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4.1 Transfusion and Transplant Immunology > Transfusion - ABO Group > Flashcards

Transfusion - ABO Group Flashcards

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1
Q

What are ‘never events’?

A

Events that should never happen such as an ABO mismatch
A person should never be transfused the wrong blood group
ABO mismatches are nearly always due to wbits
Haemovigilence deems these ‘never events’

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2
Q

Talk about the severity of an ABO mismatch

A

Can be fatal -> as little as 50mls of ABO mismatched blood can cause a fatality

Leads to kidney failure and eventually death

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3
Q

What is different about group O antibodies compared to group A and B?

A

The group O antibodies (anti-A and anti-B) are both IgM and IgG

Group A and B only have IgM antibodies

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4
Q

Whaat is significant about having IgG antibodies?

A

IgG antibodies can cross the placenta

This can cause a positive DAT for a baby -> could be one of the reasons why we have such low expression of antigens as babies -> if mother is group O but baby is group A then maternal anti-A IgG will cross the placenta and coat foetal rbcs causing a positive DAT

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5
Q

What percentage of antigen expression do we have as babies?

A

Only 25% expression

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6
Q

Why is antigen expression so low after birth?
-> what is one of the reasons

A

Reduce the affects of maternal antiobdies if aby is ABO incompatible i.e. group O mother and group A baby, anti-A IgG crosses placenta and causes positive foetal DAT

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7
Q

What eould the outcome be if a person had an A allele on 1 of their chromosomes but an O allele on another chromosome?

A

Person will express A antigen i.e. they will be group A

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8
Q

What combination of parents could produce offspring of any ABO type?

A

AO and BO parents

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9
Q

What are the two main ways tha a group AB can occut?

A

AB is mostly often times due to the inheritence of one A allele on one chromosome and one B allele on another chromosome

AB can much less frequently be due to the inheritence of a cisAB allele i.e. an AB allele on the one chromosome

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10
Q

What antigen does the O allele code for?

A

The O allele doesnt coe for anything

O allele does not encode any additional antigen i.e. cells will just have H antigen

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11
Q

What is the H antigen?

A

The substrate on the red cell on which the A and B antigen are built on

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12
Q

How common is the H antigen?

A

Almost every single person has this

Very very rare to not have a H antigen

Only seen in certain families -> very few in Ireland

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13
Q

Talk about how Oh is inherited (Bombay phenotype)

A

Only really seen in families where there has been cousins married etc etc

There must be an initial mutation which results in a damaged H gene -> this is passed down to offspring

If two offspring marry their offspring will have a chance of inheriting two copies of the damaged H gene which will result in no H antigen being produced

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14
Q

Talk about anti-H antibody

A

A lot of people have a cold anti-H, its quiet common

It is often the cause of cold agglutinins

It is not clinically significant -> it is benign

Its only really seen below 30 degrees

Just have to warm up sample to reduce interference when ABO typing etc

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15
Q

Write about the historical background of the ABO blood group

A

Initially defined by Karl Landsteiner in 1901
- He defined the A, B and C (later renamed O) agglutination phenomena in normal human blood in 1901

Von Decasello and Sturli added the AB blood group in 1902

Both observed the predictable presence of antibody to the missing antigen

Thomsen et al extended the three allele theory to A, B, O to four -A1, A2, B and O

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16
Q

What did Karl Landsteiner do?

A

Defined three blood groups A, B and C
- defined A, B and C agglutination phenomena

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17
Q

When did Karl Landsteiner define the three ABO blood groups?

A

1901

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18
Q

Who were Karl Landsteiners students and what did they do?

A

Von Decastello and Sturli
They added a fourth group to the three system A, B, C group, later known as AB in 1902

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19
Q

Who were Karl Landsteiners students and what did they do?

A

Von Decastello and Sturli
They added a fourth group to the three system A, B, C group, later known as AB in 1902

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20
Q

In what year did Von Decastello and Sturli define the AB group?

A

1902

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21
Q

What further addition was made to the ABO blood group after the work of Landsteiner and his students?

