Back when I was at the University of Northern Iowa, my friend Chad Baumler decided that we could pay for our fraternity’s formal if everybody donated plasma twice and threw the money into a fund. It sort of worked…about half the guys (including myself) rolled up our sleeves and donated plasma and we all went up to Minneapolis and had a good time for less money than we otherwise would have were it not for Chad’s fearless leadership. I suppose everybody who’s been a little hard up for cash has donated plasma one time or another.
(It occurs to me that perhaps I shouldn’t have mentioned these details as I’m sure I just implicated us in something that would have gotten us in trouble, but it was 21 years ago and I feel like the statute of limitations is up on this).
Well, another day, another miracle cure. First hydroxychloroquine, then oleander extract (that’s a hard NO people) and now convalescent plasma. The difference is, we might actually be on to something with convalescent plasma (CP).
What is convalescent plasma?
Let me say up front that convalescent plasma actually does appear to be worth something, and this is a very good thing. Now, when I say “worth something,” that comes with several very important qualifiers, so don’t go down to your local bar just yet and celebrate. Let’s talk about CP and why the decision to authorize emergency use comes with several problems.
Firstly, what is convalescent plasma? Well, you remember that whole antibody discussion – you need them to tag viruses or bacteria or whatever to be marked for destruction? Basically, when somebody is recovering from COVID-19 (it would appear they need to be symptomatic, so merely being SARS-CoV-2 positive isn’t enough), their immune systems have made a bunch of antibodies. In theory and—to a certain extent—in practice, you can take somebody else’s antibodies and improve your immune response to the infection. Kind of like an antibody transfusion. The way you do this is by a plasma donation.
Plasma, if you don’t know, is basically the liquid part of your blood, minus the red blood cells (that’s not exactly correct, but don’t worry too much about that). You can donate blood, the blood is spun down, the red blood cells are spun out (because they’re heavier) and then the plasma is left over. What it also includes is antibodies and some other stuff but in the context of this discussion, we care about the antibodies.
And again, this appears to be working in certain (BUT NOT ALL) COVID-19 patients…and that parenthetical back there is a really big deal. Don’t be thinking for one second that convalescent plasma is a silver bullet that’s going to bring down this werewolf every time. It won’t. If you get sick, CP might help you. But it might not. And I’ve been following the cases of several physicians treating COVID-19 patients who’ve given CP and have ultimately had to turn off the ventilator.
But…sometimes it appears to work. YAY! We’re in the clear, right?
No…we’re not in the clear until you get one of those dope mRNA vaccines scientist are working on that I mentioned in another post.
Is convalescent plasma a cure for COVID-19?
Recently, President Trump announced emergency authorization of the use of convalescent plasma in COVID-19 patients. People on one side of the political spectrum rejoiced in this removal of red tape, people on the other decried the move as undermining the scientific process. I will (probably unsuccessfully) attempt to stay out of any political commentary here. An explanation, though, as to why this decision comes with complications is in order.
Like anything else, convalescent plasma comes with risks. CP is essentially fresh frozen plasma (FFP), which has been used in developed countries for quite some time for a variety of different things. You remember when I told you five paragraphs ago that “what it also includes is antibodies and some other stuff but in the context of this discussion we care about the antibodies.”
Well, I lied. We very much care about the “other stuff.” The other stuff that’s in there also includes factors that help blood coagulate (form clots) and stop bleeding when you cut yourself. If your body didn’t do that, you’d just keep leaking until you died and that brings us to what we normally use FFP for…
Sometimes you don’t want your blood to clot. Sometimes your blood clots inappropriately and then bad things happen to you. Probably some of you know people on Warfarin/Coumadin. Maybe you even know somebody on Xaralto or Eliquis. All of these drugs are anticoagulants. They keep your blood FROM clotting so that you don’t throw a clot to your brain and have a stroke. If you have a history of deep vein thrombosis (DVT)—which is when a clot forms in the large veins in your legs—they prevent that from happening. You don’t want a DVT because the thrombus could dislodge, move into your lungs and kill you. Anticoagulants help prevent this. Nice, right?
Well, what happens if you take an anticoagulant and you get into a car accident and you’re internally bleeding? Your body can’t stop the bleeding because it can’t coagulate because of the medicine you’re on. It’s time to mention that “other stuff” in the plasma. The other stuff includes clotting factors. So, when somebody is bleeding internally, we administer fresh frozen plasma to take advantage of the clotting factors so that you can start clotting again and not bleed out internally.
But think about what that entails now. The other stuff in the convalescent plasma also includes those clotting factors. But many people who get COVID-19 and who get a dosage of CP aren’t on an anticoagulant. So, you just doubled up your clotting factors and now you might make clots inappropriately. And that turns into all sorts of bad things like strokes and blood clots that move to your lungs and kill you.
There’s also something called transfusion-related acute lung injury, or TRALI. TRALI is the leading cause of transfusion-related mortality and FFP is public enemy #1 when it comes to TRALI. TRALI isn’t actually a clotting problem and quite honestly, the causes of TRALI are…well…they’re really, really complicated. The short version is that the plasma donation causes cells in your lungs called neutrophils in tissue called your pulmonary endothelium to cause something called permeability edema.
This leads to something we call death 5-25% of the time.
Oh hey. You know how the virus was also doing wild damage to your lungs, right? Now add to that your own immune system doing damage…
There’s also something called transfusion-associated circulatory overload, which has been given the rather endearing name “TACO.” It’s similar to TRALI but the specifics behind all of this—trust me, you don’t care. Suffice it to say that the things that TRALI and TACO cause are hugely exacerbating to people already put in a bad way by COVID-19.
There’s also allergic and anaphylactic reactions and a few other more obscure risks but here’s the point: Convalescent plasma isn’t without a set of risks that, quite honestly, extends beyond that of hydroxychloroquine.
So should we be using convalescent plasma at all?
Authorizing emergency use of convalescent plasma complicates our ability to figure out what the right dose/treatment schedule should be. If everybody is getting it, we’ll have less ability to figure out in which patients it’s most effective, and which patients likely WON’T benefit from it. And this, subsequently, means we’ll have difficulty keeping people diagnosed with COVID-19 from the risks of using CP.
I completely understand the argument to just go ahead and give it, particularly if you’ve got a loved one on a ventilator. I totally get it. I also get the concern that it feels like CP might be held back from certain people in the name of science because we need research.
True enough, science doesn’t particularly care. Science isn’t always nice. Actually, science is never nice. Science is a cold, calculating process that—when it’s done right—benefits the human race in aggregate.
Will we save a few lives by authorizing emergency use of convalescent plasma? We might.
Will the emergency use authorization put lives at risk by not fully investigating the risks that come with use of convalescent plasma? Very much so. That’s the trade-off here. That’s why the decision to implement it was so complicated.
If you didn’t know, now you know.
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