Introduction – Blood Transfusion

00:01 Hello, in this lecture, I'd like to introduce the principles of blood transfusion.

00:07 We'll see that blood transfusion accomplishes the safe transfer of blood products from one person into another.

00:17 We'll see that there is strict criteria about who can donate blood and this is done in order to protect the donor and the recipient.

00:26 We'll also see how because of genetic differences between individuals, blood products need to be matched so that they're given to the right person.

00:37 We'll see that there are potential complications of blood transfusion but fortunately, these are really mostly very rare events these days.

00:47 Transmission infection has been a particular concern but that's now really very well controlled.

00:54 Now, transfusion involves the transfer of blood between individuals and it's really fascinating that blood really was the first tissue that was transferred between different individuals in many decades ago.

01:09 We tend to think of blood transfusion of transfusion of red cells, a pack of red cells, but there are many types of blood products that are now available and I'll address those during this lecture.

01:22 A key theme about blood transfusion is to decrease the potential risk of this procedure at all stages of the process.

01:30 Let's just think about the variety of blood products that are available.

01:35 I'm sure many of you are blood donors and when you give blood, you typically give around 400 to 440 mL's of blood into an anticoagulated bag, something similar to what is seen on the right.

01:50 Now, most blood these days is leukodepleted. What does that mean? Leukodeplete, white take out, take out the white cells.

01:59 The blood is essentially filtered to take out the white cells in the donation.

02:04 Why do we want to do that? Well, sometimes, white cells can provoke allergic reactions when they're given to a patient.

02:12 Also, there are some rare but important infectious diseases that are present within white cells and so taking out the white cells at this stage can reduce that risk.

02:25 Now, actually, when you give a blood donation, potentially, something like on the right, it's not given directly to a patient.

02:35 The blood is quite significantly processed into various fractions.

02:40 The blood is centrifuged after donation and the red cells at the bottom are concentrated in order to be used for a red cell transfusion.

02:52 The plasma can be taken off to make fresh frozen plasma and I'll talk about the uses of that later on.

03:01 Platelets are very important and they can be given to patients with thrombocytopenia.

03:08 Now, they're taken from the buffy coat, a layer of white cells and platelets that's visible after centrifugation.

03:16 So, you can already see how when you donate a unit of blood, how we can make very useful different fractions from that.

03:25 Now, here are some features of donating blood.

03:31 It's preferable if donors give their blood on a voluntary basis, so, they're not given payment.

03:39 So called altruism, why is that? Well, essentially, if people are being paid to give blood, there might just be a suggestion that they might perhaps lower the criteria for why they give blood.

03:53 People are more motivated if they're not being paid, And so, many countries do organize blood donation systems on this basis.

04:01 Of course, not everybody is allowed to give blood.

04:06 These so called exclusion criteria protect the donor so that the donor doesn't come to any harm by giving one bag of blood but also protect the patient.

04:18 Age is one. You mustn't be too young or too old.

04:22 And of course, if the patient, the donor is anemic, they mustn't give blood.

04:27 But in order to protect the patient, there are additional factors.

04:32 There are many of these. For instance, if the donor has a chronic illness or a malignant disease.

04:38 If they've had things such as a recent tattoo or they have a history of a intravenous drug use.

04:45 That's about the risk of potential viral infections such as hepatitis C.

04:52 Minor things even if they've had a recent live vaccination, just so that that infection is not spread perhaps to the patient.

05:02 The risk is absolutely minimal but you can see already how strict the criteria are for blood donation.

05:09 Now, when blood is given by a donor, it is screened.

05:14 Obviously, infections such as hepatitis, HIV, and syphilis.

05:20 We must look for those within the blood donation. There's two main ways to do this.

05:26 The first is by looking for the presence of antibodies in that blood against these infectious agents and that'll show that the patient has had some infection for some time, at least weeks, and that gives time for the antibody to develop. But also, particularly with hepatitis and HIV, we can look for the antigen, the presence of the infectious agent, the virus itself by using PCR, polymerase chain reaction.

