3. ABO Grouping

7/28/2019 3. ABO Grouping

1/59

29-Jun-13 1

BLOOD GROUPS

Presented by:

Dr.Agus Alim Abdullah,SpPK(K)Clinical Pathologist Hematology Consultant

7/28/2019 3. ABO Grouping

2/59

29-Jun-13 2

*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

antigens that are regulated either by allelicgenes or closely linked genes.

7/28/2019 3. ABO Grouping

3/59

29-Jun-13 3

7/28/2019 3. ABO Grouping

4/59

*

A blood type (also called a blood group) is

a classification ofblood based on the

presence or absence ofinheritedantigenicsubstances on the surface ofred blood cells

(RBCs). These antigens may beproteins,

carbohydrates, glycoproteins, orglycolipids, depending on the blood group

system.

29-Jun-13 4

7/28/2019 3. ABO Grouping

5/59

*

Some of these antigens are also present on the

surface of other types ofcells of various tissues.

Several of these red blood cell surface antigensthat stem from one allele (or very closely linked

genes), collectively form a blood group system.[1]

Blood types are inherited and represent

contributions from both parents. A total of 30human blood group systems are now recognized

by the International Society of Blood Transfusion

(ISBT)

29-Jun-13 5

7/28/2019 3. ABO Grouping

6/59

*

Manypregnant women carry a fetus with a

different blood type from their own, and the

mother can form antibodies against fetal RBCs.Sometimes these maternal antibodies are IgG, a

small immunoglobulin, which can cross the

placenta and cause hemolysis of fetal RBCs,

which in turn can lead to hemolytic disease of thenewborn, an illness oflow fetal blood counts that

ranges from mild to severe

29-Jun-13 6

7/28/2019 3. ABO Grouping

7/59

29-Jun-13 7

The number or red cell blood groups now exceeds 400 (tab 1).

Table 1. Survey of major Red Cell Blood Group System

System Important antigens

ABO 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 Dia,Dib

Cartwright Yta,Ytb

Xg Xga

Dombrock Doa,Dob

Colton Coa,Cob

7/28/2019 3. ABO Grouping

8/59

Blood group systems

A complete blood type would describe a full

set of 30 substances on the surface of RBCs,

and an individual's blood type is one of themany possible combinations of blood-group

antigens.[2] Across the 30 blood groups,

over 600 different blood-group antigenshave been found,[4] but many of these are

very rare or are mainly found in certain

ethnic groups29-Jun-13 8

7/28/2019 3. ABO Grouping

9/59

Almost always, an individual has the same blood group for life, but

very rarely an individual's blood type changes through addition or

suppression of an antigen in infection, malignancy, orautoimmune

disease.

[5][6][7][8]

An example of this rare phenomenon is the case ofDemi-Lee Brennan, an Australian citizen, whose blood group changed

after a livertransplant.[9][10] Another more common cause in blood-

type change is abone marrow transplant. Bone-marrow transplants are

performed for many leukemias and lymphomas, among other diseases.

If a person receives bone marrow from someone who is a different

ABO type (e.g., a type A patient receives a type O bone marrow), the

patient's blood type will eventually convert to the donor's type

29-Jun-13 9

7/28/2019 3. ABO Grouping

10/59

7/28/2019 3. ABO Grouping

11/59

The ABO system

is the most important blood-group system in

human-blood transfusion. The associated anti-A

antibodies and anti-B antibodies are usuallyImmunoglobulin M, abbreviated IgM, antibodies.

ABO IgM antibodies are produced in the first

years of life by sensitization to environmental

substances such as food,bacteria, and viruses. TheO in ABO is often called 0 (zero, ornull) in other

languages

29-Jun-13 11

7/28/2019 3. ABO Grouping

12/59

Phenotype Genotype

A AA or AO

B BB or BO

AB AB

O OO

29-Jun-13 12

7/28/2019 3. ABO Grouping

13/59

Rh blood group system

The Rh system is the second most significant

blood-group system in human-blood transfusion

with currently 50 antigens. The most significantRh antigen is the D antigen because it is the most

likely to provoke an immune system response of

the five main Rh antigens. It is common for D-

negative individuals not to have any anti-D IgG orIgM antibodies, because anti-D antibodies are not

usually produced by sensitization against

environmental substances

29-Jun-13 13

7/28/2019 3. ABO Grouping

14/59

However, D-negative individuals can produce IgG anti-D

antibodies following a sensitizing event: possibly a

fetomaternal transfusion of blood from a fetus in

pregnancy or occasionally a blood transfusion with Dpositive RBCs.[15]Rh disease can develop in these

cases.[16] Rh negative blood types are much less in

proportion of Asian populations (0.3%) than they are in

White (15%).[17]

