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Test Your Knowledge - ABO Blood Group System

A Blog from Eric Ching:
For some of us working at Canadian Red Cross in the 70’s before the first automated blood grouping instrument (remember BG15?!), we must have done tens of thousands of manual ABO/Rh typings on donors!
 
There was a motto among us: ”as easy as ABO”; the more I studied the subject, the more respect I have to our colleagues and scientists who continually provide more information to help us better understanding this seemingly straight forward but very complex subject indeed. I hope you’ll agree with me after playing the following game!
 
My suggestion: Please do a pre test and then look up references to become excellent on the subject.
Proceed with Caution: beware of some esoteric but interesting tidbits J
 
101 true or false questions on the ABO Blood Group System
 
        History
  1. The “Group C” first classified by Landsteiner was later replaced by “O” from the German word "one" meaning "without".
  2. Dr. Landsteiner was Group A.
  3. Landsteiner’s colleagues Alfred von DeCastello and Adriano Sturli identified group AB in 1902.
  4. The ABO blood group was proven to be an inherited autosomal dominant character by Watkin, Morgan and Kabat in 1924.
  5. A2, the weak subgroup of A, was first reported by Dungern and Hiszfeld in 1911; it was not until 40 years later, the A1 lectin from Dolichos biflorus was introduced by GWG Bird.
  6. The immunodominant sugars of ABH determinants were identified by Watkin, Morgan and Kabat in 1956.
  7. A3, when reacted with group B and group O sera, was first described by Friedenreich in 1936, as "very small clumps vastly outnumbered by unagglutinated cells".
  8. In 1980, Voak et al had demonstrated that monoclonal anti-A and anti-B could be used routinely in transfusion services.
  9. In 1990, the A and B specific transferases were cloned by Yamamoto and Hakomori in Seattle.
  10. ABO genotyping technology is available in many reference laboratories world wide.
Racial Distribution  
  1. A is less frequent among populations in northern and central Europe.
  2. A2 has a frequency of 10% among group A individuals in Asia.
  3. B is at least 2-3 times more frequent in central and south east Asia than Canada.
  4. The incidence of group O is much higher in Native American Indians, Africans and Australian aboriginals.
  5. Group O is the most common blood group worldwide.
 Genetics  
  1. The locus of ABO genes is at chromosome 19q34.
  2. Unlike other blood group systems, ABO and 6 of the currently known carbohydrate blood group systems (P1PK, Lewis, H, I, Globoside and FORS), are not coded by genes directly. The products of these genes are glycosyl transferases which are enzymes adding a specific sugar residue to form the oligosaccharide epitopes. For example, the A specific α 1-3 galactosyltransferase adds a molecule of galactose to the H precursor substance to form the A epitope.
  3. More than 50 amorphic alleles have been identified to account for group O phenotype as a result of a dysfunctional protein with no enzymatic activity.
  4. A group AB putative father can be directly excluded when both mother and baby are group O.
  5. The A and B consensus alleles are autosomal codominant and differ by only seven nucleotides and 4 amino acids.
 Biochemistry  
  1. Ceramide dihexose CDH aka lactosyl ceramide is the precursor of ABH and other carbohydrate blood group antigens.
  2. There are at least four precursor substances or peripheral core structures for A and B antigen to build onto.
  3. Monosaccharides D-galactose and N-acetyl-D-galactosamine can neutralize anti-A and anti-B respectively.
  4. Synthetic A and B substance were manufactured by Chem Biomed in Edmonton in the 1980’s.
  5. 90% of A or B antigens are covalently linked with glycoproteins such as Band 3, RhAG, glucose transporter and CHIP-1; the remaining 10% are linked to glycolipid and glycosphingolipid.
  6. The A and B glycosyltransferases are found in the cytoplasmic reticulum by adding a specific hexose to the precursor.
  7. A and B determinants on red cells are linked to Type 1 oligosaccharides.
  8. Concentrated B-transferase can add A-specific monosaccharide to form A determinant.
 Serology  
  1. Genetically A1 infants are reactive with A1lectin but not with human anti-A1.
  2. A and B antigens can be found in fetal blood as early as 5-6 week in gestation.
  3. Similar to other carbohydrate antigens, A and B antigens are hydrophilic and easily accessible by specific antibodies.
  4. B expression on cis-AB is weaker than normal AB but the reverse grouping is similar.
  5. Rare subgroups of B are more likely found in South American Indians.
  6. A1 red cells have around a million copies on each cell.