A

In 1930 Thomsen et al extended the three alelle theory (A, B, O) to four (A1, A2, B and O)

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22
Q

When was the ABO system first put into use?

A

First put into use in 1917 in WWI
Used to transfuse battlefield casualities in France
This was also the first use of ‘banked’, preserved blod
All were group O donations -> only men transfused on battlefield so no maternal antibodies etc

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23
Q

On what chromosome is the ABO gene located?

A

Chromosome 9

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24
Q

On what chromosome is the H gene located?

A

Chromosome 19

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25
In the ABO blood group, what genes are considered dominant vs recessive or silent
A and B genes are dominant i.e. if you have one copy you will express the antigen O is recessive i.e. you need two copies to be group O
26
Say a little about ABO antibodies in general
IgM in group A, B and O but also IgG in group O They are active at room temperature They are potent activators of complement They are clinically very significant They are predictably present in the plasma of most individuals
27
At what temperature do ABO antibodies react best
4 degrees -> if you have a weak reverse group it might be suggested to refrigerate the plasma for 30 mins and redo -> the reaction will usually increase from a 1+ to a 3+
28
What blood group system antibodies are activators of complement?
ABO Duffy Kidd
29
How frequent are ABO mismatches? How do they come about?
Only about 8 or 9 mismatches a year in the UK Only really seen with plasma products or WBITS
30
Why is it more common to see mistakes with plasma products?
Mistakes and confusion amongst clinical staff e.g. Clinical staff understand group O- blood can be given to anyone so they attempt to give group O- plasma to a patient not understanding that it contains both anti-A and anti-B e.g. A group B- patient requires platelets but no B- available, O- platelets given instead of A- platelets
31
What might be a telltale sign a person has high titre anti-AB?
Haemolysis No normal reverse group reactions, just haemolysis
32
What is anti-A,B?
An unusual/rare antibody seen in some group O individuals Its a single antibody that reacts with both the A antigen and the B antigen It often reacts better with weak subgroups of A
33
What induces the production of anti-ABO antibodies and what is this mechanism called?
ABO anibodies are produced against gut flora through molecular mimicry You produce antibodies against the gut flora that you do not have
34
What do the ABO alleles actually code for?
They code for the production of transferases These transferases catalyse the addition of saccharides to a precursor material on the rbc
35
What term can be used to describe the sugars added on by the ABO alleles and why is this?
They can be described as immunodominant This is because the additon of these sugars confer specific antigenic activity on the oligosaccharide chains -> not antigenic wihtout these sugars e.g. fucose for the H antigen
36
What does the H locus encode?
An alpha1,2 fucosyltransferase caled FUT1
37
What does the H locus encode?
An alpha1,2 fucosyltransferase caled FUT1
38
What is the role of FUT1?
It creates 'H' active structures in erythroid tissues
39
What is the role of FUT1?
It creates 'H' active structures in erythroid tissues
40
What does the A locus encode?
alpha 1,3 N-acetylgalactosaminyl transferase
41
What does the A locus encode?
alpha 1,3 N-acetylgalactosaminyl transferase
42
What does the B locus encode?
An alpha1,3 galactosyltransferase
43
What does the B locus encode?
An alpha1,3 galactosyltransferase
44
What does the secretor gene encode?
An alpha 1,2 fucosyltranserase known as FUT2
45
What does FUT 2 do?
It is active in tissues such as gut epithelia and salivary glands Makes antigens present insecretions
46
Describe what occurs in the production of a group B(A) phenotype
Mostly B (galactosyltransferase) but every now and then an N-acetyglactose will be added on Its a rare condition but will cause ABO abnomalies The transferase enzyme isnt just adding one sugar its adding both i.e. transferase not working properly
47
What is the structural difference between the A and B genes?
The A and B genes differ by 7 nucleotide changes This results in 4 key amino acid differences between A and B transferases
48
What is the structural difference between A antigen and 'O antigen'?
