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SA: Hello, and welcome to Master the MRCPCH. In this series, we tap into the expertise here at Great Ormond Street Hospital to give you an overview of a topic on the RCPCH exam curriculum. So whether you're revising for an exam or just brushing up on a need to know topic hopefully this podcast can give you the information that you need.
I'm Dr. Sarah Ahmed, a paediatric registrar and the current digital learning education fellow here at GOSH.
Today, we're talking to Dr. Anne Kelly about blood transfusion. Dr. Kelly is a consultant haematologist at Great Ormond Street Hospital and holds a number of national roles in blood safety, including working as an expert in paediatric and neonatal transfusion for NHS Blood and Transplant. We're going to be talking about blood transfusions, which maps to learning outcomes in the haematology and oncology section of the exam curriculum. This episode will be split into two parts. In part one, we're going to cover patient blood management, including safe prescribing and transfusion thresholds. In part two, we're going to discuss major complications, risk management and rules around taking consent.
This is part one. Join us next week for part two.
Anne thank you very much for talking with us today.
AK: No problem at all.
SA: So, we start all these podcasts off with some learning outcomes. So what would you like people to get out of listening to this?
AK: So I'd like people to have awareness of the current guidelines for prescribing blood products in babies and in children. I'd also like them to have some awareness about the reason why it's important that we get it right for these patient groups.
SA: Great. I'm sure we can cover all of that. So starting at the very beginning there's this phrase, patient blood management. Can you explain what that is and why is relevant to paediatrics or neonates?
AK: Yeah, definitely. So patient blood management is all about really getting transfusion right for children and babies. And it's a multidisciplinary evidence-based approach to optimizing the care of patients who need a transfusion. And a lot of it's very similar to in adults. For example, the use of tranexamic acid in patients having surgical procedures where they have a moderate chance of having a blood loss and that's really important for reducing the blood loss and reducing the need for transfusion. And then also use of things like cell salvage for surgical procedures, where appropriate.
But there are some specific things in paediatrics that I think is really important for us. So things like, for example delayed cord clumping in the neonatal period, minimizing sample volumes, only doing a test for a child if it's actually really necessary – blood's better off in the child rather than in the test tube. And then other sort of paediatric relevant things, particularly around prescribing. So we know for children by and large until they reach a certain size, we should be prescribing in mls. So it's getting that prescribing right and adhering to things that we we all know we should do in terms of transfusion thresholds and making sure we choose the right reason the transfusing a child.
SA: You spoke a little bit there about prescribing and thresholds. Can we go through and talk about some of the indications and thresholds and volumes for different transfusions in neonates, infants and children? That's quite a big question but let's work our way through it.
AK: Exactly. So I think if we maybe, if we split it first of all into, yeah, first of all, let's talk about neonates, and let's talk about thresholds. So the first thing to say is that by and large, your units are will have their own policy for transfusion. They should broadly be based on national guidance. And one thing which we should say as well, is that the current UK guidance for the whole of transfusion for children and babies is currently being revised. So there may be some change in the future. So just make sure that you're practicing to your current unit policy, which should be up to date and based on national guidance.
So for neonates, current guidance is based upon age of the child. And these are the thresholds really all around preterm babies. And we think that basically the more restrictive thresholds will be relevant then for term babies. And it really depends on what level of respiratory support the child is requiring. So you're looking at whether they're ventilated and whether they're on CPAP or whether they're off oxygen, off respiratory support. And then you're looking at what the postnatal age of the child is. So essentially that the earlier the child is after birth and the more respiratory support, the higher threshold. So for the first 24 hours, the threshold is generally 120 for a ventilated baby, that's 120 grams per litre of haemoglobin. Uh, CPAP or NIPPV about the same, and then for a baby off oxygen is 100. And then as the child gets older, we're able to relax those thresholds a bit. So between day one and seven, you can relax a bit, particularly in the babies who are not ventilated and the babies are ventilated the current recommendation is to keep a higher threshold, but in the babies who are not ventilated, you're looking at a threshold of a hundred. So the same as those who are off oxygen. And then once you go into week two, again, we relax further. So the ventilated baby threshold comes down to a hundred. The ones who are on CPAP, for example, down to 95, and the babies who are not on any respiratory support down to 75. And again, in week three, it goes down again. And I, I think the details, and we'll talk again at the end about some resources which will help you to remember the details of these different time points. Um, so that's the threshold for red cells in babies and the term babies generally, we're thinking about going for the more restrictive thresholds for the babies.
