Author - Dr Gail Miflin

Testing 1-[2]-3

Part 2 – Screening for infections

Screening blood for infections sounds very simple but the more you know about it the less simple it becomes…..

So, to start with, on every donation we test for some ‘mandatory’ markers. The fact that they are mandatory mean that we will not routinely issue the blood before the results are available and if they are positive then the blood cannot be issued through our computer system. Currently we test for Hepatitis B and C, HIV, HTLV (human lymphotrophic leukaemia virus), and syphilis. We can do tests that either look for evidence of the virus itself or we can look for antibodies in response to a previous infection or both. The techniques we use determine the ‘specificity’ and ‘sensitivity’ of the tests which means how often a positive result will be missed and how often a false positive result will be given. Also it is possible for a donor to be infectious but the infection is below the level of detection of the test even when the tests are done correctly. Even with both of these, the chance that an infectious donation enters the supply chain is really extremely small (less than 1 in several million depending on the virus) and even then this doesn’t necessarily mean that it will transmit an infection. But all of this is why we ask donors the questions about lifestyle behaviours and travel eg to minimise the risks to patients.

Even though people receiving blood usually worry most about transmission of a viral infection it is transmission of a bacterial infection that worries me more. Bacteria are most likely to grow in platelet transfusions as they are kept at a nice warm room temperature. The worry is particularly with bacteria that come from the skin and those from the gut because if they were to be transfused to someone with a reduced immune system, such as someone having chemotherapy, as they could cause a serious infection.

As you would expect we also have a number of processes in place to minimise the chances of bacteria being transmitted. This starts with the questions we ask donors about infections, through cleaning of the arm with antiseptic solution, a pouch for sample collection which takes the first draw of blood (containing the skin plug from the middle of the needle which could contain bacteria), the temperatures we transport our donations at, the sterile closed systems we use for processing, the testing that we do through to the inspections hospitals do on packs prior to transfusion. In addition we screen all our platelets for bacteria so the chances of any packs of platelets containing bacteria is also extremely low. With all of these in place, a pack of platelets that could potentially cause an infection getting to the hospitals occurs less than once a year on average – which is much lower that it was ten years ago.

So, as if all of this is not enough, we also do a number of ‘discretionary’ or optional tests on donations. These are tests done either because of the information a donor gives us or because we need products with additional tests done on them for certain patients. An example for patients is CMV (cytomegalovirus) tests where products given to new born babies and pregnant mothers are tested to ensure that they are CMV negative. Transmission of this virus, whilst very common and relatively harmless in the general population, can cause real problems in developing babies. An example of extra tests that are done because of donor information is West Nile Virus on people who have been on holiday in areas where the infection occurs (including common European destinations and the USA). Similarly malaria tests are done after travel to malarial risk areas and extra hepatitis B test are done for anyone who has had a tattoo or other piercings from 4 months after it was done.

Finally we have a duty of care to all of our donors which means that whenever we find a donor with a positive test result we will let you know and ensure that you are sent for the right NHS care. A few times every year testing positive for a test can potentially save a life – we hear of donors who have gone to their GP and been diagnosed with a serious illness such as bowel cancer they had no symptoms of after we have told them of their test results.

I hope this tells you two things – firstly a little bit about why we ask some of the questions that we do and secondly how hard we try to make our blood safe – using this work going on behind the scenes to ensure that transfusions in this country are among the safest, if not the safest, in the world.

Next time – tests in the future….