In the table below, the presence orabsence of the Rh antigens is signified by the + or - sign,

so that for example A- group does not have any of the Rh

antigens

29-Jun-13 14

7/28/2019 3. ABO Grouping

15/59

Red blood cell compatibility

Recipient Donor

29-Jun-13 15

O O+ A A+ B B+ AB AB+

O Y

O+ Y Y

A Y Y

A+ Y Y Y Y

B Y Y

B+ Y Y Y Y

AB Y Y Y Y

AB+ Y Y Y Y Y Y Y Y

7/28/2019 3. ABO Grouping

16/59

An Rh D-negative patient who does not

have any anti-D antibodies (never being

previously sensitized to D-positive RBCs)can receive a transfusion of D-positive

blood once, but this would cause

sensitization to the D antigen, and a femalepatient would become at risk forhemolytic

disease of the newborn

29-Jun-13 16

7/28/2019 3. ABO Grouping

17/59

If a D-negative patient has developed anti-D antibodies, a

subsequent exposure to D-positive blood would lead to a

potentially dangerous transfusion reaction. Rh D-positive

blood should never be given to D-negative women of childbearing age or to patients with D antibodies, so blood

banks must conserve Rh-negative blood for these patients.

In extreme circumstances, such as for a major bleed when

stocks of D-negative blood units are very low at the bloodbank, D-positive blood might be given to D-negative

females above child-bearing age or to Rh-negative males,

providing that they did not have anti-D antibodies, to

conserve D-negative blood stock in the blood bank29-Jun-13 17

7/28/2019 3. ABO Grouping

18/59

The converse is not true; Rh D-positive

patients do not react to D negative blood.

This same matching is done for otherantigens of the Rh system as C, c, E and e

and for other blood group systems with a

known risk for immunization such as theKell system in particular for females of

child-bearing age or patients with known

need for many transfusions.29-Jun-13 18

7/28/2019 3. ABO Grouping

19/59

29-Jun-13 19

Plasma compatibility

7/28/2019 3. ABO Grouping

20/59

Plasma compatibility table

Recipient Donor

29-Jun-13 20

O A B AB

O Y Y Y Y

A Y Y

B Y Y

AB Y

7/28/2019 3. ABO Grouping

21/59

Rh D antibodies are uncommon, so generally neither D

negative nor D positive blood contain anti-D antibodies. If

a potential donor is found to have anti-D antibodies or any

strong atypical blood group antibody by antibody

screening in the blood bank, they would not be accepted as

a donor (or in some blood banks the blood would be drawn

but the product would need to be appropriately labeled);

therefore, donor blood plasma issued by a blood bank can

be selected to be free of D antibodies and free of otheratypical antibodies, and such donor plasma issued from a

blood bank would be suitable for a recipient who may be D

positive or D negative, as long as blood plasma and the

recipient are ABO compatible29-Jun-13 21

7/28/2019 3. ABO Grouping

22/59

Universal donors and universal recipients

With regard to transfusions of whole blood or packed red

blood cells, individuals with type O Rh D negative blood

are often called universal donors, and those with type AB

Rh D positive blood are called universal recipients;however, these terms are only generally true with respect

to possible reactions of the recipient's anti-A and anti-B

antibodies to transfused red blood cells, and also possible

sensitization to Rh D antigens. One exception isindividuals with hh antigen system (also known as the

Bombay blood group) who can only receive blood safely

from other hh donors, because they form antibodies against

the H substance29-Jun-13 22

7/28/2019 3. ABO Grouping

23/59

Blood donors with particularly strong anti-

A, anti-B or any atypical blood group

antibody are excluded from blood donation.The possible reactions of anti-A and anti-B

antibodies present in the transfused blood to

the recipients RBCs need not be considered,because a relatively small volume of plasma

containing antibodies is transfused

29-Jun-13 23

7/28/2019 3. ABO Grouping

24/59

By way of example: considering the transfusion of O Rh D

negative blood (universal donor blood) into a recipient of

blood group A Rh D positive, an immune reaction between

the recipient's anti-B antibodies and the transfused RBCs isnot anticipated. However, the relatively small amount of

plasma in the transfused blood contains anti-A antibodies,

which could react with the A antigens on the surface of the

recipients RBCs, but a significant reaction is unlikelybecause of the dilution factors. Rh D sensitization is not

anticipated.

29-Jun-13 24

7/28/2019 3. ABO Grouping

25/59

Additionally, red blood cell surface antigens other

than A, B and Rh D, might cause adverse

reactions and sensitization, if they can bind to thecorresponding antibodies to generate an immune

response. Transfusions are further complicated

becauseplatelets and white blood cells (WBCs)

have their own systems of surface antigens, andsensitization to platelet or WBC antigens can

occur as a result of transfusion

29-Jun-13 25

7/28/2019 3. ABO Grouping

26/59

With regard to transfusions ofplasma, this

situation is reversed. Type O plasma, containing

both anti-A and anti-B antibodies, can only begiven to O recipients. The antibodies will attack

the antigens on any other blood type. Conversely,

AB plasma can be given to patients of any ABO

blood group due to not containing any anti-A oranti-B antibodies

29-Jun-13 26

7/28/2019 3. ABO Grouping

27/59

29-Jun-13 27

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

7/28/2019 3. ABO Grouping

28/59

29-Jun-13 28

Isohemagglutinins with ABO are always

clinically significant

Isohemagglutinins elicited by similar

sequences on microbial surfaces >>Ig Ms

effective hemolysis because they efficiently

fix complement.