05:56 Why do we bother to do that? Why not simply do an antibody screen? Well, sometimes, if a patient has a recent infection, they haven't had time to develop an antibody and in this so called window period of a recent infection and a blood donation during that period, there is a chance that infection could be transmitted before an antibody is produced but if we screen for the antigen, then, we can get around this concern.

06:27 You'll see on the right there a list of the type of tests that are done on a unit of donated blood.

06:37 The ABO group and Rhesus group, I'll talk about both of those in detail in a second.

06:42 Red cell antibody screen and screening for the infections that I've just described.

06:49 Let me introduce a major concept in blood transfusion, very important clinical idea and that is, of course, there are genetic differences between all individuals and that means that when we give a blood product from one person to another, we've got to cross match it to make sure that we are giving a safe unit of blood.

07:13 So, genetic differences between individuals mean that proteins on blood cells can be slightly different between the donor and the recipient.

07:23 You're not surprised by that. We all have 30,000 genes.

07:26 There are lots of allelic changes in those genes.

07:30 And so, sometimes, proteins on white cells and red cells are slightly different.

07:35 Now, that doesn't really matter except when the immune system becomes involved because these differences can be recognized by the immune system and lead to the production of antibodies against that protein and it's these antibodies that can cause the problems.

07:55 Now, as I also discussed when we talk about ABO in detail, remarkably, sometimes, we have these antibodies in our body against other people's red cells even when we've not even been stimulated or immunized by those red cells.

08:13 These so called natural antibodies just happened to be there.

08:16 We don't really understand why.

08:19 The classic example is the ABO system and because of this, when we give a blood product, we must test that the blood that's given does not react with antibodies in the patient and that's shown in the cartoon. Let me take that, take you through that in a little more detail.

08:42 So, here we are. Starting on the left, those red cells there of the donated red cells that we want to give to the patient but it may be that the patient has antibodies against those red cells and you can see the antibodies around those red cells.

09:01 So, we can put them together, the donor red cells and the patient serum and give them chance to mix.

09:08 And then, as you'll see in the middle, we can wash off the patient's serum so that we're left with the donor red cells and you'll see that in this case, some of the antibodies from the patient have indeed stuck to those donor red cells and that's a potential problem.

09:27 Now, actually, you can see how do we detect these? The red cells are just still individually floating around.

09:36 How would we detect that those antibodies are present? Well, cleverly, we can use something called the Coombs reagent on the right.

09:45 This is an antibody that's made in another animal perhaps like a sheep.

09:51 It's an anti-human immunoglobulin and if you'll see on the top right of there, this antibody is now crosslinking these different red cells through that antibody.

10:05 It's two layers of so called sandwich assay of antibodies.

10:09 And this Coombs test leads to the agglutination of the red cells.

10:14 They clump together and they visibly show us that those antibodies are coating the donor red cells.

10:21 That's a positive crossmatch. That can't be given.

10:24 Now, the other situation in which antibodies can be important is that they develop after a blood transfusion is being given.

10:32 This is perhaps less of a concern. It doesn't cause immediate clinical problems but problems that are seen a little bit later on.

10:43 Most important example of this is the Rhesus system and I'll explain the Rhesus antigen and the proteins decoded from that in some detail.

10:54 Now, why have I shown you that blood film on the right? Well, that's actually from a newborn baby and you'll see that there are a lot very primitive red cell precursors, so called erythroblasts in the blood.

11:08 That's unusual. You wouldn't normally see those certainly in an adult.

11:13 You occasionally see a few in a newborn baby but here, there's a lot.

11:17 The reason that this baby has been damaged due to hemolytic disease of the newborn.

11:23 The mother has made antibodies to the Rhesus antigen and they've crossed into the placenta.

11:30 And so, that mismatch between the mother and the baby is one example of what can happen when an antibody is made between different individuals.

11:40 I'll show you more about the clinical importance of the Rhesus antigen in subsequent slides.