Why Do We…Leukoreduce Blood Products?
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Why Do We…Leukoreduce Blood Products?


Hi, this is Joe Chaffin, and this is
another Blood Bank Guy Podlet. Today, we’re going to do a 10 minute tutorial
on why we leukocyte-reduce blood products. The truth is that things
have changed a lot in the last 10 to 15 years. In fact, for most of us in the
United States and Europe, this is really not a conscious decision. We live in an
age of (in the United States) “unofficial” universal leukocyte reduction, whereas in
Europe it is official that things are universally leukocyte reduced. But the
vast majority of cellular blood products such as those that you see at the bottom:
Whole blood, red cells, and both types of platelets are leukocyte-reduced.
“Leukocyte reduction” simply means removing the majority of the white cells
from transfused blood products; getting those suckers out of there! A multitude
of reasons why we do this, but first, let’s describe why we NEED to do it! There’s actually a lot of white cells that go along in these cellular blood products, and they’re just along for the ride! They don’t have any specific benefits Let’s look at red cells: A unit of red cells h as on average
somewhere around two point four trillion red cells, which is obviously a lot, but
in addition there’s about a BILLION white cells that go along with that, or
10^9 white cells. Same thing with platelets (on the bottom), a unit of apheresis derived platelets has, by definition, at least 3×10^11 or 300 billion platelets, but in addition, they have somewhere in the range of a hundred million or more white cells! Again, a lot of white cells. They don’t have any great effects, but we know that they can potentially have some negative effects, and let’s talk about those Certainly we know that they have immunologic effects. They degenerate, they die off, they undergo necrosis and apoptosis as they sit in bags of blood
waiting to be transfused and as they die they secrete substances into plasma
various toxic substances certainly but also a bunch of cytokines and those
cytokines we are very familiar with as causing febrile transfusion reactions
especially in platelet transfusions and there’s debate and discussion and
research into some of the other potential adverse effects that can
happen also we should know that those transfused white cells are responsible
for presenting foreign HLA antigens to the host immune system. And this is an
odd, kind of counterintuitive thing. I’ll show it show it to you in just a second
but the bottom line is that that leads to
anti HLA antibody formation. When a person forms anti HLA
antibodies they can have problems with future platelet transfusions, become
refractory, they can have febrile transfusion reactions when they’re
transfused HLA incompatible blood products, and down the
line they can have issues if they are going to undergo a stem cell or a solid
organ transplant as a result of those HLA antibodies. Again here’s how this
works: so we’ve got some platelets they’re
going to be transfused. Platelets carry HLA I and platelet specific antigens,
whereas the white cells that go along with them carry not only HLA class I
antigens but also HLA class II. The class II are the big deal because it
looks like those transfused HLA class II antigens on the transfused
white cells are responsible for presenting those HLA class 1 antigens
and platelet specific antigens to the recipients so that you end up with the
formation of anti HLA class I antibodies or anti-platelet antibodies. The reason we know this is if you take the same
situation you take away the white cells in other words if you leukocyte reduce
and that interaction with the host system does not lead to the formation of
those antibodies. So it seems like the transfused white cells are
responsible. In addition, the other immunologic effect that we’ve
discussed in the past is transfusion- related immunomodulation or “TRIM,” a big
deal in the discussions in the late 1990s when we were talking in the United
States about going to universal leukocyte reduction. We know that there’s
some evidence of increased risk of post-surgical infections and tumor
recurrence as well as reactivation of viral diseases and potential for
increased short-term mortality after transfusion. That we know, but what we
don’t know is what causes it. It was postulated that leukocytes were
the cause but studies that have been done since essential universal leukocyte
reduction haven’t shown a clear decrease in the in the TRIM-related effects. We’ve talked before about the attack on host HLA antigens and transfusion associated
graft-versus-host disease, that’s in a separate podlet on irradiation. I’ll
leave that alone for now. Finally, there are infectious risks from transfused
white cells. Some viruses such as CMV and EBV and HTLV live in white
cells, so as a result can potentially transmit infection. And the prion
discussion was primarily discussed in in Europe, with
the the possibility of variant CJD being decreased or Creutzfeldt-Jakob disease
being decreased by universal leukocyte reduction. It probably doesn’t happen at
least not completely. So here’s transfusion-transmitted CMV.
Notice that the “C” for CMV is only in one of those white cells. That simply
means that not all of the white cells carry CMV, in fact a minority of them
carry CMV, but the one one or ones that do can go into a immunocompromised
recipient and cause transfusion transmitted CMV. Well, how do we get rid
of these white cells? There are two ways: Filters, or processes built into
apheresis machines, and let’s talk first about the filters. Leukocyte reduction
filters, you see a picture of one up on the the top left of the screen they work
in a couple of ways and this is somewhat conjecture because the filter
manufacturers are a little tight-lipped on this but this is probably at least
