Transfusion & Transplantation notes
Week 1 Lectorial Plan-ABO and Rh blood group systems.
Questions:
1. Who discovered the ABO blood group system? What were the observations made
that helped determine the ABO blood group system?
- Karl Landsteiner 1901. Won Nobel Prize for the discovery. Karl was working in Vienna
and he collected blood from colleagues and let the plasma and red blood cells separate by
gravity. He then mixed different plasmas with red blood cells and noticed different
patterns of agglutination. He termed the blood groups as A, B, C. Later C was changed to
O.
2. What is the hallmark feature of the ABO blood group system?
- Carbohydrate dependent blood group system.
- Pre-formed IgM antibodies in the circulation that is effective in activating complement.
Give Ag to corresponding Ab then IVH occurs in vivo. Can be fatal.
- Most clinically significant blood group system
- High antigen expression of red blood cells, soluble forms in plasma of secretors.
3. What class of enzymes are involved in the ABO blood group system?
- Glycosyl transferases
4. What enzyme is associated with the addition of blood group A vs B vs AB vs O blood
groups?
- Blood group A: N-acetylgalactosylaminyl transferase
- Blood group B: Galactosyl transferase
- Blood group AB: Both N-acetylgalactosylaminyl transferase and Galactosyl transferase
- Blood group O: Fucosyl transferase (Note H antigen must be added first before A or B
antigen can be added: precursor structure).
5. What enzyme defines H blood group antigen? Why is it important? How do we test
for H antigen?
- Fucosyl transferase. Precursor structure added to backbone. H antigen detected by Ulex
Europeaus lectin.
6. What is the pattern of inheritance of the ABO blood group system?
- Autosomal codominant
7. What enzyme defines the Se gene? What proportion of the Caucasian population
carry the Se gene? If you carry the Se gene, what is the significance?
- Fucosyl transferase. 80% Caucasian population carry the Se gene. If you carry the Se
gene you can have soluble forms of blood group antigen in the plasma and saliva.
8. What are the features of the Bombay blood group? How is it relevant in transfusion
practise?
,- hh genotype: No H antigen expressed, phenotypically blood group is O but with
haemolytic anti H, anti A and anti B in the plasma. A Bombay person should only get
blood from another Bombay individual or from themselves (frozen blood that is
reconstituted).
9. For each ABO blood group indicate what red blood cell antigens are on the surface of
red blood cells and what antibodies are in the plasma.
- Blood Group A: A Ag on rbcs, anti B in plasma.
- Blood Group B: B Ag on rbcs, anti A in plasma.
- Blood Group AB: A and B Ag on rbcs, no anti A or anti B in plasma
- Blood Group O: No A or B Ag on rbcs, anti A and anti B in plasma
10. What phenotypes would be produced from a father group A and mother group B?
- AA or AO + BB or BO= AB, AO, BO, OO blood groups of offspring.
11. What are the phenotype frequencies in the Caucasian population for each of the ABO
blood groups?
- Blood Group O pos: 38% - O neg 7%
- Blood Group A pos: 32% - A neg 6%
- Blood Group B pos: 12% - B neg 2%
- Blood Group AB pos: 4% - AB neg 1%
12. What is the ABO blood group system so clinically important?
- Preformed IgM antibodies in the circulation, can bind to corresponding Ag if
incompatible blood is given, activate classical pathway of complement and cause
intravascular haemolysis.
- Highly expressed rbcs antigens, soluble forms in plasma and saliva
13. Give three examples of ABO blood group discrepancies that affect the forward and
reverse blood group.
- Forward blood group ABO discrepancies: A or B subgroup, HSCT,
- Transfusion mixed field A given O rbcs
- Reverse blood group ABO discrepancies: Rouleaux, cold reacting IgM antibody,
Bombay blood group, newborn, elderly.
14. How do we interpret ABO blood grouping by tube technique vs CAT technique?
- Tube technique 0-12 scale of assessing haemagglutination; CAT technique 04 scale of
assessing haemagglutination. Reactions with anti A, anti B and anti AB in forward group,
reverse group reactions with A1 cells, B cells and O cells.
15. Who discovered Rh blood group system? What were the observations made?
,- 1939 Levine and Stetson; 1940 Karl Landsteiner and A.S. Weiner. They observed that
85% of Caucasian population agglutinated with an antibody in rabbits to Macacus rhesus
red cells. This was shown later to be anti D.
