Blood Products
Blood has many different functions in the body. This ranges from transport of vital substrates of cellular function, such as oxygen, and a major role in haemostasis.
As such, a number of different blood products may be needed by patients for different reasons when there is a problem with their own blood composition.
Blood products are pretty unique as a medicine as it is still not possible to manufacture many of these products, and so they are produced from processing of blood taken from donors. An understanding of this process is important to us when we think about blood products.
As such, a number of different blood products may be needed by patients for different reasons when there is a problem with their own blood composition.
Blood products are pretty unique as a medicine as it is still not possible to manufacture many of these products, and so they are produced from processing of blood taken from donors. An understanding of this process is important to us when we think about blood products.
Blood Donors
The majority of blood products still come from the processing of donated blood.
This means it has a production process that is quite different from usual medicines in order to ensure safety and quality due to the many potential hazards associated with this.
The European Union (EU) has set out very strict standards on the collection, processing and storage of human blood, and in the UK this is set out in law as the Blood Safety and Quality Regulations (BSQR) 2005.
There is also guidance from national and international bodies that goes beyond the details set out in law.
Unpaid donation is promoted by the World Health Organisation (WHO), and is the case in the UK, as this population have been shown to have the lowest risk for transmitted infections.
There is then subsequent careful selection of would-be donors to exclude those who would be high risk.
This is done by a questionnaire, focusing on topics such as medical history, travel history, drug use, and personal history, such as sexual practice.
People are not allowed to donate if they have significant health problems (e.g. cardiac disease), or recent activity with a risk of acquisition of a significant tranmissable infection e.g. recent tattoos.
People can donate from age 17, with no upper limit on age for regular donors, but requiring a full annual health review. The upper age for first time donors is 65 though.
This means it has a production process that is quite different from usual medicines in order to ensure safety and quality due to the many potential hazards associated with this.
The European Union (EU) has set out very strict standards on the collection, processing and storage of human blood, and in the UK this is set out in law as the Blood Safety and Quality Regulations (BSQR) 2005.
There is also guidance from national and international bodies that goes beyond the details set out in law.
Unpaid donation is promoted by the World Health Organisation (WHO), and is the case in the UK, as this population have been shown to have the lowest risk for transmitted infections.
There is then subsequent careful selection of would-be donors to exclude those who would be high risk.
This is done by a questionnaire, focusing on topics such as medical history, travel history, drug use, and personal history, such as sexual practice.
People are not allowed to donate if they have significant health problems (e.g. cardiac disease), or recent activity with a risk of acquisition of a significant tranmissable infection e.g. recent tattoos.
People can donate from age 17, with no upper limit on age for regular donors, but requiring a full annual health review. The upper age for first time donors is 65 though.
The donation process for whole blood involves cannulation of a large vein and in general removal of 450ml +/- 10% of blood (no more than 15% of the estimated blood volume).
The first 20ml of blood is diverted to try and remove any bacteria that may have been present on the skin entering the blood bag.
Similarly, the skin is cleaned well before cannulation to try and minimise the risk of blood contamination.
The first 20ml of blood is diverted to try and remove any bacteria that may have been present on the skin entering the blood bag.
Similarly, the skin is cleaned well before cannulation to try and minimise the risk of blood contamination.
Testing
There are a number of steps in the testing process with donated blood, again as a safety feature.
Potential donors have an initial semi-quantitative test of their haemoglobin level. This is either with a gravimetric method (a drop of capillary blood in a copper sulphate solution) or with portable haemoglobinometers.
The haemoglobin thresholds for donation are 135 g/L for men and 125 g/L for women.
All donated blood then undergoes a number of tests to look for transmissible infections:
However, there is still a risk of transmissible infections being missed by such tests, particularly if during the window period after initial infection, hence the importance of the history.
Potential donors have an initial semi-quantitative test of their haemoglobin level. This is either with a gravimetric method (a drop of capillary blood in a copper sulphate solution) or with portable haemoglobinometers.
The haemoglobin thresholds for donation are 135 g/L for men and 125 g/L for women.
All donated blood then undergoes a number of tests to look for transmissible infections:
- Syphilis
- Hepatitis B
- Hepatitis C
- HIV
- HTLV 1
However, there is still a risk of transmissible infections being missed by such tests, particularly if during the window period after initial infection, hence the importance of the history.
There is also non-infective testing of the blood:
There are additional specific tests for blood that will be needed for very specialised indications e.g. intrauterine transfusion, haemoglobinopathy patients.
- ABO group
- Rhesus antigens – D, C, E, c, e, K
- Haemoglobin S
- Atypical red cell alloantibodies
There are additional specific tests for blood that will be needed for very specialised indications e.g. intrauterine transfusion, haemoglobinopathy patients.
General Processing
During donation the blood is collected in a bag containing citrate, phosphate and dextrose (CPD) anticoagulation.
The citrate binds to the calcium ions needed for the coagulation process and hence stops the process.
The blood is then transported under strict temperature control for processing into the different components within 24 hours.
This is achieved through centrifugation, which separates the components based on their density and size:
The preservatives SAGAM (Saline, adenine, glucose and mannitol) are added to maintain RBC viability and it is stored at 4oC for up to 35 days.
The citrate binds to the calcium ions needed for the coagulation process and hence stops the process.
The blood is then transported under strict temperature control for processing into the different components within 24 hours.