Then when we think about the volume, so there's not actually a lot of evidence out there in terms of what the right volume is. We'd recommend generally 15 mls per kilo. But where that figures come from over the time, there's not a lot of evidence for that. With regards to the threshold, there have been a couple of big trials recently in neonates, and that's the reason why the national guidelines is likely to change a little bit. And so watch this space for the change, particularly in neonatal thresholds.
So that's red cells in neonates. When we look at platelets in neonates again, we don't have a split by gestation of baby, but we have a split sort of by clinical situation and the neonatal thresholds are broadly based around the data from the Planet 2 trial, which I'm sure you'll all be aware of. Essentially what that gave us was a much more restrictive threshold for platelet transfusions of babies. So essentially for babies without bleeding including, you know, sick preterm babies, we're looking at a threshold of 25. And for babies with bleeding or before surgery and we also had a, we have a category for if they've had a previously affected sibling with intracranial bleed with NAIT, neonatal alloimmune thrombocytopenia, we say 50. And then for major bleeding or major surgery, we say a threshold of 100. So that's platelets and platelet volume, 10 to 20 mils per kilo.
FFP again I guess my key message for neonatal FFP is that we shouldn't be using FFP to routinely try and correct abnormalities of coagulation in babies who aren't bleeding. Point number one. Second point for FFP is to actually remember that the normal ranges are different in the neonatal period, so make sure that you're looking at age and gestation appropriate normal ranges. For babies who have clinically significant bleeding prior to invasive procedures who have clotting that's abnormal and significantly above the gestational and age-related normal ranges, then FFP may be indicated. The volume is generally 15 to 20 mls per kg for FFP.
And the final product that we need to talk about for neonates is cryo. So cryo is used really as a source of fibrinogen. So generally we're looking at a fibrinogen level of above 1 if you've got significant bleeding in a baby or you're having a procedure. And the dose of cryoprecipitate is 5 to 10 mls per kilo.
So lots of figures and lots of details there. And one of the key things I'll commend to you about all of these different figures is that actually there's a very good app. I know we're going to talk about resources at the end, but there's a very good app called the Blood Components App, which is available to download. And it has all these details on there, but just as I said before, just check it's aligned to what your unit specific policy is as well.
SA: Yeah, I do think it's worth going through it and talking about the numbers, even though it seems like Oh my gosh, so many numbers, but yes, we'll list lots of resources down below. And just to echo what you said, make sure you check your local guidelines as well.
AK: Exactly. Yeah. Perfect. Brilliant. So that's, that's neonates. And then when we move into infants and children, so let's first of all talk about red cells. So we know that there's lots of evidence for using a restrictive haemoglobin threshold in patients. So basically in stable, non-cyanotic patients, we're generally looking at a haemoglobin threshold of 70. Now the difference between neonates and infants and children is that generally when we're talking about a small child, we should, we should be using the transfusion formula to work out the exact volume you need for the child. So rather than just prescribing a flat mls per kilo for the child, it's better practice to use the formula. So what you would generally aim is for a haemoglobin no more than 20 grams per litre above where you started from. So for example, if you had a child that had a haemoglobin of 68, you'd aim for a haemoglobin of 88. And what you do is you basically you work out what rise you want for the child. So you have the desired haemoglobin, you take away the haemoglobin where you’re at at the moment, you multiply by the child's weight, and then you multiply by a factor. And a lot of units will use a factor of four, but again, look at your local policy as to what your team has decided to use. So multiply by four, and then you divide the whole lot by 10. And that gives you the volume in mils.
One thing I really critically I'd say, because all of us doing maths under pressure, one very useful and important thing to do is to do a quick check that you've not prescribed a completely crazy volume of blood for a child. Work out what 20mls/kilo is, which is kind of more like a ceiling of what one would give to a child as a top up transfusion. Work what that is and check that what you've prescribed is not more than that. And that will catch errors of factors of 10 and things if you've gone wrong on the formula.
SA: And get a friend to check, especially if it's the middle of the night.
AK: Exactly. Get someone else to check, especially if it's the middle of the night. And a lot of trusts have now moved to electronic prescribing. So you may find that your electronic prescribing system has some fail safe in there for you as well.
So that's the formula. The other thing to say as well is that once you get to more than one full red cell unit for a child, the best thing to do, unless you're obviously in a major haemorrhage situation, which is a whole different conversation, is to give a single unit to a child, because that's what we do in adults. We give a single unit and then we reassess with a blood count and work out where we've got to.