16. How is Rh blood group system inherited?
- Rh blood group system is inherited by two genes RHD and RHCE. They are inherited as
haplotypes.
17. What is the Fisher and Race nomenclature?
18. Explain the inheritance of Rh alleles?
19. Describe the Rh polypeptide.
- Multipass polypeptide, 6 extracellular loops, crosses membrane 12 times, no sugars.
, 20. What is weak D? How would we identify that a donor or recipient is a weak D
phenotype in the laboratory?
- Weak D: RhD variant: missense mutations that affect transmembrane or cytoplasmic
region of RhD polypeptide resulting in less RhD antigen expressed on the surface of red
blood cells.
- Serologically Weak D may appear as RhD positive (weaker reaction) or as RhD negative
with IgM reagent but weakly positive with blend reagent IgM/IgG anti D in IAT phase.
Majority don’t make allo anti D. Donor: RhD positive: Recipient: RhD positive.
21. What is partial D? How would we identify that a donor or recipient is a partial D
phenotype in the laboratory?
- Partial D is a RhD variant. Missense mutations that affect the extracellular loops of RhD
polypeptide or hybrid where portions of RhD are replaced by RhCE. Serologically, can
be RhD positive (weaker reaction) or RhD negative by IgM anti D but weakly positive
with blend IgM/IgG anti D. Often picked up in a person who types as RhD positive but
appears to also have allo anti D in their plasma. Partial D often make allo anti D.
Pregnant women should be given RhIg to avoid RhD alloimmunisation. Donor: RhD
positive, Recipient: RhD negative.
22. What is the clinical significance of a partial D in pregnancy and in transfusion?
- Pregnant women should be confirmed as a partial D by molecular genotyping and given
RhIg to avoid RhD alloimmunisation. Donor: RhD positive, Recipient: RhD negative for
transfusion.
23. What is G antigen? How would we prove that a pregnant woman has anti-G?
- G is a combination antigen found on rbcs in the Rh blood group that carry D or C antigen.
It is absent when D and C are absent. RhD negative patients can produce anti-G following
transfusion of RhD negative, C positive red blood cells. Anti G is clinically significant to
cause HTR and HDFN.
Week 1 Lectorial Plan-ABO and Rh blood group systems.
Questions:
1. Who discovered the ABO blood group system? What were the observations made
that helped determine the ABO blood group system?
- Karl Landsteiner 1901. Won Nobel Prize for the discovery. Karl was working in Vienna
and he collected blood from colleagues and let the plasma and red blood cells separate by
gravity. He then mixed different plasmas with red blood cells and noticed different
patterns of agglutination. He termed the blood groups as A, B, C. Later C was changed to
O.
2. What is the hallmark feature of the ABO blood group system?
- Carbohydrate dependent blood group system.
- Pre-formed IgM antibodies in the circulation that is effective in activating complement.
Give Ag to corresponding Ab then IVH occurs in vivo. Can be fatal.
- Most clinically significant blood group system
- High antigen expression of red blood cells, soluble forms in plasma of secretors.
3. What class of enzymes are involved in the ABO blood group system?
- Glycosyl transferases
4. What enzyme is associated with the addition of blood group A vs B vs AB vs O blood
groups?
- Blood group A: N-acetylgalactosylaminyl transferase
- Blood group B: Galactosyl transferase
- Blood group AB: Both N-acetylgalactosylaminyl transferase and Galactosyl transferase
- Blood group O: Fucosyl transferase (Note H antigen must be added first before A or B
antigen can be added: precursor structure).
5. What enzyme defines H blood group antigen? Why is it important? How do we test
for H antigen?
- Fucosyl transferase. Precursor structure added to backbone. H antigen detected by Ulex
Europeaus lectin.
6. What is the pattern of inheritance of the ABO blood group system?
- Autosomal codominant
7. What enzyme defines the Se gene? What proportion of the Caucasian population
carry the Se gene? If you carry the Se gene, what is the significance?
- Fucosyl transferase. 80% Caucasian population carry the Se gene. If you carry the Se
gene you can have soluble forms of blood group antigen in the plasma and saliva.
8. What are the features of the Bombay blood group? How is it relevant in transfusion
practise?
,- hh genotype: No H antigen expressed, phenotypically blood group is O but with
haemolytic anti H, anti A and anti B in the plasma. A Bombay person should only get
blood from another Bombay individual or from themselves (frozen blood that is
reconstituted).