Testing [1]-2-3

If I had a pound every time I hear that someone has no idea of the amount of testing we do on the blood we collect and the sophistication of our labs then I would be out for a nice meal for two tonight. This is the first of three blogs where you can read about the kinds of things we do. This one is on routine blood cell testing, next will be infectious screening and the third about testing we may do in the future.
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As everybody knows we do some basic tests including the ABO and RhD blood groups which gives you the common shorthand of blood groups such as ‘O neg’. This is done on every donor every time you donate and actually includes the ABO group, the full Rh group and Kell blood group system in addition. On a number of donors we do additional testing for more red cell antigens and this can include a smaller panel of extra antigens (extended typing) done automatically by machine or indeed up to a very extensive panel (rare typing) done by our RCI (Red Cell Immunohaematology) labs or our IBGRL (International Blood Group Reference Laboratory) which are specialist laboratories staffed and led by some world class scientists. There are algorithms to decide which donations we test which antigens on and some times we screen donations specifically to look for a unit to transfuse to an individual patient. We always do these tests on donors from BAME background, on Ro donors and on very regular donors.
We used to have to do these tests on each donation if we wanted to put the results on the blood bag but since late last year as long as the tests have been done twice on a donor and are consistent then we can label every donation given with these details. This has reduced the need for testing considerably and enables us to save NHS money. Along with these tests we do a sickle cell test on all donations that have an extended red cell screen. This is because often these units go to patients with sickle cell disease and they already have too much sickle haemoglobin so transfusing a unit from a donor who has sickle cell trait would reduce the effectiveness of the treatment.
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Some of this additional screening enables us to source extremely rare units that we will freeze in our National Frozen Blood Bank. Sometimes we export these internationally to save the lives of patients abroad who need blood with these rare groups and are likely to die without a transfusion. Not all blood services maintain a frozen blood inventory but we do and ours covers all needs within the UK and we link with other groups in Europe and beyond to share information on what we have available.
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For apheresis platelet donors we test for certain white cell (HLA) and platelet (HPA) antigens and in female donors we test for antibodies as well. The antigens are on the surface of platelets or white cells and can be used for matching platelets when patients have developed antibodies against certain antigens in clinical conditions such as NAIT (Neonatal allo-immune thrombocytopenia) or a when a patient becomes unresponsive to platelet transfusions. There is more on this in my previous ‘Unsung Heroes’ blog. Occasionally the reagents needed for these tests are made from donations given by donors, in our Bristol clinic, who have rare antigens by taking an extra sample at the same time as donation. There are also some donors of red cells who are screened for HLA antigens because they have signed up to the British Bone Marrow Registry to potentially donate stem cells to someone requiring a stem cell transplant.
Finally in red cells and platelets that are destined for the very young (neonates) we also do a rather unforgettably named PANTS (Paediatric Antibody TestS) test on the donations to exclude some antibodies that could cause problems in these recipients.
The vast majority of our routine red cell testing is done on high throughput laboratory analysers which interface with our IT systems, automatically downloading results to the software and printing labels for the blood packs. We house these in Filton and Manchester which requires your samples to be transported to one of these centres by our logistics team. This team covers the whole country and joins up the whole supply chain, also helping deliver for other parts of the NHS. In Colindale we have a state-of-the-art NGS (Next Generation Sequencing) machine for testing HLA types by genetic methods rather than using traditional serological methods (using antibodies to detect antigens) and we expect to use this type of technology more in the future.
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We are so confident that the results we put on the blood pack labels are correct that hospitals in the NHS are not required to retest the blood and in many instances will be able to do an ‘electronic cross match’ on the patient who is due to receive the blood. Traditionally the blood in the pack and the blood from the patient’s pre-transfusion sample were always ‘mixed’ or cross-matched to confirm compatibility prior to transfusing. Now there are guidelines about when units can be selected as a match by laboratory IT systems, after the testing of the patients samples, confirming that the products are suitable to give. This confidence in our systems prevents the duplication of testing and reduces this within the NHS as a whole.
This testing of blood cells and antibodies however is just the beginning – we also routinely test for viruses and bacteria, with extra tests for donors who have been abroad to certain destinations. Some of these tests enable you to donate when in the past we would have asked you not to come or even sent you away if you had turned up. In addition all of these tests improve the safety of the blood products we provide for hospitals and patients – more of which next time.

