ABO Incompatibility

Group 9

Saliba • Samonte • Samoy

Segubre • Sese • Solana

Sta. Ana • Tan Gana • Tee

Definition of Terms

• Antigen: Any substance that when introduced in to, or present in, the tissues or blood causes the formation of antibodies and only reacts with its specific antibodies

• Antibody: A protein produced by certain cells of the body in the presence of a specific antigen. The antibody combines with that antigen to inhibit, neutralize or destroy it

• Agglutinogen: An antigen located on the surface plasma membrane of RBC which determines the blood group of the individual.

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Definition of Terms

• Agglutinin: A specific antibody in blood plasma capable of causing the clumping of RBC or bacteria or particles such as viruses

• Agglutination: The clumping together of blood cells or microorganisms, usually due to an antigen-antibody reaction

• Blood group: The type or specification of an individual’s bloo according to the presence or absence of specific agglutinogens on the red cells

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Definition of Terms

Blood transfusion: The introductioof blood from one person into the circulation of another person

• Incompatibility: When the agglutinogens on the red cells in the donor react with the agglutinins in the recipient’s blood.

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DISCOVERY OFABO

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Karl Landsteiner(1868-1943)

A, B, O

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• 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.

• Sturle and Von Descatello - AB

Functions of The Red Blood Cell

• Delivers oxygen to the tissues

• Helps in the disposal of carbon dioxide and protons formed by tissue metabolism.

• life span -120 days

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BLOOD GROUP SYSTEM

discovered by the Austrian scientist Karl Landsteiner, who found three different blood types in year 1900

ABO blood group system is the most important blood type system (or blood group system) in human blood transfusion

defined by two red blood cell antigens, A and B, whose presence or absence is determined by three alleles (A, B, O) segregating at a single genetic locus

• An unusual feature of this system is the presence of serum IgM antibodies in healthy adults

which are usually produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses

• to whichever antigen (A or B) is absent from that individual's cells

Two basic rules:

The blood "type" is defined by the presence of two red blood cell antigens, "A" and "B." RBCs of type A have the A antigen on their surface, those of type B have antigen B, type AB red cells bear both antigens, while type O cells bear neither antigen.

"Natural" antibodies called isoagglutinins exist in an individual's serum, directed against whichever of the A and B antigens is not present on that person's red cells.

Definition of Terms

• Glucosyltransferase – enzyme that facilitates the transfer of carbohydrate molecules onto carbohydrate precursor molecules

• Immunodominant Sugar – sugar molecule that completes the antigenic determinant when combined with the precursor substance

• Amorph – a mutant allele that has little or no effect on the expression of trait

• Allele – any alternate form of a gene that can occupy a given chromosomal location (locus)

• Isoagglutins – defined as antibodies that agglutinate blood cells of some individuals of the same species

• Agglutinogen - An antigen that stimulates the production of a particular agglutinin, such as an antibody. (Agglutogen)

• Agglutinin - antibody which aggregates a particulate antigen, e.g., bacteria, red blood cells, following combination with the homologous antigen

ABO BLOOD GROUP

• Based on two agglutinogens referred to as A and B.• Individuals whose erythrocytes develop only Antigen A

are said to have blood type A.

• Those whose erythrocytes develop only agglutinogen B are said to have blood group B.

• Some individuals, who have erythrocytes which develop both agglutinogen A and B, are said to have blood group AB.

• Those individuals who manufacture neither agglutinogen are said to have blood group O.

• The blood group agglutinins, a and b, are present in the plasma of the individuals

• Blood group A plasma contains agglutinin b

• Blood group B plasma contains agglutinin a

• Blood group AB contains neither of the agglutinin

• Blood group O contains both agglutinin a and b

ABH Antigens

• The inheritance of ABO blood group demonstrates that each individual inherits ABO gene from each parent and these two genes will determine the antigen present on RBC membrane

• One position or locus on each chromosome 9 is occupied with A, B, or O gene.

• A locus termed H and the final product of the genes at the locus is H antigen. It is necessary for the expression of normal ABO antigens.

H Antigen

• The biosynthesis of the H antigen and the A and B antigens involves a series of enzymes (glycosyltransferases) that transfer monosaccharides. The resulting antigens are oligosaccharide chains, which are attached to lipids and proteins that are anchored in the RBC membrane.

• The H antigen is produced by a specific fucosyltransferase. Depending upon a person's ABO blood type, the H antigen is converted into either the A antigen, B antigen, or both. If a person has blood group O, the H antigen remains unmodified. Therefore, the H antigen is present in the highest amounts in blood type O and in the least amounts in blood type AB.

• Individuals who are homozygous for null alleles at this locus (h/h) do not produce H antigen, and because the H antigen is an essential precursor to the ABO blood group antigens, they cannot produce A and B antigens. Therefore, their serum contains anti-A and anti-B, in addition to potent anti-H. This rare phenotype of H-deficient RBCs is called the "Bombay phenotype" (Oh)

• Individuals with the Bombay phenotype are healthy, but if they ever needed a blood transfusion, the antibodies in their serum would place them at a high risk of having an acute hemolytic transfusion reaction. This can be avoided by using only blood products from a donor who also has the Bombay phenotype (usually a relative).

RBC Antigens

• Blood group antigens are either sugars or proteins.

