Lecture 17/18 - Blood transfusion

Question 1

Red cell antigens: what are they composed of, how many groups are there, how many are recognised by ISBT, and which groups are the most clinically relevant?

Answer 1

Surface antigens composed of glycoproteins or glycolipids

~400

30 systems recognised by the International Society of Blood Transfusion (ISBT)

ABO and Rh groups.

Question 2

ABO blood group inheritance: which genes encode the ABO antigens and which genes/alleles are dominant/recessive?

Answer 2

Chromosome 9

Autosomal dominant inheritance - three allelic genes, A, B and O:
* Alleles A and B - co-dominant
* Allele O - recessive to both A and B

Question 3

What antigens are present in which ABO blood groups?

Answer 3

Each produces specific glycosyltransferases

They add sugars to a basic precursor substance (a basic antigenic glycolipid or glycoprotein) on the red cell membrane = H substance

Enzymes add single carbohydrate residues

• O - no effect on H substance, Terminal fucose
• A - N-acetyl galactosamine (GlcNAc)
• B - D-galactose (Gal)
• AB - N-acetyl galactosamine (GlcNAc)/D-galactose (Gal)

Question 4

Subtypes of A: what are they, how frequent is each displayed, and what is their difference?

Answer 4

A1: ~80%
A2: ~20%

• The A1 gene can create approximately 1 million A1 antigens in red cells
• The A2 gene results in the production of only 200,000 A2 antigens in red cells.

Question 5

The Bombay Phenotype: what is it, when was it first discovered, and what clinical complications are caused by this phenotype?

Answer 5

The incapability to form -2-L-fucosyltransferase (necessary for H substance formation), resulting in a lack of H substance expression

1st described in India in 1952

They produce antibodies to H substance and A/B antigens - Individuals with the Bombay phenotype can only be transfused with blood from other Bombay phenotype individuals

Question 6

The general distribution of blood groups

Answer 6

• O - most common
• A - second most common
• B - third most common
• AB least common

South America - only O present(?)

Question 7

Universal donors/recipients: what groups fall under these categories and what complications may they have?

Answer 7

Blood group O - universal donors (theoretical (excluding Rh groups))

Blood group AB - universal recipients

However, group O people have anti-A and anti-B in their plasma - in a small percentage of group O individuals these antibodies may be very potent, and agglutination may occur

Question 8

Rh blood groups: how many main antigens are there, how many rarer antigens are there, how was it discovered, what genes exist,

Answer 8

Five main antigens (C, c, D, E and e) - the MAIN antigen is D (either present (+) or absent (-))

other rarer antigens (up to 49 in total!).

Named after the Rhesus monkey - in 1940, Landsteiner and Weiner used an 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 proteins with the D antigen (and variants)
* RhCE gene - encodes the RhCE protein with the C, E, c and e antigens (and variants)

There is no d antigen - the D antigen si either present or absent

Question 9

Rh group D inheritance: how does it work and how does it link with ABO blood groups?

Answer 9

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 - Rh+ is dominant and Rh- is recessive

ABO and Rhesus genes are not linked and are inherited independently

Question 10

Rh group CcEe inheritance

Answer 10

This can result in one of four variations of the C, c, E and e antigens:
* CE
* Ce
* Ec
* ce

Question 11

Rh group D CcEe inheritance

Answer 11

This can result in one of eight variations of the C, c, E and e antigens:
* DCE
* DCe
* DEc
* Dce
* dCE
* dCe
* dEc
* dce

Question 12

Rₒ subtype: what is it, how frequent is it, how high demand is, and how common is it in certain backgrounds?

Answer 12

Dce - positive Rhesus group, they will always be A/B/AB/O+

Rare and in demand - 3% of the regular blood donors in England have the Ro subtype

Demand is increasing by 10-15% each year

> x10 as common in individuals from Black African/Black Caribbean/Mixed Heritage backgrounds

Question 13

Rh subtypes

Answer 13

• Rₒ
• R₁
• R₂
• Rz
• r
• r’
• r’’
• rᵧ

Question 14

Clinical importance of subtypes

Answer 14

When multiple blood transfusions are required, the risk of issues with acceptance may arise unless the exact subtype is used

Question 15

Rh antibodies: how does sensitisation occur?

Answer 15

Most are immune – result from previous transfusion or pregnancy (sensitisation)

Anti-D is of the most clinical significance

Anti-C, Anti-c, anti-E and Anti-e are occasionally seen

Question 16

(Rh) Haemolytic disease of the newborn: what is the process behind it, what was its prevalence in the past, and when should the treatments be used?

Answer 16

First pregnancy:
‘immune response’ towards the foetal Rh+ RBCs is formed, and anti-Rh antibodies are formed during delivery

Subsequent pregnancies:
Anti-Rh antibodies attack foetal RBCs, and HDN occurs

Haemolytic disease of the newborn (HDN) was a significant cause of fetal morbidity and mortality

Immunoprophylaxis with anti-D (RHO) immunoglobulin started being used - by 1990, decrease in mortality from 1.2 in 1000 births to 0.02 in 1000 births

Further reduction was achieved by introducing prophylaxis during the third trimester of pregnancy

The National Institute for Clinical Excellence (NICE) recommended that all Rh-negative pregnant women should be offered anti-D immunoglobulin routinely during the third trimester of pregnancy (NICE, 2002)

Question 17

Prevention of Rh immunisation - as a means to prevent HDN: what methods are there?