So that's the sort of thresholds and the volumes and how to work things out for red cells. The other thing to say is that that for some patients, they may have different thresholds. So, for example, haemoglobinopathy patients may require higher thresholds, so there is some patient specific and diagnosis specific nuance there. So, for example, a thalassemia patient, you're going to be aiming for a higher target, etc.
And the other thing to say is, as well, is that sometimes actually we may be able to avoid transfusion. So if, for example, a child is iron deficient and has been chronically iron deficient, as they mostly are, then actually a child can tolerate a haemoglobin very low 30, 40, et cetera, without symptoms. If they're not symptomatic then you can use iron instead of blood. And that's another thing about patient blood management. Another way to avoid blood transfusion for children is to correct anaemia or B12 and folate deficiency, for example, without needing to give a transfusion in a patient who's not symptomatic.
So that's red cells. So then if we move on to platelets for infants and children. So for most patients who are stable, who aren't bleeding, and we're therefore talking about a prophylactic platelet transfusion situation, a threshold of 10 is appropriate. So you would only transfuse if you're less than, if the plate count drops, then less than 10 times 10 to nine per liter. For patients with severe mucositis, sepsis, if they've got DIC, but they're not bleeding, you might want to keep a threshold above 20. Or if you've got, if you're inserting, for example, a non-tunnel central line, then you would, we'd want a threshold above 20. Thresholds for lumbar punctures, generally the guidance says a less than, 40. So you've got to have a platelet kind of 40 and above, but actually some units will have specific protocols and will accept a lower count. So again, like everything, look at what your unit policy said. For bleeding, moderate bleeding surgical procedures, unless it's minor, so for example, a tunneled central line, generally a threshold of 50. And then major bleeding or eye or intracranial, you're generally looking at 75 to a hundred. And usually we'll give 10-20mls/kilo. And again, once you get to a full platelet pack which is about 200 mils you will round, you'll just give a single platelet unit in that situation. So that's platelets.
FFP, so again, minor abnormalities of clotting without bleeding, without any other concerns, there's very little evidence, there is no evidence that giving FFP is going to correct those abnormalities. So for children who've got significant abnormalities of coagulation then we might think about using FFP or obviously in the major haemorrhage situation in combination with red cells. So we would give 15 to 20 mils per kilo. That's the dose of FFP.
And then in cryo, again, in children we're generally, these are patients who've got a fibrinogen of less than one. We use the cryoprecipitate as a source of fibrinogen. And we, we would give five to 10 mils per kilo. And sometimes in major bleeding, we will aim for a higher fibrinogen threshold as well. And some units will choose to use fibrinogen concentrate if you've got volume issues. Again, that's almost a whole other choice of product, but that just gives you some guidance about the sort of thresholds and volumes for the different products.
And just to summarize the sort of volumes of adult size products, just so you know, when you've got to full unit. So for red cells, it's about 250 mils for platelets, approximately 200 mils, for plasma, again, about 200 mils and for cryoprecipitate, a kind of full pooled unit is about 250 ml. So just to give you a guidance, but what you'll generally find is your possible transfusion lab will be really good at helping you not to prescribe, for example, one adult red cell unit plus 10 ml from a new unit, because that's obviously not a good idea.
SA: Yeah, if in doubt, give them a ring. They're always a fantastic resource, no matter where you are.
So are there any specific situations when a patient's thrombocytopenic that you wouldn't give platelets?
AK: That's a really excellent question. So, I guess there's two that immediately come to mind. So, first of which obviously is ITP or immune thrombocytopenic purpura. So, actually, generally we wouldn't give a platelet transfusion unless there was life threatening bleeding. Generally for ITP, actually, if the patient hasn't got at least moderate mucocutaneous bleeding, we would not do be doing anything. And if we did need to do something in a non kind of severe bleeding, life threatening bleeding situation, we would be using either intravenous immunoglobulin or steroids to try and bring the platelet count up. And the reason for not giving a plate transfusion is that they would just very rapidly be removed from the circulation because of the immune mediated destruction of platelets. In severe bleeding, you give a lot of platelets along with steroids and immunoglobulin as well. And so that's ITP.
