BLOOD GROUPS

Dr.Agus Alim Abdullah,SpPK(K)

Clinical Pathologist Hematology Consultant

Presented by:

29-Jun-13

*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 allelic genes or closely linked genes.
29-Jun-13 2

29-Jun-13

*
A blood type (also called a blood group) is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system.
29-Jun-13 4

*
Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens that 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 30 human blood group systems are now recognized by the International Society of Blood Transfusion (ISBT)
29-Jun-13 5

*
Many pregnant 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 the newborn, an illness of low fetal blood counts that ranges from mild to severe
29-Jun-13 6

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 MNSs P Rh Lutheran Kell Lewis Wright Diego Cartwright Xg Dombrock Colton A1,A2,B,H,A3,Am,Ax M,N,S,s,U,Mg,Mia,Hu,HeMta,Vw,M2,N2,S2 P1,pk,P2,(Tja) D,C,E,c,e,Cw,Ew,ce,Ce,G,CE,cE,Du,Cu,Eu,LW Lua,Lub K,k,Kpa,Kpb,Jsa,Jsb Lea,Leb Wra,Wrb Dia,Dib Yta,Ytb Xga Doa,Dob Coa,Cob

29-Jun-13

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 the many possible combinations of blood-group antigens.[2] Across the 30 blood groups, over 600 different blood-group antigens have been found,[4] but many of these are very rare or are mainly found in certain ethnic groups
29-Jun-13 8

 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, or autoimmune disease.[5][6][7][8] An example of this rare phenomenon is the case of Demi-Lee Brennan, an Australian citizen, whose blood group changed after a liver transplant.[9][10] Another more common cause in bloodtype change is a bone 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

 Some blood types are associated with inheritance of other diseases; for example, the Kell antigen is sometimes associated with McLeod syndrome.[11] Certain blood types may affect susceptibility to infections, an example being the resistance to specific malaria species seen in individuals lacking the Duffy antigen.[12] The Duffy antigen, presumably as a result of natural selection, is less common in ethnic groups from areas with a high incidence of malaria
29-Jun-13 10

The ABO system

is the most important blood-group system in human-blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually Immunoglobulin 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. The O in ABO is often called 0 (zero, or null) in other languages
29-Jun-13 11

Phenotype A B AB O
29-Jun-13

Genotype AA or AO BB or BO AB OO
12

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 significant Rh 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 Dnegative individuals not to have any anti-D IgG or IgM antibodies, because anti-D antibodies are not usually produced by sensitization against environmental substances
29-Jun-13 13

 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 D positive 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 or absence 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

Red blood cell compatibility

Recipient O O+ O Y O+ Y Y A Y A+ Y Y B Y B+ Y Y AB Y AB+ Y Y A A+ Donor B B+ AB AB+

Y Y

Y Y

Y Y Y Y

Y Y Y Y Y

29-Jun-13

15

 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 female patient would become at risk for hemolytic disease of the newborn
29-Jun-13 16

 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 child bearing 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 blood bank, 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 bank
29-Jun-13 17

 The converse is not true; Rh D-positive patients do not react to D negative blood. This same matching is done for other antigens of the Rh system as C, c, E and e and for other blood group systems with a known risk for immunization such as the Kell system in particular for females of child-bearing age or patients with known need for many transfusions.
29-Jun-13 18

Plasma compatibility

29-Jun-13

19

Plasma compatibility table

Recipient Donor

O
O A B AB
29-Jun-13

A
Y Y

B
Y

AB
Y Y

Y Y
20

 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 other atypical 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 compatible
29-Jun-13

21

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 is individuals 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 substance
29-Jun-13 22

 Blood donors with particularly strong antiA, 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

 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 is not 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 unlikely because of the dilution factors. Rh D sensitization is not
anticipated.
29-Jun-13 24

 Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response. Transfusions are further complicated because platelets and white blood cells (WBCs) have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion
29-Jun-13 25

 With regard to transfusions of plasma, this situation is reversed. Type O plasma, containing both anti-A and anti-B antibodies, can only be given 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 or anti-B antibodies

29-Jun-13

26

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
29-Jun-13 27

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 these a.g also appear.
29-Jun-13 28

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 carefully absorbed with human red cells to establish specificity. Recently developed a.g specific monoclonal a.bodies do not require such absorption.
29-Jun-13 29

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

29-Jun-13

30

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).
29-Jun-13 31

b. Insertion of a.b red cells bridges Agglutinations may produced or enhanced

by addition of Coomb reagent (i.e.,antiglobulin a.body)

3. Use of lectins
4. Automated techniques

29-Jun-13

32

Genetics
According to Mendelian laws Heredity is generally autosomal codominant i.e there is an expression of both alleles in the heterozygous individual 1. Linked genes 2. Interaction with other genes 3. Loci of blood groups genes on chromosomes (table 2) 4. Occurrence of blood group antigens
29-Jun-13 33