Answer 17

Antenatal Booking for all pregnant women ABO and Rh group -blood serum determined for antibodies at least twice during pregnancy

Pregnant women can be given Anti-D (RHO) immunoglobulin at various points during pregnancy and after birth - rationale for treatment: “Mop up” and destroy Rh-D positive fetal cells before they can sensitise the immune system of the mother to produce its anti-D antibodies

Question 18

Treatment of the mother during delivery: why may it be necessary and how does treatment occur?

Answer 18

Babies of Rh-negative women: ABO and Rh group found in the cord blood, haemorrhaging and blood loss used to estimate how much blood mixing occurred during delivery

• If the baby is Rh-negative, then the mother requires no further treatment
• If the baby is Rh positive, prophylactic anti-D is given, a minimum of 500 units i.m. within 72 hours of delivery

Question 19

ABO HDN: how does it occur, how frequent are ABO incompatibilities, and how frequent is it in the UK?

Answer 19

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 but not all result in HDN

~2% of all births, but severe haemolytic disease occurs in only 0.03% of births

Question 20

Research:
http://schizophrenia.com/prevention/rhcompat.html

interesting link to neuroscience (extra reading)

Question 21

COVID-19 and blood groups association? resreach -extra reading

Question 22

Blood transfusion timeline

Answer 22

1914: 1st successful human blood transfusion in Brussels

1937: 1st British Blood Bank open

1946: Launch of Blood Transfusion Service

1975: Glass transfusion bottles were replaced by plastic blood bags

Question 23

Blood transfusion: what is it, how is blood collected, and how many people donate blood?

Answer 23

Transfer of blood or blood-based products from one person into the circulation of another

Blood collected from a donor by aseptic technique into plastic bags that contain an anticoagulant

Annually in the UK: 2.1 million donations collected from about 1.6 million donors

Only 4% of the population, giving two or three times a year

Question 24

Blood transfusions - the journey of blood

Answer 24

• Donor - screened and sampled for blood group and viral testing
• NHS blood and transplant - components from whole blood manufactured
• Hospital blood bank - store units, cross match, designate units and label for recipient
• Ward
• Recipient - Prescription, positive patient identification, monitoring

Question 25

Manufacturing specific components from blood

Answer 25

Whole blood:
* Cellular components - RBCs, Platelets, WBCs
* Fresh plasma - fresh frozen plasma

Fresh frozen plasma:
* Cryosupernatant - Albumin, immunoglobulins, other concentrates
* Cryoprecipitate - Factor VIII concentrate

Question 26

Red cell transfusion: how much is one unit, how much does one unit increase haemoglobin, how long does transfusion occur for, how are the cells stored, and how long are they usable for?

Answer 26

~280ml, and is leucodepleted (no WBCs)

Each unit of red cells increases the Hb by
approx. 10g/l

Transfused over 2-4 hours

Storage: Temperature: 4°C +/- 2°C

Shelf-life: up to 35 days

Question 27

Transfusion donor/recipient: general process of transfusion

Answer 27

In an emergency (while blood groups are unknown) O- is used

Once the specific group is known, that is used instead

Question 28

FFP: what is it, how much is one unit, how is it manufactured, what does it contain, how specific is it, and how long does it last for?

Answer 28

Fresh frozen plasma

200-250ml

Prepared from anticoagulated whole blood by freezing to -30degcelc within 6 hours of collection

Contains all coagulation factors

Group specific

Shelf-life: up to 36 months frozen - 24 hours at 4oC after thawing

Question 29

Platelets

Answer 29

One adult dose of platelets =

‘pooled’ from 4 different platelet donations

Expected to increase platelet count by 20-40 x109

Shelf-life: 5 days

Question 30

ABO Forward and reverse grouping: how is the forward group tested and how is the reverse group tested?

Answer 30

Forward group:

Patients’ red cells are added to some columns, expression of antigens is tested

Reverse group:

Patients’ plasma is added to two columns (A1/B) and the blood is tested for anti-A/B antibodies

These tests are often done at the same time (?)

Question 31

The 4 phases for the supply of blood to hospitals: what are they and what do they indicate?

Answer 31

• Green - circumstances are normal and where supply meets demand
• Pre-Amber - reduced availability of blood for a short or a prolonged period
• Amber - reduced availability of blood for a short or a prolonged period which impacts on clinical activity
• Red - severe, prolonged shortages which impact clinical activity

Question 32

Top Users of blood

Answer 32

• Anaemia (medical) – 23%
• Orthopaedics – 14%
• Haematology – 15%
• Gastrointestinal bleeding – 11%
• General Surgery – 10%
• Cardiothoracic surgery – 6%
• Obstetrics & Gynaecology – 6%
• Vascular surgery – 5%
• Urology – 3%