19. Blood Transfusions

Question 1

red cell antigens

Answer 1

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

Question 2

ABO system

Answer 2

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.

Question 3

ABO blood group inheritance

Answer 3

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.

Question 4

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

Answer 4

genotype 
AB
AB 
BO 
OO
blood type 
AB
AB
B
O

Question 5

ABO Antigens

Answer 5

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

Question 6

blood groups (types) based on

Answer 6

specific antigens (= proteins, = agglutinogens) on surface of RBCs

O has no antigens
AB has A and B antigens

Question 7

ABO blood group systems: naturally occurring antibodies

Answer 7

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

Question 8

blood group antigen and antibody

Answer 8

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

Question 9

subtypes of A

Answer 9

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.

Question 10

the Bombay phenotype

Answer 10

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

Question 11

universal donor and recipient

Answer 11

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

Question 12

The Rh Blood Group System

Answer 12

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

Question 13

Two genes exist: RHD & RHCE

Answer 13

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)

Question 14

inheritance

Answer 14

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.

Question 15

rhesus genotypes

Answer 15

genotype and Rh(D) status 
cde/cde negative 
CDe/cde positive 
CDe/CDe positive 
cDE/cde positive 
CDe/cDE positive
cDE/cDE positive

Question 16

ABO Blood Group Rh(D) Type Percentage of Population

Answer 16

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%

Question 17

Red cell antigens and antibodies

Answer 17

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)

Question 18

HDN

Answer 18

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

Question 19

haemolytic disease of the newborn

Answer 19

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

Question 20

HDN reduction

Answer 20

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

Question 21

ABO HDN

Answer 21

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

Question 22

why does it only cause a problem in a small number of cases

Answer 22

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

Question 23

Universal Donor and Recipient (red blood cells)

Answer 23

Blood group O Rh negative: universal donors (red blood cells)

Group AB positive: universal recipients

Always transfuse own blood group once it is known

Question 24

Blood transfusion: a timeline

Answer 24

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

Question 25

blood transfusion

Answer 25

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

Question 26

the preparation of blood components from whole blood

Answer 26

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)