  7. While ABH antigens are present on red cells and platelets, leukocytes lack ABH. Lymphocytes adsorb ABH antigens from plasma in secretors only.
  8. A-transferase level may be lower during pregnancy.
  9. In-vivo deacetylation of N-acetylgalactosamine can be reversed by acetic anhydride in vitro.
  10. The Matuhashi-Ogata phenomenon describes the deacetylation of the A antigen by bacterial or viral deacetylase.
  11. Polyagglutination is not seen when monoclonal anti-A and anti-B reagents are used in developed countries.
  12. A and B antigens are found on almost all human tissues, hence termed “histo-blood group”.
  13. Although infants’ isoagglutinins can be detected as early as 3-6 months, serum concentration only reaches adult levels by age 2-4 years.
  14. Anti-A has a higher “titre” than anti-B among normal donors.
  15. Weak subgroups of A can be serologically classified by reactivity with anti-A and anti-A1, degree of H expression, reactivity with certain monoclonal anti-A,B, presence or absence of anti-A1 and presence of A and H in saliva.
  16. Although hemolysis is not seen when commercial reagent reverse grouping cells are used, it is a positive test when plasma is used with home made A1 and B cells suspend in saline without EDTA.
  17. Colostrum often contains more potent IgA anti-A and anti-B than in saliva .
  18. IgM anti-A is 100 times more powerful than IgG anti-A to agglutinate A cells; however, IgG anti-A is more heat resistant than its IgM counterpart.
  19. Yummy escargots have anti-A activity.
  20. Injection of group A urine elicited an increase of anti-A to 50% of the test subjects.
  21. Although less common, B lectin can be extracted from seaweed, salmon roe (Ikura is my favourite sushi!) and fungus.
  22. B lectin Griffonia simplicifolia also has Tk specificity.
  23. When ABO discrepancy is encountered, clerical and technical error must be ruled out before investigation.
  24. Unlike IgG antibodies to the Rh blood group system, IgG anti-A and anti-B are mostly IgG1and IgG2.
  25. Both Ael and Bel can adsorb and elute anti-A and anti-B respectively; however, A and B substance cannot be found in the saliva of secretors.
  26. A single molecule of IgG anti-A can activate the complement cascade.
  27. Although Ael is typed as O in forward grouping, reverse grouping is different than group O and the classical Bombay in that anti-B is stronger than anti-A.
  28. Mixed field reaction is seen with anti-A not only in A3 but also in Am, Ay and Ax.
  29. B(A) phenotype may be due to a mutation of the B transferase resulting in a small amount of A antigen to be present.
  30. B(A) cells are detected by ES-4 monoclonal anti-A at 2+ or less.
  31. It has been hypothesized that A(B) red cells are due to increased amount of H present causing A transferase to convert non specifically H to a small amount of B.
  32. Unbuffered MHO4 monoclonal anti-B had caused increased detection of acquired B.
  33. Mixed field reactions in the forward group can be observed in renal and bone marrow/stem cell transplantation, fetomaternal hemorrhage and in dizygotic twins.
  34. Extra reactions in both forward and reverse grouping may be seen in cryoglobulinemia and cold agglutinin syndrome.
  35. Extra reaction(s) in reverse grouping may be due to warm reactive autoantibody.
  36. Transfusion history and diagnosis often help to resolve ABO discrepancies.
  37. Polyagglutination such as T, Tn, Tk, etc. can still be seen when monoclonal ABO forward reagents are used.
  38. Some chimeras, BMT/BCT recipients and all reported Amos and Bmos individuals have two distinct ABO populations.
  39. ABO discrepant results are most frequently encountered in Waldenstrome’s macroglobulinemia.
  40. Red cells heavily coated with cold agglutinin can be correctly ABO typed by treating red cells with reducing agents such as 2ME, DTT and AET.
  41. Antibodies to compound antigens of A or B and Lewis are not uncommon but blood bankers don’t look for them in routine practice.
  42. IgG anti-A can be neutralized by A substance more readily than IgA anti-A.
  43. Minor ABO incompatible BMT/HCT recipients (e.g., O to A) may not have or very weak anti-A months or years following engraftment.
  44. Extra unwanted positive reactions in reverse grouping may occur when a room temperature reactive antibody to a low incidence antigen happens to be present on the reverse grouping cell. e.g., Mg
  45. Group O red cells transfused into group A recipients can adsorb A antigen only when the recipient is a secretor.
  46. A and B oligosaccharides present in milk and urine are linked to glycosphingolipid.
  47. Any non-group O patient who develops a positive DAT following IVIg therapy should be investigated by running the eluate against patient’s ABO identical reagent red cells.
  48. Rare auto anti-A and anti-B react equally well with adult and cord red cells.
 Bonus True Statement

