibodies in Disease

Various disease states seem to alter RBC antigens, resulting

in either progressively weaker reactions or additional
acquired pseudoantigens, which can be seen during forward
grouping.
Leukemia, chromosome 9 translocation and any hemolytic
diesease.
Hodgkin's disease
Hypogamma globulinemia
ABO Discrepancies

ABO discrepancies occur when unexpected

reactions are obtained in the forward
and/or reverse grouping.
The unexpected reactions may be due to an
extra positive reaction or a weak or missing
reaction in the forward and reverse
grouping.
Technical Errors
Resolution
 Are associated with unexpected
reactions in the reverse grouping due
to weakly reacting or missing
antibodies.
Group I More common.
Discrepancies When a reaction in the serum
grouping is weak or missing, a group
I discrepancy should be suspected
because, normally, RBC and serum
grouping reactions are very strong
(4+).
 • Newborns (ABO antibody production is not detectable
until 3 to 6 months of age)
• Elderly patients (production of ABO antibodies is
depressed)
• Patients with a leukemia (e.g., chronic lymphocytic
Group I leukemia) or lymphoma (e.g., malignant lymphoma)
Discrepancies demonstrating hypogammaglobulinemia
• Patients using immunosuppressive drugs that yield
hypogammaglobulinemia
• Patients with congenital or acquired agammaglobulinemia
or immunodeficiency diseases
 Patients with bone marrow or hematopoietic progenitor stem cell
(HPC) transplants (patients develop hypogam- maglobulinemia
from therapy and start producing a different RBC population
from that of the transplanted bone marrow)
Group I
Patients whose existing ABO antibodies may have been diluted
Discrepancies by plasma transfusion or exchange transfusion
ABO subgroups
Resolution of Common Group I Discrepancies
•

ABO
Discrepancies
Chimerism is defined as the presence
of two cell populations in a single
individual (Table 6–17). It was
discovered in twins born to a group O
mother and group B father with a
mixture of both B and O cell instead of
the expected group of either B or O.

True chimerism occurs only in twins

and is rarely
found.
Major ABO incompatibility occurs
when the donor’s red RBCs are
incompatible with the recipient’s plasma
(e.g., the donor is group B and the
recipient is group O with naturally
occurring anti-B).

Minor ABO incompatibility occurs when

the donor’s plasma is incompatible with
the recipient’s RBCs (e.g., the donor is
group O with naturally occurring anti-B
and the recipient is group B).

Bidirectional ABO incompatibility

occurs when both a major and minor
incompatibility are present (e.g., the
donor is group A and
the recipient is group B).
 Are associated with unexpected
reactions in the forward
grouping due to weakly reacting
Group II
or missing antigens.
Discrepancies
This group of discrepancies is
probably the least frequently
encountered.
 Discrepancies between forward and
reverse blood groupings are caused by
protein or plasma abnormalities,
leading to rouleaux formation or
Group III pseudoagglutination.
Discrepancies
These abnormalities can be seen in
conditions such as multiple myeloma,
Waldenström’s macroglobulinemia,
plasma cell dyscrasias, and Hodgkin’s
lymphomas.
 Group IV ABO Discrepancies

Occurs in the forward and/or reverse groupings due to miscellaneous problems.

Common Etiologies:

1. Cold reactive autoantibodies

2. Circulating RBCs of more than one ABO group due to RBC transfusion or
marrow/stem cell transplant
3. Unexpected ABO isoagglutinins
4. Unexpected non-ABO alloantibodies
 Rare Group IV
Discrepancies

Antibodies other than anti-A and

anti-B may react to form antigen-
antibody complexes that may then
absorb onto patient’s RBCs.

Cis-AB - inheritance of both AB

genes from one parent carried on
one chromosome and an O gene
inherited from the other parent.