Lecture 17/18 - Blood transfusion Flashcards
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?
Surface antigens composed of glycoproteins or glycolipids
~400
30 systems recognised by the International Society of Blood Transfusion (ISBT)
ABO and Rh groups.
ABO blood group inheritance: which genes encode the ABO antigens and which genes/alleles are dominant/recessive?
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
What antigens are present in which ABO blood groups?
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)
Subtypes of A: what are they, how frequent is each displayed, and what is their difference?
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.
The Bombay Phenotype: what is it, when was it first discovered, and what clinical complications are caused by this phenotype?
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
The general distribution of blood groups
- O - most common
- A - second most common
- B - third most common
- AB least common
South America - only O present(?)
Universal donors/recipients: what groups fall under these categories and what complications may they have?
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
Rh blood groups: how many main antigens are there, how many rarer antigens are there, how was it discovered, what genes exist,
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
Rh group D inheritance: how does it work and how does it link with ABO blood groups?
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
Rh group CcEe inheritance
This can result in one of four variations of the C, c, E and e antigens:
* CE
* Ce
* Ec
* ce
Rh group D CcEe inheritance
This can result in one of eight variations of the C, c, E and e antigens:
* DCE
* DCe
* DEc
* Dce
* dCE
* dCe
* dEc
* dce
Rₒ subtype: what is it, how frequent is it, how high demand is, and how common is it in certain backgrounds?
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
Rh subtypes
- Rₒ
- R₁
- R₂
- Rz
- r
- r’
- r’’
- rᵧ
Clinical importance of subtypes
When multiple blood transfusions are required, the risk of issues with acceptance may arise unless the exact subtype is used
Rh antibodies: how does sensitisation occur?
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
(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?
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)
Prevention of Rh immunisation - as a means to prevent HDN: what methods are there?
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
Treatment of the mother during delivery: why may it be necessary and how does treatment occur?
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
ABO HDN: how does it occur, how frequent are ABO incompatibilities, and how frequent is it in the UK?
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
Research:
http://schizophrenia.com/prevention/rhcompat.html
interesting link to neuroscience (extra reading)
COVID-19 and blood groups association? resreach -extra reading
Blood transfusion 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 were replaced by plastic blood bags
Blood transfusion: what is it, how is blood collected, and how many people donate blood?
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
Blood transfusions - the journey of blood
- 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
Manufacturing specific components from blood
Whole blood:
* Cellular components - RBCs, Platelets, WBCs
* Fresh plasma - fresh frozen plasma
Fresh frozen plasma:
* Cryosupernatant - Albumin, immunoglobulins, other concentrates
* Cryoprecipitate - Factor VIII concentrate
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?
~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
Transfusion donor/recipient: general process of transfusion
In an emergency (while blood groups are unknown) O- is used
Once the specific group is known, that is used instead
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?
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
Platelets
One adult dose of platelets =
‘pooled’ from 4 different platelet donations
Expected to increase platelet count by 20-40 x109
Shelf-life: 5 days
ABO Forward and reverse grouping: how is the forward group tested and how is the reverse group tested?
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 (?)
The 4 phases for the supply of blood to hospitals: what are they and what do they indicate?
- 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
Top Users of blood
- Anaemia (medical) – 23%
- Orthopaedics – 14%
- Haematology – 15%
- Gastrointestinal bleeding – 11%
- General Surgery – 10%
- Cardiothoracic surgery – 6%
- Obstetrics & Gynaecology – 6%
- Vascular surgery – 5%
- Urology – 3%
