Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is Narrator - ? 00:12 provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Speaker 1 00:31 Welcome to HelixTalk, Episode 149, I'm your co host, Dr. Kane, Dr. Khyati Patel 00:35 and I'm Dr. Patel, and the title of our episode today is replenishing the missing element. A complete review of iron deficiency anemia. In today's episode, we're going to cover overview, kind of a definition of what Ida iron deficiency anemia is, its diagnosis. What are all the lab values mean, and why do we draw them? What are the treatment options that are available, and how do we monitor a patient with Ida and Speaker 1 01:03 Dr. Patel? This was actually an episode suggestion from a listener. So for the listeners out there, if you have a topic that you want to hear more about, just go to helix, talk.com and contact us, and we'll add it to our list of potential topics moving forward. But we love getting feedback from the listeners, and this is one of those episodes that was suggested. Dr. Khyati Patel 01:23 All right, I think it does make sense for us to get started with a small case. So to set the stage, you know, TR is a 52 year old patient. This is very similar to a patient that I encountered in my clinic. Past medical history that's significant for osteoarthritis, history of multiparity and GERD comes to the PCP office, complains of fatigue, weakness and shortness of breath on exertion. That's going on for about a month. She's not felt like this before. She's been kind of having irregular menstrual cycles, and some of them have had heavy flow. She's not complained or seen any symptoms of GI bleed. You know, the PCP does the lab work and finds that her hemoglobin is 11.5 serum ferritin is 20. The T sat, which is the saturation of iron, it's 17% total iron binding capacity on the red blood cells is high at 450 and the serum iron, which is the pure iron concentration in the serum, it's 45 which is a little bit low. And she doesn't have any known drug allergies. And her medications. There is no regular chronic medication she's taking, but taking the Tylenol for her arthritis pain and PRN, use of antacids whenever she kind of feels that her GERD is flaring up. So thinking more about what her likely diagnosis is, and you know, if possible, what the treatment options that are there for? Speaker 1 02:54 TR, yeah, so in terms of anemia, and we'll define anemia in a second, but in terms of anemia, there's a couple different kinds of anemia, and we kind of group them into drug induced anemias, nutritional anemias, and then anemia of chronic disease. So in terms of drug induced anemias, this would be something like a plastic anemia, where we've damaged the actual bone marrow, the stem cells, the multipotent hematopoietic stem cells, where they don't produce any new red blood cells. Megaloblastic anemia, this is where there's some abnormality and megaloblast production in the bone marrow. And then also hemolytic anemia, this is where the body is destroying some of the red blood cells, and certain drugs can cause that, right? Dr. Khyati Patel 03:39 I think chemotherapy drugs comes to mind, especially when it comes to a plastic or mega plastic type anemia. A nutritional anemia is kind of like the umbrella of what we are talking about today, which includes nutrition deficiencies such as iron, vitamin B, 12 or folate. I would say half of the nutritional anemias are related to iron. So it does comprise of a fairly large amount of anemia that we see in practice. Speaker 1 04:06 Then the third kind is anemia of chronic disease. This is sometimes seen in chronic kidney disease and definitely seen in chronic inflammatory conditions like rheumatoid arthritis or psoriasis, and in chronic kidney disease. This is because the kidneys involved in making Erythropoietin, which is the stimulating hormone to tell the bone marrow to make more red blood cells. And these inflammatory conditions is kind of the body's natural response to that inflammation to increase stored iron, and the actual serum iron can actually be a little bit low, right? Dr. Khyati Patel 04:40 And therefore in some of these chronic conditions, we especially like CKD, we may see the use of Erythropoietin, stimulating agents that are used alongside the iron therapy. But our focus today is Ida, or iron type therapy. So before we even get into. So the diagnosis kind of it's important to understand what are kind of like, the etiology, or quote, unquote, risk factors for iron deficiency anemia. Normally, as we said, this is nutritional type of anemia, so any type of decrease intake or insufficient dietary intake of iron could lead to that certain patients have restrictive diets. Or maybe, maybe it's a, you know, self malnutrition. Maybe it's the lack of foods that are available for them to consume that provides iron. There's some notion Dr. Kane, especially, being a vegetarian coming coming from that dietary background that vegetarian people are always, you know, deficient in iron, and they should be taking iron supplement. And, you know, the myth is that that's not true. There are a lot of plant based products that do provide recommended amount of daily iron if there are no additional dietary restrictions on top of that, yeah, Speaker 1 05:58 and we'll actually go through some non pharmacologic therapy later, focusing on some dietary choices that don't necessarily involve meat that can provide some of that iron. So we'll definitely get to that. Another risk factor to think about, or etiology, is malabsorption. So this is someone with chronic gastritis, someone who had gastric bypass, maybe someone with Crohn's disease, where there's some alteration in the GI lining itself. So even if that patient is getting a good diet of iron in they may not absorb it very well because they have some disorder in the GI tract itself, right? Dr. Khyati Patel 06:31 Or maybe they're taking medications to help with this disorder, right? So if they have gastritis, they might be on a PPI that lowers the pH of the stomach, that impairs the absorption of