Occasionally Ig G a.bodies specific for thesea.g also appear.

7/28/2019 3. ABO Grouping

29/59

29-Jun-13 29

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.

7/28/2019 3. ABO Grouping

30/59

29-Jun-13 30

3. Immunized humans

The third major source of the blood group anti

bodies are donors who have been allogenically

immunized either by (1) prior blood

transfusions or (2) previous pregnancies

immune antibodies elicited by prior

exposure to red cell a.g are commonly IgGs

7/28/2019 3. ABO Grouping

31/59

29-Jun-13 31

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).

7/28/2019 3. ABO Grouping

32/59

29-Jun-13 32

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

7/28/2019 3. ABO Grouping

33/59

29-Jun-13 33

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

7/28/2019 3. ABO Grouping

34/59

29-Jun-13 34

Table 2. Chromosome Assignment of Some Blood

Group Loci

Locus Chromosome

ABO 9

Rh 1Fy 1

Chido, Rogers 6

MNSs 4Xg X

Sc 1

7/28/2019 3. ABO Grouping

35/59

29-Jun-13 35

ABO SYSTEM

a. Historical notesIn subsequent work Landsteiner recognized

that the pattern of reactions could be

explained by two a.g, which designated Aand B. O signified the state of not having A

or B.

Table 3. The Landsteiner scheme

7/28/2019 3. ABO Grouping

36/59

29-Jun-13 36

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

7/28/2019 3. ABO Grouping

37/59

29-Jun-13 37

b. Subdivisions of A antigen

A antigen and anti-A are complex. Anti-A

serum 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

+

+

+

-

7/28/2019 3. ABO Grouping

38/59

29-Jun-13 38

Genetics

Determining the blood group : genotype and

phenotype. A child receives one of four genes

from each parent : A1, A2, B, 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, A1 O, A1A2). Group A2can have either A2A2 or A2 O genotypes. Group

B can have either BB or BO genotypes

7/28/2019 3. ABO Grouping

39/59

29-Jun-13 39

Genotype :

- specific genes that person carries

- determined by family studies

- AA, AO, BB, BO, AB and OO

- see fig 1.

Family 1

7/28/2019 3. ABO Grouping

40/59

29-Jun-13 40

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

7/28/2019 3. ABO Grouping

41/59

29-Jun-13 41

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)

7/28/2019 3. ABO Grouping

42/59

29-Jun-13 42

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

7/28/2019 3. ABO Grouping

43/59

29-Jun-13 43

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

7/28/2019 3. ABO Grouping

44/59

29-Jun-13 44

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 doesnttransform the H substance

7/28/2019 3. ABO Grouping

45/59

29-Jun-13 45

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

7/28/2019 3. ABO Grouping

46/59

29-Jun-13 46

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

7/28/2019 3. ABO Grouping

47/59

29-Jun-13 47

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

7/28/2019 3. ABO Grouping

48/59

29-Jun-13 48

Rhesus System

7/28/2019 3. ABO Grouping

49/59

29-Jun-13 49

Rhesus a.b >> immune (previous

transfusion or pregnancy), naturally

7/28/2019 3. ABO Grouping

50/59

29-Jun-13 50

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)

7/28/2019 3. ABO Grouping

51/59

29-Jun-13 51

2. Weiner system

3. Rosenfield system

B. Compound antigens

C. Weakened antigens :

- weakly reactive ag

D

u

- formal terminology : Rh +, Du variant

- for transfusion : Du is equivalent toRh +

D. Deleted antigens : Rh null cells.E. Rh antigens structure

T bl 6 Rh l

7/28/2019 3. ABO Grouping

52/59

29-Jun-13 52

Table 6. Rh gene complexes

Fischer-Race Wiener

CDe R1

cde r

cDE R2

cDe Ro

CwDe R1W

cdE ru

Cde r1

CDE Rz

Other clinicall significant s stems

7/28/2019 3. ABO Grouping

53/59

29-Jun-13 53

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.

3 Kidd t

7/28/2019 3. ABO Grouping

54/59

29-Jun-13 54

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.

5 X a bl d

7/28/2019 3. ABO Grouping

55/59

29-Jun-13 55

5. Xga blood group

This a.g is controlled by a gene on the X

chromosome. Its not clinically significant but

is of interest as a marker for X chromosome

that appear to escape inactivation by the

Lyon mechanism.

The ABO and Rhesus (Rh) groups are of major clinical

7/28/2019 3. ABO Grouping

56/59

29-Jun-13 56

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

7/28/2019 3. ABO Grouping

57/59

29-Jun-13 57

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

7/28/2019 3. ABO Grouping

58/59

29-Jun-13 58

B. In geneticschromosome mapping

C. In forensic medicine :

1. Identification studies

2. Paternity testing

7/28/2019 3. ABO Grouping

59/59

Thank you