Table 2. Chromosome Assignment of Some Blood Group Loci Locus ABO Rh Fy Chido, Rogers MNSs Xg Sc
29-Jun-13

Chromosome 9 1 1 6 4 X 1
34

ABO SYSTEM
a. Historical notes In subsequent work Landsteiner recognized that the pattern of reactions could be explained by two a.g, which designated A and B. O signified the state of not having A or B.
Table 3. The Landsteiner scheme

29-Jun-13

35

Table 3. The ABO system defined by Anti-A and Anti B

Blood Groups O A B AB Antigens on RC None A B A and B Antibodies in serum Anti-A and Anti-B Anti-B Anti-A None

29-Jun-13

36

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

29-Jun-13

37

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 (A1 A1, A1 O, A1A2). Group A2 can have either A2A2 or A2 O genotypes. Group B can have either BB or BO genotypes
29-Jun-13 38

 Genotype : - specific genes that person carries

- determined by family studies

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

- see fig 1.

29-Jun-13

39

Family 1

Phenotype Genotype

B BO

A1 A1O

Phenotype Genotype

O OO

O OO

A1B A1B

Family 2

Phenotype Genotype

A1 A1A2

A2B A2B

Phenotype Genotype

A2B A2B

A1 A1A2

Fig 1. Illustration of usefulness of family studies in the elucidation of phenotype

29-Jun-13 40

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)

29-Jun-13

41

Table 5. Blood Type

Phenotype Genotype Antigens on red cell Antibodies in plasma

O A B AB

OO AA or AO BB or BO AB

O A B AB

Anti-A, Anti-B Anti-B Anti-A None

29-Jun-13

42

Fig.2 Synthesis of ABH antigens

R
glc gal glcnac Hh gen gal H precursor

fuc R glc gal glcnac gal H antigen

A gene

B gene

fuc R glc
29-Jun-13

fuc R glc gal glcnac gal B antigen gal

43

gal

glcnac gal A antigen

glcnac

H antigen
The surfaces oligosaccharides that

constitutes 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 doesnt transform the H substance
29-Jun-13 44

Rare variant Bombay, 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

29-Jun-13

45

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 Le gene
29-Jun-13 46

b. P system
These ag were recognized by antisera developed in rabbits glycosphingolipids and originate on a ceramide dihexose (GalGal-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
29-Jun-13 47

Rhesus System

29-Jun-13

48

Rhesus a.b >> immune (previous transfusion or pregnancy), naturally << Anti-D is responsible for most of the clinical problems associated with the system the simple subdivision of subjects into Rh D + and Rh D , using anti-D is sufficient for routine clinical purposes.

29-Jun-13

49

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 D antigen, also called Rh or Rh factor Rhesus negative absence of D but doesnt denote absence of other a.g of the Rh system (C,c,E or e)
29-Jun-13 50

B. C.

D. E.

2. Weiner system 3. Rosenfield system Compound antigens Weakened antigens : - weakly reactive ag Du - formal terminology : Rh +, Du variant - for transfusion : Du is equivalent to Rh + Deleted antigens : Rh null cells. Rh antigens structure
51

29-Jun-13

Table 6. Rh gene complexes

Fischer-Race CDe cde cDE cDe CwDe cdE Cde CDE Wiener R1 r R2 Ro R1W ru r1 Rz

29-Jun-13

52

Other clinically significant systems

1. Kell system The Kell a.g system rivals the Rh system in its complexity 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 Duffysensitive individuals can cause severe hemolysis.
29-Jun-13 53

3. Kidd system Immunization to Kidd is caused mainly by transfusions. Kidd a.b are evanescent warm-active incomplete 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 caused by either dominant inhibitor gene or a recessive silent allele.
29-Jun-13 54

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.

29-Jun-13

55

The ABO and Rhesus (Rh) groups are of major clinical significance. Some other systems of less overall importance are listed in table 7.
Systems ABO Rh Kell Duffy Kidd Lutheran Lewis P MN Ii
29-Jun-13

Frequency of a.body Very common Common Occasional Occasional Occasional Rare Occasional Occasional Rare Rare

Cause of HDN Yes Yes Yes Yes Yes No No Yes (rare) Yes (rare) No
56

Uses of blood grouping data

A. In clinical medicine

1. Pretransfusion testing :
Prior to transfusion, blood is typed

and crossmatched to establish ABO and

D compatibility

2. Hemolytic disease of the newborn

29-Jun-13

57

B. In genetics chromosome mapping

C. In forensic medicine :

1. Identification studies
2. Paternity testing

29-Jun-13

58

Thank you

29-Jun-13

59