Group O results from a single base deletion at position 261 This deletion results int he formation of an early stop codan and therefore an iactive enzyme Group O can also result from other nucleotide changes that affect the catalytic site and therefore result in no demonstrable antigen
49
What is the structural difference between A antigen and 'O antigen'?
Group O results from a single base deletion at position 261 This deletion results int he formation of an early stop codan and therefore an iactive enzyme Group O can also result from other nucleotide changes that affect the catalytic site and therefore result in no demonstrable antigen
50
Explain what structurally happens to create an O2 group?
In O2 there is a single nucelotide deletion that introduces a reading framshift This results in leucine and argenine forming at the catalytic site however these have no demonstrable antigen so patient is classed as group O
51
What amino acids form the catalytic site in group A
Leucine (@266) and glycine (@268) -> in both A1 and A2
52
What amino acids form the catalytic site in group B?
metionine (@266) and alanine (@268)
53
What amino acids form the catalytic site in group O?
There is no antigen at all in group O => no catalytic site Early stop codon
54
What is the gene product and immunodominant sugar of the H antigen?
Product = L-fucosyltransferase Sugar = L-fucose
55
What is the gene product and immunodominant sugar of the A antigen?
Product = N-acetylgalactosaminyltransferase Sugar = N-acetylgalactosamine
56
What is the gene product and immunodominant sugar of the B antigen?
Product = D-galactosyltransferase Sugar = D-galactose
57
Talk about chain branching and age
You start of as a new born with a simple chain (i) As you age the structure of the chain starts to spread out more (I) You get an ABO antigen at the end of each branch Increased antigenicicity as you age
58
What does blood group I encode and where is this gene found
A gene on chromosome 6 encodes an I-transferase Beta-1,6-N-acetylglucosaminyltransferase
59
What are the two most important subgroups of A and how frequent are they?
A1 and A2 80% of people are A1 and 20% are A2
60
Is A1 and A2 encodes by the same gene?
No separate genes
61
How do you investigate an A2 subgroup?
Some people who are A2 will have an anti-B and and anti--A1 in their plasma e.g. Anti-A and anti-B coming up in reverse group React red cells with Dolichos biflorus -> if A1 cells present it will react
62
What is Dolichos biflrous
Its a lectin found in plant see extract Has the specificity of anti-A1 ->will react with A1 cells but not A2 cells
63
Talk a little about A and further subgroups of A
There is an A3 and other weaker forms of A These are rare alleles and only really evident when not paired with an A1/A2 allele If found these are usually treated as O
64
Talk about the presence of anti-A1 antibodies in A subgroups
Can be seen in A2 and A2B groups In the 20% of group A that are A2, 2% of these produce anti-A1 In the 20% of group AB that are A2B, 25% of these produce an anti-A1
65
What is the classification of weak A subgroups based on? (What 5 factors are used to classify all the different weak A subgroups?)
Degree of RBC agglutination by anti-A and ant A1 Degree of RBC agglutination by anti-A, B Degree of H reactivity of the RBCs Presence or absence of anti-A1 in the serum Presence of A and H substances in the saliva of secretors
66
What is a kind of telltale that you have an A3 or an A4 subgroup?
These tend to react more with the anti AB antibody
67
What phenomenom occurs in relation to antigen expression on AB cells
B antigen is usually less frequently expressed on rbcs when compared to expression of A antigen on group A rbcs However in group AB the B antigen tends to hold its own and there is equal expression of both A and B antigens
68
Talk about the secretor state
'Water soluble' ABH antigens in body fluids Glycoprotein in nature Influenced by the Secretor gene (FUT2) The property is sometimes used to confirm 'weak' subgroups of A and B Forensic possibilities About 75% of people are secretors
69
Talk about the acquired B phenotype
Not very common but can be seen in hospital laboratories Thi is where a group A individual acquires the group B phenotype through the work of de-acetylase enzymes The A antigen is essentially cut to become the B antigen
70
How does the acquired B phenotype usually present itself?
Strong reaction with anti A reagent but not anti-B (weak anti-B reaction) Reverse reaction is completely normal