Kindness of Strangers

Apologies for not posting a blog recently – I sustained a head injury in a skiing accident at the beginning of March and have then spent seven weeks off work recovering.
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On the few occasions when I have experienced healthcare as a patient it has given me insights and lessons that I never could have learned as a doctor. I am of course indebted to the French rescue and medical teams who treated me and to family, friends and colleagues for support – but the most humbling experiences have been those where complete strangers have gone out of their way to do things for me that they didn’t need to. It wasn’t their job, it was just kindness and a desire to help others – such were the actions of the man who found me unconscious, the taxi driver who realised I had been discharged from hospital in the snow with no shoes and the airport employee who put me on a train, amongst others.
I offer this as an insight to those of you reading this who donate blood – I know the recipients cannot thank you themselves but I’m sure that they all feel the same kind of gratitude that I have. In some cases probably much more – especially when the blood was live saving. I’ve never fully appreciated this before when I have donated blood and I can’t even begin to imagine the thanks and gratitude felt towards donors of tissues and organs.
This week there has only been one story at NHSBT and that is Teddy’s Story – I hope you have seen it in the media – if you haven’t click here and also here and please share it on your own social media accounts. They are the most inspirational family who did an amazing thing in a dreadfully sad situation. I hope it inspires you to join the Organ Donor Register if you haven’t already – why not click here and sign up now if not.
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I will be back soon with a post on blood safety to let you know all the things that happen to your blood once you have donated it to ensure that our blood is as safe as possible for patients. Have a good Bank Holiday weekend.

Unsung Heroes

In many ways I consider our apheresis platelet donors to be our unsung heroes, they give a huge amount of time and effort donating platelets. We currently collect around 70% of our platelets by apheresis and make the rest by pooling the platelets from four whole blood donations. Each apheresis donation provides two or three units of platelets and takes around 90 minutes, donors can donate as frequently as two weekly although most do this monthly. These apheresis platelets are preferentially used for babies, children and young adults and for people who have become ‘resistant’ to platelets.
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The concept of becoming resistant to platelets is interesting and can be hard to treat. This means that the transfused platelets are destroyed by the patient’s immune system before they get a chance to work. It can have a number of different causes and often may occur if someone is very ill with a fever and infection. However if patients become resistant to several units of platelets it might be because antibodies have formed, especially if the person has received a lot of platelet transfusions. These patients commonly have had leukaemia treatment or bone marrow transplants or are multiply transfused for disorders where the bone marrow has failed. The antibodies are usually anti-HLA antibodies which form against antigens (proteins) on the surface of white cells and platelets. ‘HLA’ stands for Human Leucocyte Antigen. When antibodies form then the platelets given to a patient need to be compatible with their HLA type so that they don’t receive any HLA antigens that they don’t already have on their own white cells. Only apheresis platelet donations can be used for these patients.
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For platelets only two of the HLA antigens are important, these are called the A and B antigens and these are inherited as a pair – one set from your mother and one from your father. If both sets are the same then this is termed homozygous, if one of each set is the same and one different this is called half homozygote and if both sets contain different antigens then this is called heterozygote.
Donations from both homozygote and half homozygote donors are very useful as they can be given to a wide range of patients. Only around 1:200 people are homozygote and around 1:7 are half homozygote because there are so many different HLA types. Of patients provided with a complete HLA matched platelet donation around 35% of those are met by our 400 homozygote donors and a further 38% from our 2500 half homozygote donors ie nearly three quarters of requests are met by donations from around a quarter of our donors. So if you are one of these donors then your donations are especially useful as they can be matched to so many different patients – often we know when you are donating and we have already decided who needs your donation.
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There are also similar antibodies that can form against another antigen system called HPA or Human Platelet Antigens. These are most commonly a problem during pregnancy when a mother has a rare HPA type and makes antibodies which destroy the baby’s platelets leaving it at significant risk of bleeding. If this occurs in the baby’s head it can cause serious complications or even life long disabilities. This is called Neonatal Allo-Immune Thrombocytopenia or NAIT. Platelets from people who have this rare HPA type may be used for these babies either whilst they are still in the womb or when just born to prevent these complications.
As part of our aim to let donors know how useful you and your donations are to us we will be writing to donors who are either HLA homozygous or half homozygous to let you know this. So if you receive a letter then you will know that your platelets are particularly useful in the situations described above. We will be putting some FAQs on our website about this too. Most donors who have the rare HPA type should already be aware as we have sent you a leaflet in the past.
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If you haven’t received either of these then it certainly doesn’t mean your donations are not useful. They will just be being used in a different way – as mentioned above, your donations will preferentially be being used for babies, children or young adults or may by chance be a match for someone who requires HLA selected platelets or may simply be used for another sick patient. All will be saving or improving someone’s life. So please continue to donate platelets. If anyone reading this is interested in becoming a platelet donor then please speak to the nurse next time you donate blood for more information. And finally thank you to all of you who donate platelets – you are an especially dedicated and valued group of donors – we couldn’t do the work we do without you.

