abo system
DESCRIPTION
Abo Syste,TRANSCRIPT
ABO Blood Group System
History: Karl Landsteiner
Discovered the ABO Blood Group System in 1901
He and his five co-workers began mixing each others red cells and serum together and inadvertently performed the first forward and reverse ABO groupings
Why is it important?
ABO compatibility between donor cell and patient serum is the essential foundation of pretransfusion testing
It is the only system with expected antibodies Whether they are IgG or IgM, ABO antibodies
can activate complement readily This means that incompatibilities can cause life
threatening situations (transfusion reactions)
ABO antigens:
Biochemical & Genetic Considerations
ABO and H Antigen Genetics Genes at three separate loci control the
occurrence and location of ABO antigens
The presence or absence of the A, B, and H antigens is controlled by the H and ABO genes
The presence or absence of the ABH antigens on the red blood cell membrane is controlled by the H gene
The presence or absence of the ABH antigens in secretions is indirectly controlled by the Se gene
ABO Antigen Genetics
H gene – H and h alleles (h is an amorph)
Se gene – Se and se alleles (se is an amorph)
ABO genes – A, B and O alleles
H Antigen
The H gene codes for an enzyme that adds the sugar fucose to the terminal sugar of a precursor substance (PS)
The precursor substance (proteins and lipids) is formed on an oligosaccharide chain (the basic structure)
RBC Precursor Structure
Glucose
Galactose
N-acetylglucosamine
Galactose
Precursor Substance (stays the
same)
RBC
Formation of the H antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
H antigen
RBC
Fucose
H antigen
The H antigen is the foundation upon which A and B antigens are built
A and B genes code for enzymes that add a sugar to the H antigen Immunodominant sugars are present at the
terminal ends of the chains and confer the ABO antigen specificity
A and B Antigen
The “A” gene codes for an enzyme (transferase) that adds N-acetylgalactosamine to the terminal sugar of the H antigen N-acetylgalactosaminyltransferase
The “B” gene codes for an enzyme that adds D-galactose to the terminal sugar of the H antigen D-galactosyltransferase
Formation of the A antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
FucoseN-acetylgalactosamine
Formation of the B antigen
Glucose
Galactose
N-acetylglucosamine
Galactose
RBC
FucoseGalactose
Genetics
The H antigen is found on the RBC when you have the Hh or HH genotype, but NOT from the hh genotype
The A antigen is found on the RBC when you have the Hh, HH, and A/A, A/O, or A/B genotypes
The B antigen is found on the RBC when you have the Hh, HH, and B/B, B/O, or A/B genotypes
H antigen
Certain blood types possess more H antigen than others:
O>A2>B>A2B>A1>A1BGreatest amount of H
Least amount of H
The O allele
Why do Group O individuals have more H antigen than the other groups?
The O gene is a silent allele. It does not alter the structure of the H substance….that means more H antigen sites
Group O Group A
Many H antigen sites
Fewer H antigen
sites
A
A A
AA
Most of the H antigen sites in a Group A individual have been
converted to the A antigen
ABO Antigens in Secretions Secretions include body fluids like plasma,
saliva, synovial fluid, etc
Blood Group Substances are soluble antigens (A, B, and H) that can be found in the secretions.
This is controlled by the H and Se genes
Secretor Status
The secretor gene consists of 2 alleles (Se and se)
The Se gene is responsible for the expression of the H antigen on glycoprotein structures located in body secretions
If the Se allele is inherited as SeSe or Sese, the person is called a “secretor” 80% of the population are secretors
Secretors Secretors express soluble forms of the H
antigen in secretions that can then be converted to A or B antigens (by the transferases)
Individuals who inherit the sese gene are called “nonsecretors” The se allele is an amorph (nothing expressed) sese individuals do not convert antigen precursors
to H antigen and has neither soluble H antigen nor soluble A or B antigens in body fluids
Secretor Status Summary The Se gene codes for the presence of the H
antigen in secretions, therefore the presence of A and/or B antigens in the secretions is contingent on the inheritance of the Se gene and the H gene
Se gene (SeSe or Sese)
H antigen in secretions
A antigen
B antigen
se gene (sese)
No antigens secreted in saliva or other
body fluids
and/or
ABO Group ABH Substances
Secretors (SeSe or Sese): A B H
A +++ 0 +
B 0 +++ +
O 0 0 +++
AB +++ +++ +
Non-secretors (sese):
A, B, O, and AB 0 0 0
Sese + h/h (no H antigen) no antigens in secretions
Type I and Type II Precursors There are two potential precursors substances for
ABH antigens Type I and Type II Both are comprised of identical sugars but the
linkage of the terminal sugars differs in the two types Type I precursor has a terminal galactose linked to a
subterminal N-acetylgluosamine in a 1-3 linkage These same sugars combine in a 1-4 linkage in type
II precursor ABH Ags on red cells are derived from Type II
chains whereas the ABH Ags in plasma are made from both types I & II precursors
Type II H
After fucose is added to Type II chains, the structure is termed Type II H
Four kinds of Type II H have been identified H1, H2 are simple straight chain glycolipids Whereas H3 & H4 have branched chains
ABO Subgroups
ABO subgroups differ in the amount of antigen present on the red blood cell membrane Subgroups have less antigen
Subgroups are the result of less effective enzymes.
