New Blood for Old Problems

At work I get to spend quite a lot of time doing things to preserve life. Which is a pity for the plants in the garden. I must use up all my life-supporting skills in the hospital or next to the road. In the backyard I am a merchant of death and destruction. Or perhaps ritually offering up the souls of formerly green living things twice a year could be my own pagan religious practice.

No, there is not much hope of self-sufficiency for my family. Unless of course we can do more production of things you might need to eat in labs. Which can’t be that far off seeing as you can now eat hamburgers grown in a dish. Or produce organs on chips (no, not actual organs on the eating type of chips, more like this for research purposes). It’s sort of astonishing what we can produce in labs.

Even blood.

 

Replacing true blood with truly new blood

There’s more to this than finding a more convenient drinking supply for people who actually like to party like vampires (yes, that is a real thing and no, I am not going to link you there). And really, it’s bits of blood they’re talking about.

For medical purposes, all sorts of people need medical staff to give them a top-up of stuff that’s usually swimming around in your blood. In the operating theatre that’s mostly because these pesky individuals we’ll call “surgeons” keep on picking up sharp blades to “help” the patients. Because nothing heals like steel, don’t you know?

They do sometimes have to be cruel to be kind which means bleeding happens and your blood actually contains many useful thing, be it in the 5 or more litres in your “average” adult or the coffee cup’s worth in your newborn.

Blood contains quite a lot of fluid (quite useful), many proteins with many jobs (like the ones that take part in making blood clots that stop that bleeding) and lots of cells (things related to the immune system, fragments that also make clotting start and things like that). Most pertinently it contains the little flexible frisbees that do quite a lot of the colour work – red blood cells. It’s those red blood cells that carry lots of the haemoglobin that binds oxygen to get it around your body because cells are quite keen on using that oxygen to get things done.

When you bleed you lose those red blood cells as part of the deal and if you lose large amounts you can’t carry enough oxygen around and that comes with problems. Like cells dying.

So it seems obvious you’d like to give back something that could carry that oxygen. News that the NHS plans to trial lab-developed blood substitutes to carry oxygen around by 2017, apart from being another step along the way in some quite cool research, could be an announcement that heralds a big change in the way we do that replacement and be seriously big news for transfusion medicine.

 

Why bother when they’ll give people cake and drinks to give it up?

Well all the potential things that can potentially be an issue with giving blood from donations would take quite a while to go through. But here’s some obvious reasons.

The first is, good blood is rare. I don’t mean in a weird elitist sense I just mean it’s really hard work to get enough blood to supply the needs of the health system. The Australian Red Cross Blood Service say on their website that they need about 27000 donations each week to have enough available (they collected 1.32 million donations in 2013). That’s a lot of biscuits to hand out.

Then once you collect it you have to process it and store it and use it within a set period of time before you have to throw it in the bin. That’s even assuming you’re getting donors with the right stuff for the people who need the blood (which can be incredibly hard for patients with rare blood types).

The need for transfusion isn’t going down either. While I made reference to surgery, blood products are more often than not needed for people with chronic diseases or cancers. We’re a fair way off finding cures for every cancer that might cause people problems.

So rising needs and falling donation rates are a significant threat to supply. You can see how lab-based oxygen-carrying fluids have immediate appeal.

Novel approaches like enlisting the Vampire Finch are unlikely to work too [via galapagosconservation.co.uk]

Novel approaches like enlisting the Vampire Finch are unlikely to work too [via galapagosconservation.co.uk]

There’s also the numerically small but ethically soul-destroying issues of transfusion refusal amongst particular groups (especially Jehovah’s Witnesses). That would require a post all out there on its own.

But the other really big problem is that you don’t get to top up the red stuff without having some complications. There’s just no giveaways in medicine it seems.

 

Buy Now Pay Later

Earlier in my medical days my understanding was rudimentary – adding red cells didn’t help until you were really quite lacking and there were some impacts on the immune system but you could stop patients dying or having strokes or heart attacks. The internal dialogue went as far as “well, there might be some small risks but if it’ll prevent horror …”

There’s more known (and certainly more known by me) now. Transfusion (the giving the blood products bit) causes changes to the responses of the immune system (given the catchy acronym TRIM for Transfusion-Related ImmunoModulation). This is hugely complex and results in lots of observed changes.

It can stimulate immune activation causing various annoying syndromes and damage to organs. It can also reduce the immune response which can lead to higher rates of infections (particularly after operations) and for colorectal cancer it seems there is a relationship between the amount of blood transfused and the likelihood of cancer recurrence. It’s now well established that there is an association between receiving blood transfusions and higher mortality rates after heart surgery and certainly higher infection rates (in a dose-related manner) in heart surgery and other forms of operations. So it’s not something you choose lightly because the acute saving life benefit has to be weighed up against the long-term risk associations.

This knowledge has led to lots of work on how to reduce the need for transfusions. Those attempts have had a lot of success.  Recent National Blood Authority guidelines are a good example of comprehensive guidance to reduce transfusions. Efforts in Fremantle incorporated staff education, screening surgical patients for anaemia and treating as necessary, a new focus on stopping bleeding during surgery, reducing the number of blood tests and only using one bag of blood at a time. They decreased their use of red cells by 26% over 3 years, even as admissions to the hospital went up by 22%.

But this still won’t be enough in the long run and it doesn’t entirely solve the issue of scrambling the immune response.

Which is exactly why cold room blood mimicry could be really exciting. (I’ll be honest, I don’t actually know if the lab rooms are cold but I think blood and I think fridges – it’s not you, it’s me.) It could be new technology to wipe out a whole suite of problems.

As long as it doesn’t cause entirely new problems of course. Unknown things could still emerge. If it works though we should hopefully have more patients surviving and enjoying petri dish beef patties and marveling at organ chips.

Of course there’s nothing in the press release on whether they’ve thought of producing particular flavours for those real-life vampires. They might be the forgotten victims.

 

Notes:

I used a few sources for this post.

Some of it came from those National Blood Authority guidelines:

Patient Blood Management Guidelines: Module 2. Perioperative. National Blood Authority, 2012.

A lot of the stuff on TRIM also came from this paper:

Bernard AC, Davenport DL, Chang PK, Vaughan TB, Zwischenberger JB. Intraoperative Transfusion of 1 U to 2 U Packed Red Blood Cells Is Associated with Increased 30-Day Mortality, Surgical-Site Infection, Pneumonia, and Sepsis in General Surgery Patients. J Am Coll Surg. 2009; 208:931-7. 

And the results from the Fremantle group are in this paper:

Leahy F, Roberts H, Aqif Mukhtar S, Farmer S, Tovey J, Jewlachow V, Dixon T, Lau P, Ward M, Vodanovich M, Trentino K, Kruger PC, Gallagher T, Koay A, Hofmann A, Semmens JB, Towler S. A pragmatic approach to embedding patient blood management in a tertiary hospital. Transfusion 2014;54:1133-1145. 

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