9. For each ABO blood group indicate what red blood cell antigens are on the surface of
red blood cells and what antibodies are in the plasma.
- Blood Group A: A Ag on rbcs, anti B in plasma.
- Blood Group B: B Ag on rbcs, anti A in plasma.
- Blood Group AB: A and B Ag on rbcs, no anti A or anti B in plasma
- Blood Group O: No A or B Ag on rbcs, anti A and anti B in plasma
10. What phenotypes would be produced from a father group A and mother group B?
- AA or AO + BB or BO= AB, AO, BO, OO blood groups of offspring.
11. What are the phenotype frequencies in the Caucasian population for each of the ABO
blood groups?
- Blood Group O pos: 38% - O neg 7%
- Blood Group A pos: 32% - A neg 6%
- Blood Group B pos: 12% - B neg 2%
- Blood Group AB pos: 4% - AB neg 1%
12. What is the ABO blood group system so clinically important?
- Preformed IgM antibodies in the circulation, can bind to corresponding Ag if
incompatible blood is given, activate classical pathway of complement and cause
intravascular haemolysis.
- Highly expressed rbcs antigens, soluble forms in plasma and saliva
13. Give three examples of ABO blood group discrepancies that affect the forward and
reverse blood group.
- Forward blood group ABO discrepancies: A or B subgroup, HSCT,
- Transfusion mixed field A given O rbcs
- Reverse blood group ABO discrepancies: Rouleaux, cold reacting IgM antibody,
Bombay blood group, newborn, elderly.
14. How do we interpret ABO blood grouping by tube technique vs CAT technique?
- Tube technique 0-12 scale of assessing haemagglutination; CAT technique 04 scale of
assessing haemagglutination. Reactions with anti A, anti B and anti AB in forward group,
reverse group reactions with A1 cells, B cells and O cells.
15. Who discovered Rh blood group system? What were the observations made?
,- 1939 Levine and Stetson; 1940 Karl Landsteiner and A.S. Weiner. They observed that
85% of Caucasian population agglutinated with an antibody in rabbits to Macacus rhesus
red cells. This was shown later to be anti D.
16. How is Rh blood group system inherited?
- Rh blood group system is inherited by two genes RHD and RHCE. They are inherited as
haplotypes.
17. What is the Fisher and Race nomenclature?
18. Explain the inheritance of Rh alleles?
19. Describe the Rh polypeptide.
- Multipass polypeptide, 6 extracellular loops, crosses membrane 12 times, no sugars.
, 20. What is weak D? How would we identify that a donor or recipient is a weak D
phenotype in the laboratory?
- Weak D: RhD variant: missense mutations that affect transmembrane or cytoplasmic
region of RhD polypeptide resulting in less RhD antigen expressed on the surface of red
blood cells.
- Serologically Weak D may appear as RhD positive (weaker reaction) or as RhD negative
with IgM reagent but weakly positive with blend reagent IgM/IgG anti D in IAT phase.
Majority don’t make allo anti D. Donor: RhD positive: Recipient: RhD positive.
21. What is partial D? How would we identify that a donor or recipient is a partial D
phenotype in the laboratory?
- Partial D is a RhD variant. Missense mutations that affect the extracellular loops of RhD
polypeptide or hybrid where portions of RhD are replaced by RhCE. Serologically, can
be RhD positive (weaker reaction) or RhD negative by IgM anti D but weakly positive
with blend IgM/IgG anti D. Often picked up in a person who types as RhD positive but
appears to also have allo anti D in their plasma. Partial D often make allo anti D.
Pregnant women should be given RhIg to avoid RhD alloimmunisation. Donor: RhD
positive, Recipient: RhD negative.
22. What is the clinical significance of a partial D in pregnancy and in transfusion?
- Pregnant women should be confirmed as a partial D by molecular genotyping and given
RhIg to avoid RhD alloimmunisation. Donor: RhD positive, Recipient: RhD negative for
transfusion.
23. What is G antigen? How would we prove that a pregnant woman has anti-G?
- G is a combination antigen found on rbcs in the Rh blood group that carry D or C antigen.
It is absent when D and C are absent. RhD negative patients can produce anti-G following
transfusion of RhD negative, C positive red blood cells. Anti G is clinically significant to
cause HTR and HDFN.
