19. Blood Transfusions Flashcards
red cell antigens
Surface antigens composed of glycoproteins or glycolipids
Approximately 400 red cell group antigens described
30 blood group systems recognised by ISBT (international society of blood transfusion)
Most clinically relevant groups are the ABO and Rhesus groups used to type for blood transfusion
The other blood grouping systems only become important when an individual has received a blood transfusion and they may then be exposed to other foreign antigens which they recognize and then instigate an immune response
ABO system
1901: Dr Karl Landsteiner
Serum from group B individuals agglutinated group A red blood cells
Antibody to A antigens was present in group B serum.
Serum from group A individuals agglutinated group B red cells,
Antibody to B antigens in group A serum.
Serum from group O individuals agglutinated A and B cells
Antibodies to both A and B in group O serum. Groups A, B and O were the first groups discovered by Landsteiner.
ABO blood group inheritance
Theory for the inheritance first described by Berstein in 1924.
Genes encoding the ABO antigens: chromosome 9
Autosomal dominant inheritance
ABO system consists of three allelic genes, A, B and O.
Alleles A and B are co-dominant and
Allele O is recessive to both A and B.
inheritance of ABO groups test say the genotype and blood type of offspring if parent alleles are mum A dad B mum B dad A mum B dad O mum O dad O
genotype AB AB BO OO blood type AB AB B O
ABO Antigens
ABO genes:
produce specific glycosyltransferases
add sugars to a basic precursor substance (H substance)
Combined to lipids/proteins on the red cell membrane.
Controls the synthesis of enzymes that are responsible for the addition of single carbohydrate residues.
O gene - no effect on H substance = Terminal fucose – group O
N-acetyl galactosamine (GlcNAc) is added for group A
D-galactose (Gal) is added for group B.
These genes control the synthesis of enzymes that will then add single carbohydrate residues , we start off with H substance and then what is then added on will affect the blood group
blood groups (types) based on
specific antigens (= proteins, = agglutinogens) on surface of RBCs
O has no antigens
AB has A and B antigens
ABO blood group systems: naturally occurring antibodies
are not present at birth, but develop at early formation years of baby in response to foodstuffs and the environment
depending on what the individuals are exposed to, this will have an impact on the number and strength of the antibodies produced
eg group b has B antigens, so anti A antibodies
blood group antigen and antibody
type A, antigen A, antibody is anti-B
type B, antigen B, antibody anti A
type AB, antigen A and B, antibody is none
type O, antigen is neither, antibody is antiA and anti B
subtypes of A
1911: two different A antigens (A1 and A2 ) described.
A1: approximately 80%
A2: remaining 20%
A1 gene can create approximately 1 million A1 antigens on red cells.
The A2 gene results in the production of only 200,000 A2 antigens on red cells.
the Bombay phenotype
Extremely rare but interesting!
1st described in India in 1952
Incapable of forming -2-L-fucosyltransferase necessary for formation of H substance
Lacks expression of H substance
They produce antibodies to H substance as well as to A and B antigens
Individuals with Bombay phenotype can only be transfused with blood from other Bombay phenotype individuals.
Inherited defect
Cant form the h substance which is the precursor for adding on the sugars
Will type as an o person, will appear like they’re blood group o
universal donor and recipient
Blood group O: universal donors (theoretical)
However group O people have anti-A and anti-B in their plasma.
Small percentage group O individuals these antibodies may be very potent
What might happen in recipient?
Group AB: universal recipients as they do not have any anti-A or anti-B.
what about rhesus Rh factor - an extremely important consideration
by introducing whole blood we get plasma which has antibodies, which is why we separate into components eg rbc
The Rh Blood Group System
All antigens of the Rh blood group system
consists of five main antigens (C, c, D, E and e)
other rarer antigens (up to 49 in total!).
Named after the Rhesus monkey
1940: Landsteiner and Wiener
antibody produced in rabbits after the injection of red cells from the Rhesus monkey
DNA analysis: Two genes exist: RHD and RHCE.
RHD gene: encodes protein with the D antigen (and variants)
RHCE gene which encodes the RhCE protein with the C, E, c and e antigens (and variants)
There is no d antigen
D will cause the biggest immune response if incorrect transfusion. there is no little d antigen
Two genes exist: RHD & RHCE
Main antigens are D, C, E, c and e – encoded by the two adjacent loci
RHD gene: encodes protein with the D antigen (and variants)
RHCE gene which encodes the RhCE protein with the C, E, c and e antigens (and variants)
There is no d antigen
Lowercase d – denotes absence of the D antigen (gene usually deleted or non functional)
inheritance
The D antigen is inherited as one gene (RHD) -dominant
The Rh(D) antigen is inherited on the short arm of chromosome 1 with two alleles of which Rh+ is dominant and Rh- is recessive.
If both of a child’s parents are Rh negative, the child can only be Rh negative.