This is achieved through centrifugation, which separates the components based on their density and size:
- Bottom layer – Red blood cells
- Middle layer – The ‘Buffy Coat’ containing platelets and white blood cells
- Top layer – Plasma
The preservatives SAGAM (Saline, adenine, glucose and mannitol) are added to maintain RBC viability and it is stored at 4oC for up to 35 days.
Platelets
Platelets are collected in one of 2 ways:
They are stored at 22 +/- 2oC with constant agitation for up to 5 days.
There is a fairly significant risk of bacterial growth in these storage conditions so bacterial screening tests and pathogen inactivation processes have been introduced in some places to help with this.
- From apheresis from a single platelet donor
- From pooling of the buffy coat from several donors
They are stored at 22 +/- 2oC with constant agitation for up to 5 days.
There is a fairly significant risk of bacterial growth in these storage conditions so bacterial screening tests and pathogen inactivation processes have been introduced in some places to help with this.
Plasma
After removal from whole blood, plasma is frozen at below -25oC.
At this temperature it can be stored for 36 months, though after thawing it has to be used within 24 hours.
For individuals born after 1996 (i.e. those who won’t have been exposed to dietary vCJD) plasma is imported from countries with a low risk of vCJD and treated with methylene blue.
At this temperature it can be stored for 36 months, though after thawing it has to be used within 24 hours.
For individuals born after 1996 (i.e. those who won’t have been exposed to dietary vCJD) plasma is imported from countries with a low risk of vCJD and treated with methylene blue.
Cryoprecipitate
Cryoprecipitate is created from thawed FFP which is again centrifuged and the supernatant taken off.
This creates a solution rich in the high molecular weight proteins such a fibrinogen, von Willebrand factor and factor VIII.
This is pooled into a pool of 5 units (each unit being 20ml). The adult dose for cryoprecipitate is 2 pools i.e. 10 units or 200ml.
This can also be stored at -25oC for up to 36 months, though it must be used within 4 hours once thawed.
This creates a solution rich in the high molecular weight proteins such a fibrinogen, von Willebrand factor and factor VIII.
This is pooled into a pool of 5 units (each unit being 20ml). The adult dose for cryoprecipitate is 2 pools i.e. 10 units or 200ml.
This can also be stored at -25oC for up to 36 months, though it must be used within 4 hours once thawed.
Further Processing
Leucodepletion
In the UK whole blood is passed through a leucodepletion filter before centrifugation to remove the WBCs, though in some places this is done at a later stage of the processing system.
This reduces the chance of WBC transmitted infections as well as certain transfusion related reactions.
Irradiation
In some case, blood products are irradiated by 25-50 Gyr.
This inactivates any viable lymphocytes in the product and is needed for those at risk of transfusion graft vs host disease e.g. immunocompromised patients.
This does shorten the shelf life of products though.
Pathogen reduction technology
This aims to treat the blood to further minimise the risk of transmissible infection.
Methylene blue treatment is one of the oldest examples of this.
A small quantity of methylene blue is added to a unit of plasma.
This is then exposed to visible light which results in oxidative free radical production that damages the nucleic acid of any encapsulated viruses or bacteria.
Octaplas is an alternative to this process.
Octaplas involves pooling of donations from patients in countries with low vCJD risk.
This pooling helps standardise the concentration of clotting factors present and dilutes the viral load of any infected donor blood, preventing transmission of hep A and parvovirus B19.
It also uses a solvent detergent treatment to inactivate bacteria, lipid enveloped viruses and most protozoa.
Some other systems are used in countries other than the UK to treat platelets, which are at particular risk of bacterial contamination.
These include the Intercept and Mirasol systems which involve adding substance to the platelets before exposure to UV light, producing damage to the DNA/RNA of pathogens.
In the UK whole blood is passed through a leucodepletion filter before centrifugation to remove the WBCs, though in some places this is done at a later stage of the processing system.
This reduces the chance of WBC transmitted infections as well as certain transfusion related reactions.
Irradiation
In some case, blood products are irradiated by 25-50 Gyr.
This inactivates any viable lymphocytes in the product and is needed for those at risk of transfusion graft vs host disease e.g. immunocompromised patients.
This does shorten the shelf life of products though.
Pathogen reduction technology
This aims to treat the blood to further minimise the risk of transmissible infection.
Methylene blue treatment is one of the oldest examples of this.
A small quantity of methylene blue is added to a unit of plasma.
This is then exposed to visible light which results in oxidative free radical production that damages the nucleic acid of any encapsulated viruses or bacteria.
Octaplas is an alternative to this process.
Octaplas involves pooling of donations from patients in countries with low vCJD risk.
This pooling helps standardise the concentration of clotting factors present and dilutes the viral load of any infected donor blood, preventing transmission of hep A and parvovirus B19.
It also uses a solvent detergent treatment to inactivate bacteria, lipid enveloped viruses and most protozoa.
Some other systems are used in countries other than the UK to treat platelets, which are at particular risk of bacterial contamination.
These include the Intercept and Mirasol systems which involve adding substance to the platelets before exposure to UV light, producing damage to the DNA/RNA of pathogens.
References
- L Green et al. Modern banking, collection, compatability testing and storage of blood and blood components. Anaesthesia. 2015. 70 (suppl 1.): 3-9.