71
What is the most common source of de-acetylase enzymes
Gut bacteria which infiltrate thr blood from a gastric adenocarcinoma
72
Talk about the Oh phenotype
Previously called the Bombay phenotype as it was first discrovered there Lack of H gene activity i.e. hh genotype Consequent lack of H transferase (FUT1) Leads to inability to synthesise H and or A/B antigens Red cells are otherwise normal
73
How does the Oh phenotype result
A nucleotide change in FUT1 which results in an inactive enzyme and no H antigen
74
What blood should be given to an Oh pateint?
Ideally any Oh patient should act as their own donor i.e. freeze their own blood for when they need it If own blood or family blood not available then O>A2>B>A2B>A1>A1B blood -> they will react with all donor blood that is not Oh as Oh will have an anti-A, anti-B and an anti-H
75
What are the four headings for when your writting an essay in an exam?
History of Group Antigens of Group Antibodies of Group Disease association
76
List some diseases and how they affect ABO blood groups
In leukaemia/carcinomas there is a weakening/loss of ABO In gastric adenocarcinoma -> acquired B Duodenal Ulcers more common in Group O individuals Gastric carcinoma is associated with group A Group O has the lowest vWF and FVIII HDFN in ABO incompatible mothers/foetus ABO antigens as histocompatibiltiy antigens on other cells and tissues -> rejection ABO and Sars CoV2
77
List some diseases and how they affect ABO blood groups
In leukaemia/carcinomas there is a weakening/loss of ABO In gastric adenocarcinoma -> acquired B Duodenal Ulcers more common in Group O individuals Gastric carcinoma is associated with group A Group O has the lowest vWF and FVIII HDFN in ABO incompatible mothers/foetus ABO antigens as histocompatibiltiy antigens on other cells and tissues -> rejection ABO and Sars CoV2
78
What conditions tend to weaker ABO antigen expression
Leukaemias Carcinomas Alcoholics
79
Talk about group O and duodenal ulcers
H-pylori uses the H antigen to attach to cells H-pylori causes ulcers Group O has the most H antigen -> and no other antigen to hide the H antigen from H. pylori => group O most affected by ulcers
80
Talk about ABO and FVIII and vWF
Group O has the least vWF so they are less likely to be pro-coagulant Less likely to have deep vein thrombosis etc etc
81
Talk about ABO antigens in transplants
Organs also have ABH antigens e.g. a group A liver ABO Incompatible (ABOI) transplants are now possible but treatment must be given to reduce antibodies so that the liver wont reject etc ABO tires are done frequently in beaumont hospital where there is frequent transplants
82
Talk about coronavirus and ABO group
Group O are less suceptible to SARS Group A tend to suffer from the worst infections
83
How many new blood groups have been introduced this year?
2 new blood groups this year to make a total of 47
84
Why was it found that groupA individuals were more susceptible to severe covid 19 infection?
It was found that anti-A in non group A individuals i.e. group B and O interfered with COVID This meant non-group A individuals were less likely to suffer from sever infection
85
How are blood group O affected by covid-19
rate of covid-19 positivty much lower in group O individuals type o may serve as a protective factor Blood type O less susceptiible to infection Blood type O asymptomatic at higher rates
86
How are blood group O affected by covid-19
rate of covid-19 positivty much lower in group O individuals type o may serve as a protective factor Blood type O less susceptiible to infection Blood type O asymptomatic at higher rates
87
Explain in detail how it is thought that the anti-A antibody protects against covid infection
Viral spike protein/angiotensin-converting enzyme 2 (ACE2) dependent adhesion to ACE-2 expressing cell lines was specifically inhibited by anti-A antibodies
88
Explain in detail how it is thought that the anti-A antibody protects against covid infection
Viral spike protein/angiotensin-converting enzyme 2 (ACE2) dependent adhesion to ACE-2 expressing cell lines was specifically inhibited by anti-A antibodies
89
How does ABO affect VWF? (3)
ABO blood group determines plasma von WIllebrand factor levels Blood group O individuals have reduced VWF survival - blood group affects ADAMTS ability to cut VWF and multimer size which affected half life of VWF ABO blood group direct influences VWF binding to PLT GPIb
90
How does ABO affect VWF? (3)