Compare with Group AB, Cis AB, weaker forward grouping - A as A2, B as B3 in some but not all families, increased H expression. Reverse grouping - weak anti-B present.

Clinical Significance  
  1. In order to bypass the use of radio 51Cr-labelled red cells antigen positive cord red cell and Kleihauer-Betke can be used to determine red cell survival.
  2. Intravascular hemolysis of as little as 5 ml of red cells in a 70 kg patient will have a visible slight tinge of red in plasma of the post transfusion sample.
  3. C3a is 100 times more potent than C5a in causing vasodilation and contraction of smooth muscle.
  4. As little as 30 ml of ABO incompatible blood can cause a fatal hemolytic transfusion reaction.
  5. The risk of a fatal hemolytic transfusion reaction has been estimated to be 1 in 800,000.
  6. Investing resources in information technology to prevent ABO transfusion accidents has been minimal when compared with testing for infectious markers on donors.
  7. ABO incompatible transfusion accidents are asymptomatic in approximately 10% of patients.   
  8.  Immunosuppression and plasmapheresis have been successfully used to overcome major ABO incompatible organ rejection in young children less than three years.
  9. Major ABO incompatible stem cell and bone marrow transplant are routinely performed.
  10. ABO HDFN is usually milder because of low level maternal isoagglutinin of IgG 2 and 4 as well as immaturity of the glycosylated structure of fetal red cells. In addition, maternal isoagglutinins can be adsorbed by other fetal tissue cells.
  11. The incidence of clinically significant ABO HDFN is identical in premature and full-term infants.
  12. Research is being done on the use of bacterial exoglycosidases extracted from Elizabethkingia meningosepticum and Bacteriodes fragils to cleave the A and B determinant to O for safe transfusion and better inventory management.
  13. “Stealth red cells” are group A or B red cells which test as group O by using polyethylene glycol PEG to coat the antigens.
  14. Pegylated stealth red cells are non immunogenic and enjoy normal life span as untreated red cells.
  15. Progenitor blood forming units from group O, Kel 1 negative donors have been successfully cultured in liquid medium; reticulocytes and young red cells can soon be harvested for transfusion.
  16. Donors taking bacteria-based nutritional supplements may develop high-titred isoagglutinin which cause hemolytic transfusion reactions when a plasma containing blood component is given to a minor incompatible recipient. For example, group O to A platelet transfusion.
 Disease Associations  
  1. Misuse of statistics had lead to a report stating that “hangover” is more pronounced in group A people and group B people defecate the most!
  2. Illegitimate A and A like antigen can be found on malignant tissues in group O and group B patients.
  3. There are fewer peptic ulcers in A than O because there are fewer Leb receptor sites for Helicobacter pylori which has been shown to cause stomach ulceration.
  4. Group O individuals are more susceptible to enterotoxigenic E. coli and V. cholera infection.
  5. Group O individuals are less susceptible to Plasmodium falciparum infection due to a much weaker binding of parasites’s PfEMP1 than the A and to the lesser extent B antigen.
  6. Thrombotic disease is more common in O while bleeding is more common in A.
  7. Group O individuals have 25-30% higher von Willebrand Factor (vWF)  plasma level than non-O individuals.
  8. A and B antigens on the N-glycans of the vWF hinders the access of ADAMTS13 for plasma clearance resulting in higher incidence of thrombosis among non-O individuals.
  9. Group O individuals have higher risk of pancreatic cancer than group B.
Bonus True Statement:
Expression of ABH antigen may be associated with cell growth and migration demonstrable in tumor cells and wound healing.
 