the iron. Other states, such as increased requirements, such as pregnancy, could also lead to Ida. And then, last, but not the least, the obvious thing is, you lose blood, you lose RBCs, you lose iron. And so you talk about large blood volume loss such as trauma or motor vehicle accident, and maybe more, more of a chronic based abnormal menstrual bleeding or maybe postpartum blood loss. But even some of the small bleeds, if they're going on for a long period of time, such as gi bleeds, bleeding hemorrhoids, maybe it's a bleeding varices or even continued nose bleeds, they could eventually end up causing Ida, Speaker 1 07:27 no doctor Patel in terms of like signs and symptoms of anemia in general, for iron deficiency anemia, this is almost never an acute onset thing, meaning it's not like today you wake up and yesterday you were fined, and Today you lack iron. This typically happens over a longer period of time, but in someone who, let's say, already had a low hemoglobin and now has some acute bleed, for example, they may experience some of these acute symptoms like tachycardia, or they may just complain of palpitations, especially older individuals could complain of angina, if they have a supply versus demand problem with myocardial oxygen, they could be dizzy, light headed, they could actually have hypotension, especially if they lost a lot of blood. Again. These are not typical for iron deficiency, because that's usually for an acute blood loss problem. But Dr. Patel, what are some of the more chronic symptoms that someone with iron deficiency may see? Dr. Khyati Patel 08:20 Yes, absolutely right. So, yeah, iron deficiency doesn't happen overnight, so most patients come with these chronic symptoms such as shortness of breath, fatigue. Feel like they're we they're not able to do the chores and activities they were once able to do without any effort. They feel tired malaise. They may have some sensitivity to cold. They have pica, which is compulsive eating of ice. And then other pica behaviors are seen where they have more affinity to consume non‑food items. Some patients may complain of restless leg syndrome. And then, interestingly enough, there's some changes happening in the mouth, where they feel they're losing those papillae, which is that rough structure on the tongue. Tongue becomes smoother, and there is some dysfunction of the salivary gland production too, so people can have reduced salivary flow, feel a little bit more of a dry mouth. Maybe that's another reason why they chew on the ice, but it kind of goes together. And in addition to some of these changes in the mouth, some signs that we can appreciate is changes in the fingernails, where their nails are becoming more of a spoon shape, or we may see horizontal striations paler of the skin, so they may look a little bit pale, brittle nails are also some of the integratory changes that can happen. And then, obviously, if they have had GI bleed, small, minor, we could catch them into doing the occult blood test that might turn positive. And these are kind of like the telltale signs, and especially when we're looking at IDA in kids, we're looking at thriving. So if they're not gaining proper weight, nutritional deficiency, not just iron, it's usually on the top of the pediatrician's mind, and they may end up checking for IDA labs. Speaker 1 10:18 And then, in terms of, you know past medical history for patients, some of the some of the risk factors that might cue you in more to Ida or other anemias could be heavy menses or prior pregnancies. Patients with celiac disease, where they might not absorb iron as well, or any auto immune gastritis type problem, those with a known history of GI bleeding, or they donate blood a lot. Obviously, they're losing iron and blood, and then really just kind of another risk factor would be anyone who's on a blood thinner or an anti platelet therapy or any anticoagulant, NSAIDS, anything like that, they're just more prone to bleeding, especially occult GI bleeding that you may not notice, and that would, again, kind of cue you in a little bit more that you might go down this Ida pathway. Dr. Khyati Patel 11:04 And so keeping this history and signs of symptoms in mind is important to, you know, give more of a holistic pictures, but we kind of still need some laboratory values to confirm the diagnosis. And, you know, depending on the type of anemia, there is a whole laundry list of different lab tasks that you could be doing. But when it comes to specifically following the IDA algorithm, we look at in global terms iron studies and CBC with differentials; we're kind of going to break down each of the components and what they mean, and what are some of the normal and abnormal values. Yeah. Speaker 1 11:42 And really, for any kind of anemia, the definition of anemia is that you have a low hemoglobin. And it kind of depends on who you ask. But today we're going to say that in women, hemoglobin less than 12, or in men, a hemoglobin less than 13 is considered anemic. Doesn't mean you have iron deficiency, per se. We have to do other labs, but that's kind of a starting point for anemia in general, yeah, Dr. Khyati Patel 12:03 and I think it's important to mention, because there is some evidence that people may have iron deficiency but not have anemia, meaning their hemoglobin is still being compensated, and it's fine, but the true Ida, the iron deficiency anemia will also have the, you know, lowering of the hemoglobin. And then looking at the other components of CBC, we may find decreased or normal mean corpuscular volume, which is basically the volume of the red blood cells in early stages of Ida. We may find this to be very normal, but in a severe anemia, we may find this to be decreased, and that's why we call iron deficiency anemia, more of that microcytic anemia. Speaker 1 12:50 Yeah, we can also see a decrease in MCH C, this is the hemoglobin concentration in each red blood cell. And again, this is going to be low because you don't have a lot of iron to have the hemoglobin protein, which is part of that red blood