• the antigens of the Rh blood group are proteins

• the antigens of the ABO blood group are sugars, specifically oligosaccharides

Glycosyltransferases

• Oligosaccharides are synthesized through the action of specific enzymes: glycosyltransferases

• oligosaccharide foundation called the O (or sometimes H) antigen

• A and B antigens differ from the O antigen by the addition of one extra monosaccharide, either N-acetylgalactosamine (for A) or galactose (for B) through an α-1,3 linkage to the galactose terminal

A / B / O diagrams

N-Acetylgalactosamine

• N-acetyl galactosamine transferase. • An A blood group individual possess this enzyme

• Transfers N-acetyl galactosamine to the terminal sugar on the H Substance forming A antigen

• IUPAC Name:• 2-(Acetylamino)-2-deoxy-D-galactose

Galactose

• D-galactose transferase. • The B blood group individual possesses this enzyme

• Transfers the sugar D-galactose to the terminal sugar on the H substance forming B antigen

AB Type

• Consist of two different terminal sugars, N-acetyl galactosamine and D-galactose, are transferred to different chains of the same RBC.

• A and B antigens are formed only when terminal sugar L-fucose is added to the precursor substance.

• In the absence of the H antigen, there is no production of A or B antigen.

Antigen Genetics

• The ABO locus encodes specific glycosyltransferases that synthesize A and B antigens on RBCs.

• For A/B antigen synthesis to occur, a precursor called the H antigen must be present.

• In RBCs, the enzyme that synthesizes the H antigen is encoded by the H locus (FUT1).

• In saliva and other bodily secretions, the enzyme that synthesizes the H antigen is encoded by the Se locus (FUT2).

Antigen Genetics

• The H locus is located on chromosome 19 at 19q13.3. • it encodes a fucosyltransferase that produces the H antigen on RBCs. • Individuals who are homozygous for null alleles at this locus (h/h)

do not produce H antigen, and because the H antigen is an essential precursor to the ABO blood group antigens, they cannot produce A and B antigens.

• Therefore, their serum contains anti-A and anti-B, in addition to potent anti-H. This rare phenotype of H-deficient RBCs is called the "Bombay phenotype"

• Individuals with the Bombay phenotype are healthy, but if they ever needed a blood transfusion, the antibodies in their serum would place them at a high risk of having an acute hemolytic transfusion reaction.

• This can be avoided by using only blood products from a donor who also has the Bombay phenotype (usually a relative).

Antigen Genetics

• The ABO locus is located on chromosome 9 at 9q34.1-q34.2.

• The A and B alleles differ from each other by seven nucleotide substitutions, four of which translate into different amino acids in the gene product (R176G, G235S, L266M, G268A).

• The residues at positions 266 and 268 determine the A or B specificity of the glycosyltransferase they encode.

• The O allele differs from the A allele by deletion of guanine at position 261.

• The deletion causes a frameshift and results in translation of an almost entirely different protein that lacks enzymatic activity.

Agglutination

• Occurs when an antibody interacts with antigen, resulting in cross-linking of the antigen particles by the antibody. This eventually leads to clumping.

• May occur when an undeterminate, multivalent antigen interacts with a single antibody. It may also occur if a multi determinate, univalent antigen interacts with at least two distinct antibodies.

• Blood typing is one common application for the agglutination test. There are different blood groups like A,B, AB and O.

• Agglutination occurs if the antibodies match the epitopes of the blood cells.

• Observing the agglutination patterns, the blood type of the individual can be determined.

ABO Typing

• method to determine an individual’s specific blood type

• blood types are differentiated according to the types of proteins or antigens on the surfaces of the red blood cells

• shows that people have one of four blood types: A, B, AB, or O

• Type A: has A antigen in the RBCs and type B antibodies in the plasma

• Type B: has B antigen in the RBCs and type A blood antibodies in the plasma

• Type O: neither has the A nor B antigen but has both type A and type B antibodies

• Type AB: has both the A and B antigens but does not have antibodies against type A or type B blood

How the test is performed

• Antigen typing and antibody detection

• Antigen typing – forward typing

• Antibody detection – reverse, back typing, or serum confirmation

Forward typing

• determines antigens on the donor's cells 

a. Cells are tested with the antisera reagents anti-A and anti-B

Reverse typing

• determines antibodies in patient's or donor's serum or plasma 

a. Serum tested with reagent A cells and B cells 

Expected results

Routine ABO Typing

Reaction of Cells Tested With

Red Cell ABO Group

Reaction of Serum Tested Against

Reverse ABO Group

Anti-A Anti-B   A1 Cells B Cells  

0 0 O + + O

+ 0 A 0 + A

0 + B + 0 B

+ + AB 0 0 AB

Blood Transfusion

• The process of transferring whole blood or blood components from one person (donor) to another (recipient).

• Blood can be provided from two sources: Autologous or Donor blood.

RBC Compatibility

Blood Transfusion Reactions

• Transfusion reactions require immediate recognition, laboratory investigation, and clinical management.

• If a transfusion reaction is suspected during blood administration, the safest practice is to stop the transfusion and keep the intravenous line open with 0.9% sodium chloride (normal saline).

Classification

• Acute (Immediate) reactions : Symptoms appear within minutes or up to 24 hrs post transfusion.

• Delayed reactions : Reactions occurring more than 24 hours following transfusion. (Up to months following)

Immediate Adverse Effects & Their Management

Immediate Adverse Effects & Their Management

Immediate Adverse Effects & Their Management