They are not as efficient in converting H antigens to A or B antigens (fewer antigens are present on the RBC)
Subgroups of A are more common than subgroups of B
Subgroups of A
The 2 principle subgroups of A are: A1 and A2
Both react strongly with reagent anti-A To distinguish A1 from A2 red cells, the lectin
Dolichos biflorus is used (anti-A1) 80% of group A or AB individuals are subgroup A1
20% are A2 and A2B
A2 Phenotype
Why is the A2 phenotype important? A2 and A2B individuals may produce an anti-A1
This may cause discrepancies when a crossmatch is done (incompatibility)
What’s the difference between the A1 and A2 antigen? It’s quantitative The A2 gene doesn’t convert the H3 & H4 to A very well The result is fewer A2 antigen sites compared to the many
A1 antigen sites
A1 and A2 Subgroups
Anti-A antisera
Anti-A1 antisera
Anti-H lectin
ABO antibodies in serum
# of antigen sites per
RBC
A14+ 4+ 0 Anti-B 900 x103
A24+ 0 3+ Anti-B &
anti-A1
250 x103
Other A subgroups There are other additional subgroups of A
Aint (intermediate), A3, Ax, Am, Aend, Ael, Abantu
A3 red cells cause mixed field agglutination when polyclonal anti-A or anti-A,B is used
Mixed field agglutination appears as small agglutinates with a background of unagglutinated RBCs
They may contain anti-A1
B Subgroups
B subgroups occur less than A subgroups B subgroups are differentiated by the type of
reaction with anti-B, anti-A,B, and anti-H B3, Bx, Bm, and Bel
Other ABO conditions
Bombay Phenotype (Oh) Inheritance of hh The h gene is an amorph and results in
little or no production of L-fucosyltransferase
Originally found in Bombay (now Mumbai) Very rare
Bombay The hh causes NO H antigen to be produced Results in RBCs with no H, A, or B antigen
(patient types as O) Bombay RBCs are NOT agglutinated with
anti-A, anti-B, or anti-H (no antigens present) Bombay serum has strong anti-A, anti-B and
anti-H, agglutinating ALL ABO blood groups What blood ABO blood group would you use
to transfuse this patient??
ANSWER:
Another Bombay Group O RBCs cannot be given because they still
have the H antigen You have to transfuse the patient with blood that
contains NO H antigen
ABO Blood Group
ABO Antibodies
Landsteiner’s Rule:
Normal, Healthy individuals possess ABO antibodies to the ABO antigen absent from their RBCs
ABO Blood Group System
The ABO Blood Group System was the first to be identified and is the most significant for transfusion practice
It is the ONLY system that the reciprocal antibodies are consistently and predictably present in the sera of people who have had no exposure to human red cells
Blood Group Systems
Most blood group systems (ABO and others) are made up of: An antigen on a red cell and the absence of it’s
corresponding antibody in the serum (if you’re A, you don’t have anti-A)
If you do NOT have a particular antigen on your red cells then it is possible (when exposed to foreign RBCs) to illicit an immune response that results in the production of the antibody specific for the missing antigen
ABO Remember:
The ABO Blood Group System does NOT require the presence of a foreign red blood cell for the production of ABO antibodies
ABO antibodies are “non-red blood cell stimulated” probably from environmental exposure and are referred to as “expected antibodies”
Titer of ABO Abs is often reduced in elderly and in patients with hypogammaglobulinemia
Infants do not produce Abs until 3-6 months of age
ABO antibodies
RBC Phenotype
Frequency (%)
Serum Ab
A 43 Anti-B
B 9 Anti-A
AB 4 --------
O 44 Anti-A,B
Anti-A1
Group O and B individuals contain anti-A in their serum
However, the anti-A can be separated into different components: anti-A and anti-A1
Anti-A1 only agglutinates the A1 antigen, not the A2 antigen
There is no anti-A2.