Answers
 
1.     T
2.     F - Landsteiner was group O; his red cells were not clumped by any one of his colleagues’ sera.
3.     T
4.     F - suggested by Epstein and Ottenberg in 1908 and confirmed by von Dungern and Hirszfeld in 1910
5.     T
6.     T
7.     T
8.     T
9.     T
10.  F - only a handful of reference labs can perform ABO genotyping as the ABO genetics is very complicated.
11.  F - A is most frequent among populations in northern and central Europe.
12.  F - A2 is rare among group A individuals in Asia.
13.  T
14.  T
15.  T
16.  F - The locus of ABO genes is at chromosome 9q34.
17.  F  - Unlike other blood group systems, ABO and 6 of the currently known carbohydrate blood group systems (P1PK, Lewis, H, I,Globoside and FORS), are not coded by genes directly. The products of these genes are glycosyl transferases which are enzymes adding a specific sugar residue to form the oligosaccharide epitopes. For example, the A specific α 1-3 N-acetylgalactosaminyltransferase adds a molecule of N-acetyl galactosamine to the H precursor substance to form the A epitope.
18.  T
19.  F - A group AB putative father can be only be indirectly excluded when both mother and baby are group O. The first order of exclusion is the appearance of a marker that is absent in both mother and the putative father.
20.  T
21.  T
22.  T   
23.  F - Monosaccharides N-acetyl-D-galactosamine and D-galactose can neutralize anti-A and anti-B respectively.
24.  T
25.  T
26.  F - The A and B glycosyltransferases are found in the Golgi apparatus by adding a specific hexose to the precursor.
27.  F - A and B determinants on red cells are linked to Type 2 oligosaccharides.
28.  T
29.  F - Genetically A1 infants are non reactive with both A1lectin and human anti-A1.
30.  T
31.  T    
32.  F - B expression on cis-AB is weaker than normal AB but the reverse grouping is similar.
33.  F - Rare subgroups of B are more likely found in central and south east Asia while almost all South American Indians are non-B.
34.  T
35.  T
36.  T
37.  T
38.  F - The acquired B antigen describes the deacetylation of the A antigen by bacterial or viral deacetylase. The Matuhashi-Ogata phenomenon refers to the non specific adsorption of a second antibody to the antigen negative adsorbing red cells.
39.  T
40.  T
41.  F - Although infants’ isoagglutinins can be detected as early as 3-6 months, serum concentration can only reach to adult levels by age 5-10 years. ABH antigen are fully developed by 2-4 years.
42.  T
43.  T
44.  F - Although hemolysis is not seen when commercial reagent reverse grouping cells are used, it is a positive test when plasma is used with home made A1 and B cells suspend in saline without EDTA. Were you tricked?!
45.  T
46.  T
47.  T
48.  T
49.  T
50.  T
51.  T
52.  T
53.  T
54.  F - At least two IgG anti-A in close proximity whereby the two adjacent CH2 domains can anchor the C1q macromolecule. On the other hand, a single IgM molecule anti-A can fix complement.
55.  T
56.  F - Mixed field reaction is the hall mark of A3 red cells with anti-A only.
57.  T
58.  F - B(A) cells are detected by MH04 monoclonal anti-A at 2+ or less.
59.  T
60.  F - Unbuffered ES4 monoclonal anti-B had caused increased detection of acquired B. In a fatal transfusion accident, group AB units were given to an A recipient having acquired B. Transfusion 1996;36:351-357