The other time when platelet transfusion is contraindicated is in TTP or thrombotic thrombocytopenic purpura. And the reason for that, so this is a rare, very rare disorder in children either congenital or acquired. And essentially if you give platelets in that situation because it's to do with microvascular thrombi and the lack of this enzyme, ADAMTS13, you end up, you're almost by giving a platelet transfusion, you're potentially adding fuel to the fire and potentially giving more ability for, for these little microvascular thrombi to form. That's the other, the other reason when you might not, but I would expect in that situation, you guys will be speaking to your local friendly haematologist.
SA: Yes. I think that leads us really nicely onto talking about some kind of special situations within patient blood management. Can we talk a little bit about special requirements? So I know this particularly comes up in kids who are under HaemOnc who need very specific requirements to their, their blood products.
AK: Exactly. So, as you say, there are a number of special requirements which your patients might have in terms of the blood product. So if we just go through them you know, a little bit. So, first of all some patients may need CMV selected products. So the number of patients who need that is now relatively small. So generally we're talking about sort of neonates and we're talking about some patients, generally, patients post stem cell transplant no longer need CMV negative components. You, you will find that some units that still require that. So again, I think CMV negative components is another situation when you need to, to look at your local unit policies. I would, what I would expect for stem cell transplant patients is that there will be a clear communication from the place where the chance of a stem cell transplant to the shared care centre. And that, your transfusion laboratory in your local hospital should also have been informed of the patient special requirements. So you should know about that.
The other thing around stem cell transplantation obviously is irradiated blood products. Now, the reason for irradiated blood products is to remove the risk of something called transfusion associated graft versus host disease, which is a very rare complication of transfusion, and in fact, even rarer since we started leukodepleting, so getting rid of all the white cells from blood products, so now blood products are all leukodepleted at source, so actually the risk of that has reduced significantly, but it's not gone. Well, we don't feel the risk is sufficiently gone for all patient groups. So we're still looking at irradiating for stem cell transplant patients. So basically these are patients who are having allogenic transplants, also autologous transplants as well. And I think this is where you need to liaise with your local stem cell centre to know exactly at what point or if you can take the requirement for radiation off. So you, they should communicate that with you. New patient group the CAR T patients as well. So that's the kind of HaemOnc patients.
Then we also have certain drugs, again, that HaemOnc patients might have, so something called purine analogues, so fludarabine, Campath things like that. You'll also notice that all patients have HLA matched platelets, for example, they're always irradiated, and that's because if you're matching for HLA, you've got similarity between donor and recipient, and therefore, potentially, any white cells could survive in the recipient circulation and cause this, this graft versus host disease.
Then other immune patients, so patients with severe congenital immunodeficiency, neonates post intrauterine transfusion, little babies who are actually having an intrauterine transfusion also need irradiated products as well. Patients who've had ATG with aplastic anaemia. Patients who've had Hodgkin's Lymphomas, the requirement for lifelong irradiated products.
So that's the main categories, but again, look at your local transfusion guideline, which will summarize them. If you're not sure then speak to your transfusion laboratory.
So some patients might need more special blood or blood products. So patients with haemoglobinopathies who are on transfusion programs need blood that's more extensively matched for them. So all patients with thalassemia who are on a transfusion program or sickle cell, or patients with other transfusion dependent anaemias, need red cells that are, we call them extended phenotypes. So they're basically, are not just matched for ABO and RHD. They're matched, there's lots of other antigens on red cells and they're matched for those as well.
So those are the main special requirements that I can think of. And I think the key messages to speak to your transfusion lab.
The other thing I will say is that we used to recommend irradiation for all patients with DiGeorge syndrome, but the guidance changed for that in 2021. And now management of DiGeorge patients recommends that essentially under two, they have an assessment of immune function. And if their immune function is reasonable, this is in terms of their T lymphocyte count and the percentage of naive T cells. So they have to have more than 400 T lymphocyte count and more than 30% have to be naive T's. And if they have that under the age of two, then you don't need to irradiate. And over two, if they've not had recurrent infections, you don't need to radiate. So you might come across that change through your transfusion laboratories as well.
SA: So if in doubt, speak to your transfusion lab, speak to your friendly local haematologist, always check local guidance and be aware that the guidance is changing. So we're currently recording this in July 2024. But be aware that the guidance is possibly going to change in the coming months.
AK: Yeah, that's quite right. Yeah.
SA: Fantastic.
That's the end of. Part one. Join us next week for part two.
Thank you for listening to this episode of Master the MRCPCH. We would love to get your feedback on the podcast and any ideas you may have for future episodes. You can find link to the feedback page in the episode description, or email us at
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