
Which IV Iron Formulation Is Right for Your Patient?
Matthew F. Watto, MD: Welcome back to The Curbsiders . I'm Dr Matthew Frank Watto here with my great friend and America's primary care physician, Dr Paul Nelson Williams. Paul, are you a fan of iron?
Paul N. Williams, MD: You know it! That's why we've done about 12 episodes on iron at this point.
Watto: As in, pumping iron?
Williams: Sure, look at me — I'm jacked!
Watto: Paul, we had a great guest on this episode, Dr Tom DeLoughery (@Bloodman). He was a great guest and a hilarious guy. Let's talk about it, Paul: microcytic anemia. I know iron deficiency can cause that, but what else can cause microcytic anemia?
Williams: I appreciated the breakdown of this episode. Our guest says that there are four big things that can cause microcytic anemia that you need to know about. One is iron deficiency; that is far and away probably the most common one. Then there is anemia of chronic disease, which I don't think we think about as much. If the mean corpuscular volume (MCV) is less than 70 fL, it's probably not anemia of chronic disease, but anemia of chronic disease can cause microcytic anemia. The next is thalassemia, which is probably more common than we give it credit for. The last one is sideroblastic anemia, which is something you're probably not going to be diagnosing in adulthood and is an uncommon cause.
So really, if you consider those first three causes — especially with the framework that he gives — it can be pretty easy to distinguish between iron deficiency, anemia of chronic disease, and thalassemia. That's what you need to figure out before we start just giving iron willy-nilly.
Watto: I don't think I've ever even seen sideroblastic anemia in a chart outside of an exam setting. I feel like you're more likely to see consumption written in the chart than sideroblastic anemia!
Williams: Yeah, I feel like it's the type of disorder I would've been quizzed about during floors a million years ago but not something I've actually seen — ever, I don't think.
Watto: Now, Paul, when I'm working up anemia, I like to look at all the things: red cell distribution width (RDW), total iron binding capacity (TIBC), iron. Is that a waste of my time, Paul?
Williams: I would never call it a waste of your time. I'm sure it's of academic interest, but both our guest and I, in my own practice, don't spend too much time dwelling on those when we're chasing down microcytic anemia. Dr DeLoughery does not look at the TIBC all that often. It really is the ferritin, the MCV, and the hemoglobin that are the big-ticket items when you're working up iron deficiency anemia. The rest is all largely window dressing, according to him. I feel good about that, because I don't like sweating out equations and working through those things.
Watto: Okay, so we're looking for low hemoglobin. An MCV of less than 80 fL or so is usually considered microcytic in most labs. Now, the ferritin cutoff was an interesting one. Some labs might say 15 ug/dL or less. Some labs say 30 ug/dL or less. Dr DeLoughery recommends a ferritin cutoff of 30 ug/dL or less. But for most patients, we're usually going to treat to at least a ferritin of 50 ug/dL, because if patients are fatigued from iron efficiency, they usually feel better once we achieve a ferritin level of 50 ug/dL or higher.
But we should remember that the reason why the lab cutoffs are lower is because they're looking at population average. And because iron deficiency anemia is so common and a large portion of our population has iron deficiency, the average ferritin values are lower than what ideal, healthy levels should be. If you just measured ferritin among patients with normal iron stores, the ferritin cutoff would be much higher.
Paul, what do you think about these specific ferritin cutoffs that he recommended? Have you heard about that before? Because when I was prepping for this, I was unfamiliar with those cutoff values and what values we should consider when determining treatment.
Williams: Do you mean in terms of when symptoms actually occur?
Watto: Yes. For example, he said that for patients experiencing fatigue, you want to get the ferritin to 50 ug/dL or higher. And then he mentioned two other symptoms: restless legs and hair loss.
Williams: Yeah, and for restless legs, you need to get ferritin above 75 ug/dL to actually achieve adequate iron levels in the brain. And then for hair loss, your goal is to get to at least 100 ug/dL to reverse the hair loss, if iron deficiency is indeed the contributing cause and not just getting old.
Watto: For a lot of patients, they might need IV iron to get their levels up that much. Dr DeLoughery checks levels every 3 months or so, for the most part, because you want to give it some time to re-equilibrate after you give the iron.
Now, Paul, when I'm trying to get those ferritin levels up, I usually tell my patients to take their iron with coffee and tea. Is that a bad thing to do?
Williams: Bad news for us, Matt, and for the rest of the world. But yes, unfortunately coffee and tea can reduce your absorption of iron, so you should probably avoid drinking either of those within an hour of taking your oral iron supplementation. If you want to boost absorption, you can take your supplement with meat protein. So, substitute steak instead of your coffee, I guess?
There's also always an ongoing debate and discussion about vitamin C potentially increasing iron absorption. Our guest, Dr DeLoughery, is a fan of it, but I think the jury is still largely out as far as that goes.
Watto: And it seems like coffee and tea really impact iron absorption. I think he said it's like 80% or 90% decreased absorption; it was very significant.
Williams: I know we have a long history of championing coffee in terms of being good for everything, but this might be the one instance where you don't necessarily have to avoid it; you just have to delay it.
Watto: Yeah, exactly. Just make sure to avoid taking your iron within an hour (on either side) of coffee consumption and you're good to go.
Williams: That would still be a real problem for me.
Watto: When you have a continuous IV of coffee, that doesn't give you much time to get the iron in, Paul!
Williams: Yep, and speaking of IVs…
Watto: I just wanted to quickly shout out some IV iron formulations. The ones that I've had more experience with are IV iron sucrose and ferric gluconate. The reason I'm most familiar with those are because they are the cheaper formulations and they happen to have been on formulary. However, those are not the best formulations if you have the options, because the newer formulations can be given quicker and in a single dose or two doses compared to the ones I just mentioned, which need 4-8 weeks of weekly IV doses to administer the amount we'd like.
Dr DeLoughery liked low-molecular-weight iron dextran because it comes in 1000 mg and you can give it within an hour. This is the formulation we discussed with Dr Auerbach back in 2018. Dr Auerbach told us that when you give low-molecular-weight iron dextran to your classic anemia patient — let's say a young woman with iron deficiency who has a hemoglobin of 7 g/dL — they'll start to feel better before the iron is even done infusing! It's pretty well proven.
Williams: Yeah, patients will experience a reduction in ice craving as they're receiving the treatment, which is wild.
Watto: Paul, why would it be a bad idea if I gave someone ferumoxytol — which comes in a dose of 510 mg and you have to give it twice — before I was going to, say, send them for an MRI?
Williams: In that specific circumstance, it's important to know that ferumoxytol can impact MRIs because it acts like contrast. And that effect can persist for 3 months after the infusion itself, so you can significantly alter the results of your MRI and make the imaging hard to interpret if you don't space those things out. That would be one reason to avoid ferumoxytol, if you're planning on upcoming imaging.
Watto: The other IV iron formulation that I was really excited to try out was ferric carboxymaltose. It comes in at 750 mg per dose, so you can give one or two doses depending on the severity of iron deficiency. But why might that be a bad idea?
Williams: It's nice of you to ask. So, there's the possibility of symptomatic hypophosphatemia with ferric carboxymaltose, which, again, is wild. It's always a delightful surprise to discover the terrible things you could potentially do — even though they are, by and large, safe.
Watto: The hypophosphatemia sounds bad because it sounds like if you try to give the patient phosphate, it gets worse because the body just accelerates how quickly it's getting rid of phosphorus. It's bad, Paul. So, I will not be giving that one. Ever.
Williams: Yeah, I don't think I've ever ordered that one happily. I would probably avoid it if I had better options available.
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