61.  T
62.  T
63.  F - Extra reaction(s) in reverse grouping is most likely due to cold reactive autoantibody.
64.  T
65.  F - Polyagglutination such as T, Tn Tk etc. is not seen when monoclonal ABO forward reagents are used, because anti-T, Tk, Tn are found in normal human sera.
66.  T
67.  F - ABO discrepant results could be occasionally encountered in Waldenstrome’s macroglobulinemia
68.  T
69.  T
70.  F - A substance is more readily neutralized by IgA anti-A than its IgG counterpart.
71.  T
72.  T - This is the reason why some blood banks set up two A1 reverse group cells in their ABO discrepancy investigation.
73.  F - Group O red cell transfused into non group A recipient can also adsorb A antigen as A substance of type 2 precursor is found in the plasma. Secretor recipient has both type 1 and type 2 precursor in the plasma.
74.  F - A and B oligosaccharides present in milk and urine are simple oligosaccharide chains.
75.  T
76.  F - Rare auto anti-A and anti-B react less well with cord red cells than adult red cells.
77.  T
78.  T
79.  F - C5a is 100 times more potent than C3a in causing vasodilation and contraction of smooth muscle seen in acute hemolytic transfusion reactions and anaphylaxis due to anti-IgA in patients with severe IgA deficiency.
80.  T
81.  T - The risk of a fatal hemolytic transfusion reaction has been estimated to be 1 in 1, 800,000. Blood 2009;113:3406-17
82.  T
83.  F - ABO incompatible transfusion accidents are asymptomatic can be up to 50% of patients.     
             Immunohematology 2009;25:48-59
84.  T
85.  T
86.  T
87.  F - The incidence of clinically significant ABO HDFN is less in premature and termed infants. (Mollison P.668)
88.  T
89.  T
90.  F - Although Pegylated stealth red cells are non immunogenic , they have much shorter life span than normal red cells.
91.  F  - Progenitor blood forming units from group O, Kel 1 negative donors have been successfully cultured in liquid medium, reticulocytes and young red cells can soon be harvested for transfusion.
92.  T
93.  T
94.  T
95.  T
96.  T
97.  T
98.  F - see statement #100.
99.  F - Non-O individuals have 25-30% higher von Willebrand Factor (vWF)  plasma level than group O individuals.
100. T
101. F - Group B individuals have higher risk of pancreatic cancer than group O.
 
References
  • Daniels G. Human Blood Group. 3rd ed. Oxford:Wiley-Blackwell.2013
  • Garratty G ed. Immunobiology of Transfusion Medicine. New York:Marcel Dekker, Inc. 1993
  • Issitt PD Anstee JD. Applied Blood Group Serology. 4th ed. Durham NC Mongomery. 1998
  • Mollison PL. Blood Transfusion in Clinical Medicine. 5th ed. London: Blackwell. 1972
  • Race RR, Sanger R. Blood Groups in Man. 6th ed. Oxford:Blackwell.1975 
  • Reid ME, Lomas-Francis C. Blood Group  Antigens FactsBook. 2nd ed. San Diego: Academic Press. 2003
  • Story JR, Olsson MI. The ABO blood group system revisited. A Review and Update. Immunohematology 2009;25:48-59
Ranking
 
<50% - you have bad luck guessing
50-60% - you have good luck guessing
60-70% - average
70-80% - good
>80% - excellent

Please look up the references and try again; I hope you will get >80%!

I appreciate your feedback.

Eric
 

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