Re cycling

This year marks 30 years since I went off to university with my first bike. Since that time I have cycled to work pretty consistently and whenever the journey allowed. I know from the periods where I haven’t managed to do this how good it is for me – keeping me relatively fit, clearing my head on the way home and providing me with one of the few ways I can get exercise into my life nowadays. So this year my New Year’s Resolution is to do more of the things I know are good for me – but does this include donating blood?
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One of the questions that we would like to answer at NHSBT is whether or not giving blood is good for you. Whilst we know a little bit about this there are still some bigger questions to be answered.

There are two groups of people who we already know that donating blood is good for – first is those with a mutation in an iron handling gene potentially causing a disorder called Haemochromatosis – this causes too much iron to build up in the body and treatment is venesection (removing blood). If this is done in a hospital then the blood is thrown away however if done with us then we can use the blood for patients as it is collected under regulated conditions. The second is a small group of people that have blood that is a little bit ‘thick’ – this is caused by a high haematocrit (the number of cells in the blood with respect to the amount of fluid). This can be caused by smoking, alterations in testosterone levels and other benign causes. If the level gets too high it may also be treated with venesection by doctors. If the blood is very ‘thick’ and this is due to a problem in the bone marrow then unfortunately you cannot be a blood donor. Blood donation for both these groups of people mitigates and delays any potential problems relating to these issues which is not a bad thing. Some donors will not know they have these conditions.
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So what about other donors, perhaps like you?

We know that every year we have somewhere around 20-40 donors who get to know they have a serious condition earlier that they might have done if they didn’t give blood. This is in addition to the 200 people who find out that they have a serious infection (such as Hepatitis B or C, or HIV) every year and is due to a number of reasons; for example we have alerted people to a diagnosis of colon cancer both through failing the haemoglobin screening process and screening platelets for bacterial contamination – the identification of certain bacteria in a product can point to where they might have come from. Additionally from the haemoglobin screening process people may be alerted to a diagnosis of significant anaemia which may lead to a more serious diagnosis. I should note here though that the vast majority of people who fail the screening process are absolutely fine and it is related to blood donation (especially if you are a woman and this is in addition to menstrual periods), similarly so for those who have platelets that grow bacteria.
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Our manufacturing processes and testing processes can alert us to the fact that there are more white cells in a product that we would expect and every year we find a few donors who are diagnosed with a relatively slow growing leukaemia called Chronic Lymphocytic Leukaemia. Every couple of years we also hear of a more serious leukaemia being diagnosed. We also send letters to a handful of donors every month alerting them that there blood has been tested and that one of the results was abnormal so we recommend that this is retested by the GP. We don’t routinely follow up on the GP’s results but we know that some donors have a diagnosis as a result of this referral as you tell us.
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Thus most of this knowledge is through donors telling us about their diagnosis usually because it means they can no longer donate blood. We would like to trial collecting this information on a more formal basis to evaluate the worth of testing donor’s blood counts and will be doing this as part of the INTERVAL study. If you have had a blood count repeated by your GP and you get a letter in the next few weeks asking for permission to contact your GP to get information on the results then I would be very grateful if you would agree to this. I think it can provide us with really interesting information on the benefits of testing full blood counts on donors and I hope will inform our policy going forwards.
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However all of these are for pretty small numbers of donors, since nearly a million people donate blood every year. What we would really like to establish is if there is any link to a reduction in rates of diabetes, cancer or heart disease from donating blood. In conjunction with the University of Cambridge, NHSBT is trying to establish if this might be the case. This will require linking of NHSBT data with GP databases by using NHS numbers to extract data and then unlinking and anonymising the records prior to analysis. We have ethical and research approval to do a pilot of 200,000 donors this year. This has the potential in a few years to answer the question which has been asked for a long time. In the future if we wish to do this with your data we will ensure we have your consent to do this.
I hope these endeavours will enable us to answer some of the bigger questions about whether donation might actually be good for you. In the meantime I will continue to donate blood and to cycle to work whenever I can.
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Finally thank you to all of you who have donated blood or platelets over the New Year period.