Transfusion - ABO Group Flashcards
What are ‘never events’?
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’
Talk about the severity of an ABO mismatch
Can be fatal -> as little as 50mls of ABO mismatched blood can cause a fatality
Leads to kidney failure and eventually death
What is different about group O antibodies compared to group A and B?
The group O antibodies (anti-A and anti-B) are both IgM and IgG
Group A and B only have IgM antibodies
Whaat is significant about having IgG antibodies?
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
What percentage of antigen expression do we have as babies?
Only 25% expression
Why is antigen expression so low after birth?
-> what is one of the reasons
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
What eould the outcome be if a person had an A allele on 1 of their chromosomes but an O allele on another chromosome?
Person will express A antigen i.e. they will be group A
What combination of parents could produce offspring of any ABO type?
AO and BO parents
What are the two main ways tha a group AB can occut?
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
What antigen does the O allele code for?
The O allele doesnt coe for anything
O allele does not encode any additional antigen i.e. cells will just have H antigen
What is the H antigen?
The substrate on the red cell on which the A and B antigen are built on
How common is the H antigen?
Almost every single person has this
Very very rare to not have a H antigen
Only seen in certain families -> very few in Ireland
Talk about how Oh is inherited (Bombay phenotype)
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
Talk about anti-H antibody
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
Write about the historical background of the ABO blood group
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
What did Karl Landsteiner do?
Defined three blood groups A, B and C
- defined A, B and C agglutination phenomena
When did Karl Landsteiner define the three ABO blood groups?
1901
Who were Karl Landsteiners students and what did they do?
Von Decastello and Sturli
They added a fourth group to the three system A, B, C group, later known as AB in 1902
Who were Karl Landsteiners students and what did they do?
Von Decastello and Sturli
They added a fourth group to the three system A, B, C group, later known as AB in 1902
In what year did Von Decastello and Sturli define the AB group?
1902
What further addition was made to the ABO blood group after the work of Landsteiner and his students?
In 1930 Thomsen et al extended the three alelle theory (A, B, O) to four (A1, A2, B and O)
When was the ABO system first put into use?
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
On what chromosome is the ABO gene located?
Chromosome 9
On what chromosome is the H gene located?
Chromosome 19
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
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
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+
What blood group system antibodies are activators of complement?
ABO
Duffy
Kidd
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
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
What might be a telltale sign a person has high titre anti-AB?
Haemolysis
No normal reverse group reactions, just haemolysis
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
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
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
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
What does the H locus encode?
An alpha1,2 fucosyltransferase caled FUT1
What does the H locus encode?
An alpha1,2 fucosyltransferase caled FUT1
What is the role of FUT1?
It creates ‘H’ active structures in erythroid tissues
What is the role of FUT1?
It creates ‘H’ active structures in erythroid tissues
What does the A locus encode?
alpha 1,3 N-acetylgalactosaminyl transferase
What does the A locus encode?
alpha 1,3 N-acetylgalactosaminyl transferase
What does the B locus encode?
An alpha1,3 galactosyltransferase
What does the B locus encode?
An alpha1,3 galactosyltransferase
What does the secretor gene encode?
An alpha 1,2 fucosyltranserase known as FUT2
What does FUT 2 do?
It is active in tissues such as gut epithelia and salivary glands
Makes antigens present insecretions
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
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
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
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
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
What amino acids form the catalytic site in group A
Leucine (@266) and glycine (@268) -> in both A1 and A2
What amino acids form the catalytic site in group B?
metionine (@266) and alanine (@268)
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
What is the gene product and immunodominant sugar of the H antigen?
Product = L-fucosyltransferase
Sugar = L-fucose
What is the gene product and immunodominant sugar of the A antigen?
Product = N-acetylgalactosaminyltransferase
Sugar = N-acetylgalactosamine
What is the gene product and immunodominant sugar of the B antigen?
Product = D-galactosyltransferase
Sugar = D-galactose
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
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
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
Is A1 and A2 encodes by the same gene?
No separate genes
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
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
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
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
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
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
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
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
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
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
What is the most common source of de-acetylase enzymes
Gut bacteria which infiltrate thr blood from a gastric adenocarcinoma
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
How does the Oh phenotype result
A nucleotide change in FUT1 which results in an inactive enzyme and no H antigen
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
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
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
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
What conditions tend to weaker ABO antigen expression
Leukaemias
Carcinomas
Alcoholics
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
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
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
Talk about coronavirus and ABO group
Group O are less suceptible to SARS
Group A tend to suffer from the worst infections
How many new blood groups have been introduced this year?
2 new blood groups this year to make a total of 47
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
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
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
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
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
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
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
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
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
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
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
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
What plasma can group O get?
A or B or AB Octaplas
i.e. universal plasma recipient
What plasma can group O get?
A or B or AB Octaplas
i.e. universal plasma recipient
What plasma can group B get
AB or A Octaplas (plasma that doesnt contain anti-B)
What plasma can group A get
AB or B Octaplas (plasma that doesnt contain anti-A)
What octaplas can AB receive?
ONLY AB
Universal plasma donor
What octaplas can AB receive?
ONLY AB
Universal plasma donor
What is the order of platelet preference to give a group O indivual?
O, A, B or AB
O = universal recipient of platelets
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
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
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
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
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
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
What are some symptoms of an ABO mismatch?
(7)
Intravascular haemolysis
Complement pathway activation
Hypotension
Vasodilation
Vasoconstriction
DIC
Renal failure
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
What ABO mismatch has the highest chance of killing someone?
Group A to group O