Otherwise the child may be Rh positive or Rh negative
ABO and Rhesus genes are not linked and are inherited independently.
rhesus genotypes
genotype and Rh(D) status cde/cde negative CDe/cde positive CDe/CDe positive cDE/cde positive CDe/cDE positive cDE/cDE positive
ABO Blood Group Rh(D) Type Percentage of Population
total O is 44% total A is 42% total B is 10% total AB is 4% total rh positive is 83% total rh negative is 17%
Red cell antigens and antibodies
if you have cell antigens A, naturally occurring antody produced is anti B and if cell antigens B naturally occurring antibody is anti A
if AB not antibodies
if O then anti A and anti B naturally occurring antibodies
if rhesus D no antibody
if rhesus cde/cde ie Rh negative, then you do not produce naturally occurring antibodies but do produce antibodies after sensitisation (atypical or immune)
(If u were to introduce a foreign antigen into an individual these will be antibodies that an individual will produce
But if you were to transfuse a rhesus negative person with rhesus positive blood they would then be sensitized and those would be antibodies theyd produce
However the more blood that an individual is transfused with they will be introduced to more and more antigens because we will all have the different numbers of different red cell antigens
Exposed to more red cell antigens with more transfusions
Can be at risk of developing these antibodies)
HDN
haemolytic disease of the newborn
rh negative mother and rh positive foetus
first pregnancy: during delivery Rh antigens enter mothers circulation through breaks in the placenta
mother makes anti Rh antibodies
Subsequent: mother has anti Rh antibodies
antiRH antibodies cross the placenta and destroy fetal blood cells
haemolytic disease of the newborn
Covered last year
The mismatch between mum and foetsu r polus and r negative interactions
Mum is r- and pregnant with r+ foetus
Mum doesn’t have d antigen but baby does
Shouldn’t be mixing of blood during pregnancy,
Delivery – rhesus antigens can enter mums circulation and introduce a response form mum so she makes anti D antibodes, now present in her circulation
No risk ot baby as its been delivered within 72 hours and mum takes 72 hours to surmount a complete immune response
These anti d antibodies were made by the mum, so stay present in circulation
If she were to become pregnant again, delivery blood mixes, antibodies can cross placenta and attack rbc of foetus within the period of labour. If at any point in pregnancy and there is trauma bloods can mix in utero, severe impact on babies rbc
As baby is r+, causes clumping of rbc so they break down, baby anaemic and blood vessels blocked as they have D antigen so anti d antibodies bind to the antigen
HDN reduction
Prior to 1970: HDN due to anti-D significant cause of morbidity and mortality.
By 1990, reduction in mortality from 1.2 / 1000 births to 0.02 / 1000 births achieved - immunoprophylaxis with anti-D immunoglobulin
Further reduction achieved by introducing prophylaxis during the third trimester of pregnancy
National Institute for Clinical Excellence (NICE) recommendation that all D-negative pregnant women should be offered anti-D immunoglobulin routinely during the third trimester of pregnancy (NICE, 2002).
HDN due to other blood groups? Yes but quite rareWe don’t know what babies blood type is until its born so if rhesus negative mother we assume abby is rhesus positive
ABO HDN
Restricted almost entirely to group A or B babies born to group O mothers with immune anti-A or anti-B antibodies.
Statistically, mother and infant are ABO-incompatible in 1 in every 5 pregnancies
In the UK: ABO HDN is about 2% of all births, but severe haemolytic disease occurs in only 0.03% of births
why does it only cause a problem in a small number of cases
Why: anti-A and anti-B antibodies are usually IgM – don’t cross the placenta, BUT
Sometimes antibodies that are IgG are produced - have the ability to cross the placental barrier
Limited by:
A or B antigens can be found on many different cell types in the fetus, thus leaving fewer antibodies available for binding onto fetal red blood cells
Red blood cell surface A and B antigens are not fully developed during gestation and therefore the numbe of antigenic sites is smaller on detail red blood cells
Universal Donor and Recipient (red blood cells)
Blood group O Rh negative: universal donors (red blood cells)
Group AB positive: universal recipients
Always transfuse own blood group once it is known
Blood transfusion: a timeline
1914: 1st successful human blood transfusion in Brussels
1937: 1st British Blood Bank open
1946: Launch of Blood Transfusion Service
1975: Glass transfusion bottles replaced by plastic blood bags
blood transfusion
Transfer of blood or blood based products from one person into the circulation of another
Blood collected by aseptic technique into plastic bags that contain an anticoagulant
Prior to use ABO and Rh status are determined
Processed and separated into components before use
In UK: Approx 2 million donations per year
Less than 3% of the population actively give blood, giving two or three times a year
the preparation of blood components from whole blood
whole blood separated into cellular components (and then to rbc platelets wbc) and fresh plasma (to fresh frozen plasma further split into cryoprecipitate (factor VIII concentrate) and crysupernatant (albumin, immunoglobulins, other concentrates)