Anti-A1
Clinically SignificantSometimes
Abs classIgM
Thermal range4 - 22
HDNBNo
Transfusion Reactions
Extravascular Intravascular
No Rare
Anti-A,B
Found in the serum of group O individuals Reacts with A, B, and AB cells Predominately IgG, with small portions being
IgM Anti-A,B is one antibody, it is not a mixture of
anti-A and anti-B antibodies
ABO antibodies
IgM is the predominant antibody in Group A and Group B individuals Anti-A Anti-B
IgG (with some IgM) is the predominant antibody in Group O individuals Anti-A,B (with some anti-A and anti-B)
ABO antibody facts Complement can be activated with ABO antibodies
(mostly IgM, some IgG) High titer: react strongly (4+)
Anti-A, Anti-B, Anti-A,B
Clinically SignificantYes
Abs classIgM, less IgG
Thermal range4 - 37
HDNBYes
Transfusion Reactions
Extravascular Intravascular
Yes Yes
ABO Antibodies
Usually present within the first 3-6 months of life
Stable by ages 5-6 years Decline in older age & in
hypogammaglobulinemia Newborns may passively acquire maternal
antibodies (IgG crosses placenta)
Nature of antibodies
Non-red blood cell stimulated ABO antibodies
Red blood cell stimulated Antibodies formed as a result of transfusion, etc Usually IgG Active at 37°C Can occur in group O (may occur in group A or B) These antibodies also occur in the other Blood Group
Systems
Anti-H
Auto-Anti-H
Clinically Significant
No
Abs classIgM
Thermal range4 - 15
HDNBNo
Transfusion Reactions
Extravascular Intravascular
No No
Allo-Anti-H
Clinically Significant
Yes
Abs classIgM, IgG
Thermal range4 - 37
HDNBYes
Transfusion Reactions
Extravascular Intravascular
Yes Yes
RH System
M. Zaharna Blood Bank 2009
The Rh(D) Antigen
Rh is the most complex system, with over 45 antigens
The complexity of the Rh blood group Ags is due to the highly polymorphic genes that encode them.
Discovered in 1940 after work on Rhesus monkeys
The 2nd most important after ABO in the crossmatch test
Only the most clinically significant Ags will be discussed
Rh Genetics
The genes that control the system are autosomal codominant located on the short arm of chromosome 1.
M. Zaharna Blood Bank 2009
Rh blood group antigens are proteins
The antigens of the Rh blood group are proteins. The RhD gene encodes the D antigen, which is
a large protein on the red blood cell membrane, & the most important.
RHD gene RHCE gene
Chromosome 1
Proteins
M. Zaharna Blood Bank 2009
Rh Antigen Frequency
D antigen – 85% d antigen – 15% C antigen – 70% c antigen – 80% E antigen – 30% e antigen – 98%
The presence or absence of D Ag determines if the person is Rh+ or Rh-
Rh PositiveRh Positive
Rh NegativeRh Negative
M. Zaharna Blood Bank 2009
Weak D Phenotype Most D positive rbc’s react macroscopically with
Reagent anti-D at immediate spin These patients are referred to as Rh positive Reacting from 1+ to 3+ or greater
HOWEVER, some D-positive rbc’s DO NOT react (do NOT agglutinate) at Immediate Spin using Reagent Anti-D. These require further testing (37oC and/or AHG) to determine the D status of the patient.
M. Zaharna Blood Bank 2009
Rh Deleted
Red cells that express no Ags at the C & E loci ( D )
Number of D Ags greatly increase Anti-D IgG Abs can agglutinate these cells
M. Zaharna Blood Bank 2009
RH null: individual that appears to have no Rh antigens ( , , )
RBC has fragile membrane- short lived Must use autologous blood products
No D, C, c, E, e antigens present on the RBC membrane Demonstrate mild hemolytic anemia (Rh antigens are
integral part of RBC membrane and absence results in loss of membrane integrity) Stomatocytosis.
When transfusion is necessary ONLY Rh Null blood can be used to transfuse.
Rh null
M. Zaharna Blood Bank 2009
Rh antibodies
Result from the exposure to Rh antigens
IgG form Bind at 37°C Form agglutination in
IAT phase
Rh AbsClinically
SignificantYes
Abs classIgG
Thermal range4 - 37
HDNBYes
Transfusion Reactions
Extravascular Intravascular
Yes No
M. Zaharna Blood Bank 2009
Related to Hemolytic transfusion reactions Re-exposure to antigen cause rapid
secondary response Always check patients history for previous
transfusion or pregnancy to avoid re-exposure.
Clinical Significance of Rh antibodies
M. Zaharna Blood Bank 2009
Usually related to D antigen exposure and the formation of anti-D
Usually results from D negative female and D positive male producing and offspring. The baby will probably be D positive.
1st pregnancy not effected, the 2nd pregnancy and on will be effected-results in still birth, severe jaundice, anemia related to HDN.
To prevent this occurrence the female is administered RHIG.
Hemolytic disease of the Newborn (HDN)
M. Zaharna Blood Bank 2009
• Rh factor can cause complications in some pregnancies.
• Mother is exposed to Rh antigens at the birth of her Rh+ baby.
First pregnancy
PlacentaRh+ antigens
Rh factor
M. Zaharna Blood Bank 2009
Anti-Rh+ antibodies
Possible subsequent pregnancies
• Mother makes anti-Rh+ antibodies.
• During the mother’s next pregnancy, Rh antibodies can cross the placenta and endanger the fetus.
M. Zaharna Blood Bank 2009
Significance
After ABO, the Rh system is the second most important system. This is because:
The D antigen is extremely immunogenic. It causes the production of anti-D in 50 - 70% of Rh(D)
negative people who are exposed to the D antigen. Moreover, anti-D is the most common cause of severe
HDN and can cause in Utero death. Because of this, in blood transfusion, the patient and
donor are matched for Rh(D) type as well as ABO groups.
The C and E Ags are not as immunogenic as D, routine typing for these Ags is not performed