ABO blood group determines plasma von WIllebrand factor levels Blood group O individuals have reduced VWF survival - blood group affects ADAMTS ability to cut VWF and multimer size which affected half life of VWF ABO blood group direct influences VWF binding to PLT GPIb
91
How is VWF activated normally? (4)
VWF is first released as multimers These multimers must be broken down by ADAMTS family proteins into smaller multimers If these are not broken down the VWF will cause platelet aggregation This process is affected in group O individuals, they tend to have more multimers which results in 25% less VWF and VWF with a much shorter half life
92
Talk a little about the phenotypic variation of ABO population %s around the world
In caucasians O and A are most common In Blacks O and (much less frequently than caucasians) A are most common In orientals O is most common, A and B have similar rates In indian populations B is the most common followed by A then O, highest population of AB frequency as well In aboriginals, B blood group never developed, A and O only groups seen
93
Why is the frequency of different blood groups amongst certain populations an important consideration?
Certain antibodies seen in certain populations and no others e.g. Asia would see different antibodies then we would in Ireland
94
How is blood group distributed across ireland?
A+ most common in the east of the country due to influence of Vikings B more common in the west due to influence of Moores who came through africa and spanish sailing etc etc
95
What is meant by compatible blood? (3)
not the specific correct group given but wont cause a reaction -> should revert to correct ABO specifity as soon as its available -> not always possible e.g. with O-s -> low on O-s
96
What plasma can group O get?
A or B or AB Octaplas i.e. universal plasma recipient
97
What plasma can group O get?
A or B or AB Octaplas i.e. universal plasma recipient
98
What plasma can group B get
AB or A Octaplas (plasma that doesnt contain anti-B)
99
What plasma can group A get
AB or B Octaplas (plasma that doesnt contain anti-A)
100
What octaplas can AB receive?
ONLY AB Universal plasma donor
101
What octaplas can AB receive?
ONLY AB Universal plasma donor
102
What is the order of platelet preference to give a group O indivual?
O, A, B or AB O = universal recipient of platelets
103
What is the order of platelet preference to give a group B indivual?
B or AB platelets B will have some anti-A will will break down some of AB platelets but better than nothing
104
What is the order of platelet preference to give a group A indivual?
A or AB plasma A individual will have some anti-B which will affect AB platelets but better than nothing
105
What is the order of platelet preference to give a group AB indivual?
A or B or AB platelets They wont have any antibodies so any platelet type is suitable except O
106
What is the order of platelet preference to give a group AB indivual?
A or B or AB platelets They wont have any antibodies so any platelet type is suitable except O
107
Why should group O platelets never be given to anyone other than group O?
Unlike group O red cells, the group O platelets will still contain some of the anti-A and anti-B plasma If you give group O platelets to an A person the anti-A in the plasma will attact recipient red blood cells -> transfusion reaction Better of giving an A- patient B- platelets than O-platelets
108
How does an ABO mismatch occur and how do we prevent it?
Nearly always due to a WBIT 2 sample rule in place in nearly all hospitals (not MMUH) to prevent this Bloodtrack requires clinican to scan patient wrist band before printing stickers for tubes as well to ensure clinician is at bedside when labelling tubes -> what used to happen was nurse printed all labells at once and labelled after phlebotomy etc
109
What are some symptoms of an ABO mismatch? (7)
Intravascular haemolysis Complement pathway activation Hypotension Vasodilation Vasoconstriction DIC Renal failure
110
What is DIC, what are the stages, what are the symptoms?
First stage = over coagulating Second stage = anti-coagulated - bleeding - no factors left Causes bleeding under the skin/rash Immunecomplexes can block up the kidney which results in renal failure Hence dialysis maybe needed after an ABO mismatch
111
What ABO mismatch has the highest chance of killing someone?
Group A to group O

4.1 Transfusion and Transplant Immunology (24 decks)

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