mostly true. The flow of blood goes along this way and basically they first act as a barrier just like you would expect for a filter. They have
a pore size that allows red cells to cruise through but does not allow white
cells to cruise through especially at cooler temperatures when white cells are
less deformable. But in addition, it’s not just a barrier but it’s also an
attractant. This filter is built, the material is built to attract white cells
either through charge or some other physical factors so the white cells get
stuck against the filter and that may cause even more of an
effect than just the barrier method. it’s It’s more complicated than this. This picture
from an article by Gordon and Gudino in in Transfusion in 2001 really
illustrates that with a scanning electron micrograph. I do want to show
you though, graphically, how efficient filtration is. Imagine if you have a
thousand white cells, and this actually IS, (if you want to pause it and count!).
It is a thousand white cells on our slide. If we leukocyte-reduce using
current methods what we’d see is that there those methods are at least 99.9
percent efficient so we would only have one white cell left out of a thousand
and in some cases one out of 10,000 it’s a it’s a very very efficient method of
leukocyte reduction. Now, when we look at apheresis machines such as the Amicus or
Trima that you see here they separate blood based on specific
gravity like you see in here and so they can target the specific product but in
addition for example the Trima has a leukocyte reduction system that you see
at the arrow here which specifically eliminates leukocytes to an even greater
extent and basically makes them as leukocyte reduced as filters do. So,
what do we end up with well there there’s two numbers that you should be
aware of. In the United States, a leukocyte reduced unit of blood has less
than 5 x10^6 or 5 million residual white cells by definition in
95%. That number in Europe is less than 1 million. But you should know that 99% or
more of the products in the United States actually do meet the European
standard we just don’t say that. When does it happen? Well, pre storage is
probably best. It’s not really completely pre storage, it’s either at
the time of collection or within 72 hours of the collection basically before
the product has a chance to be stored for a long period of time.
Pre-transfusion leukocyte reduction is less optimal. It’s done in the
transfusion service or at the bedside, thankfully not very often at
the bedside! Well we’ve kind of built the background let’s talk now about the
indications. There’s universal agreement that leukocyte reduction decreases the
risk of febrile reaction in a history of a patient with febrile transfusion
reactions and that’s because of the removal of the white cells, getting rid
of this before the cytokines can be secreted, as well as decreasing HLA
immunization and that’s the second one that HLA immunization prevention in
platelet recipients with hematologic malignancies that leukocyte reduction
works for, and CMV transmission prevention in susceptible recipients.
There’s debate about that last one whether it’s as efficient as using
purely CMV seronegative products but that is a topic for another podlet, that
is for sure! The other one that that’s recently well
agreed on is that the prevention of reperfusion injury in cardiac surgery
patients but that’s still becoming known but there is good evidence for that. There’s also partial agreement on HLA
immunization prevention in patients with non hematologic malignancy. I talked
about the TRIM effect prevention before. Some people say that using leukocyte
reduction can decrease septic transfusion reactions
because there may be some decrease in the amount of things like Yersinia, and
TA-GVHD there may be some reduction just like post transfusion purpura but it’s
not sufficient by itself. A couple of details that you should know: There’s a lot of cost to this. Leukocyte reduction is costly and the
utility may be limited. The studies don’t really prove a whole lot of cost savings,
and there’s some rare complications that you see listed there especially the ACE
inhibitor patients that get hypotension but not much more to say about that.
Remember for TA-GVHD you have to irradiate the white cells to completely prevent
it. It may decrease TA-GVHD by leukocyte reduction but it does not
completely eliminate it. Finally, granulocytes can be irradiated
but cannot be leukocyte reduced I hope that’s obvious. Filter failures happen,
most commonly in donors with sickle cell trait, and I mentioned before that cold
red cells filter much better than room-temperature red cells due to the
decreased flexibility of white cells at those temperatures. Okay that’s it for
this ten minute tutorial I hope it’s been useful for you! Thanks and have a
great day!

About Ralph Robinson

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7 thoughts on “Why Do We…Leukoreduce Blood Products?

  1. Hi,
    I just stumbled on this video and then your blog and web. Great great stuff.
    Thanks so much for doing this. I know I will spend many hours learning from you.
    Garrey

  2. I think I may have missed it, but it was mentioned that granulocytes can be irradiated but cannot be reduced, why is that?

  3. you mentioned the cooler temp may not allow white cell to be "formable" to squeeze through filters…does it make a difference if you use a blood warmer?

  4. Dr Joe– Are the daily meds I take for high blood pressure and cholesterol passed on to and have an effect on the recipient of my donated blood or are these meds also filtered out in processing? Thanks.

  5. I really learn a lot. Hope you would share the steps of preparation and collection of all blood components and its clinical use. Thank you!

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