cell so that MCHC will also be low in iron deficiency anemia. Dr. Khyati Patel 13:10 And in some cases, we may also see that the red blood cell production is impacted. So we may see low red blood cell counts, because obviously we need to have iron to make RBCs, and we may even see that the reticulocyte count has gone down. Reticulocytes are your immature RBCs again; they also need iron for the production and Speaker 1 13:37 then, not necessarily diagnostic of Ida. But it's not uncommon that we'll see platelet count being higher. And the thought here is it's some kind of like a reactive process in response to the anemia. It's not necessarily iron deficiency causing it, but it's the body's response to that iron deficiency anemia, right? Dr. Khyati Patel 13:55 So that's a global picture of what a person with IDA, you know, CBC values can look like. What we do, in addition to that, is to draw some iron studies. Now, the consensus on Iron studies is different. Some hospitals may our clinicians may just draw one lab that is a little bit more confirmatory versus throw made basically a set of labs. We call them iron study labs, that include some of these that we're going to talk about, but the first and foremost I'm going to talk about is the serum ferritin. Now, a serum ferritin, ferritin is basically a storage protein for the iron. This tends to be more of a sensitive marker, meaning, if it's low, then Ida can be confirmed without having to draw any other ion studies. In true Ida, we're going to find the level to be low. Now there is no consensus on what is that low level is. Most guidelines kind of put a mark at less than 30. We're. But there are some clinicians that look at like 40 of ferritin being kind of low as well. But keep in mind, we don't treat the numbers. We treat the patient. So we got to look at some of those signs and symptoms we talked about earlier as well. One thing to consider about ferritin that it's also an acute phase, reactant. So depending on what other conditions patient may be experiencing, such as any acute inflammation, maybe their RA is flaring up. Maybe they're having infection, maybe they have covid, 19 infection, liver disease, acute heart failure, you know, they're going through recent diagnosis of cancer malignancy that could also impact the ferritin level. Speaker 1 15:47 Yeah, so one way to think about that ferritin is that if it's low, it's pretty confirmatory. If it's normal or high, it may not be because it's acute, an acute phase reactant. It goes up in response to other things that aren't related to iron deficiency anemia, you know, Dr. Patel, one thing you know, when I was a student, it seemed intuitive that for iron deficiency anemia, why wouldn't you just check the serum iron? That sounds like the best lab to see if you don't have enough iron, right? Serum iron is literally the amount of iron circulating in your blood that's bound to a protein called transferrin, because it can't just be on its own. But what's interesting is that we don't do that because serum iron alone is part of our diagnostic workup. But other things can make serum iron low that aren't iron deficiency. The main one is going to be anemia of chronic disease, and this is an issue where the serum iron is low, but the patient actually has a ton of stored iron that we'll talk about in a little bit. So if you gave them iron, you would actually not be helping their anemia of chronic disease. Also, someone just had a recent meal, they could potentially have an artificially high serum iron level, because they literally just ate their red meat or whatever, and by doing that, their level could be falsely elevated. So you do have to be careful with this one, but it's another thing that we can look at. And in true iron deficiency anemia, this should be low, less than 60, right? Dr. Khyati Patel 17:13 In some cases, to avoid any kind of impact from food or meal, they would recommend that this level be drawn more on a fasting basis. But most institutions don't do that. So something to be kept in mind in relation to when we are drawing it from when patient had their last meal. The next one is total iron binding capacity. Its acronym is TIBC. You may see that as part of your lab workup, the 350 to 400 mark, or anything higher than that is indicative of Ida. If it's below 350 it's normal. And what this really means is that there is more binding sites on the red blood cells for the iron, but the iron is not there, so that's why this value is more higher. Kind of like the seed is there, but the occupant of the seat is missing. Speaker 1 18:08 Dr. Patello would make sense, then that we might want to compare the amount of seats that we have versus the amount of iron or amount of people that we have, right. And that ratio may be important, and that ratio is another thing that most labs are going to report right. Dr. Khyati Patel 18:23 That's right. And this ratio is called serum transferring saturation. Sometimes, if they don't report it, there is a way you can calculate it. If your iron studies had, you know, captured the serum iron and the tipc. And so basically, as you said, Dr. Kane, this is a ratio of serum iron and total binding capacity times the 100 again, because of the iron and the food impact we talked about earlier, there's some belief that, you know, a fasting sample might be a little bit more accurate. In a nutshell, less than 20 of T sat is considered low and but if it's like, if it's lower than that, then it's more confirmatory that it's definitely Ida. But less than 20 is considered to be kind of like an acceptable cut off. I've even seen like less than equal to 19 to be a cut off as well. Speaker 1 19:15 And as we'll talk about later, doctor tell this is one of the things that we monitor when we do give patients iron to make sure that we get that t set up to about 20% to make sure that the seats of iron that are there are being filled with the iron supplements that we're giving the patient. Dr. Khyati Patel 19:32 Yeah, absolutely and the last, but not the least. You know, some labs, and I've not seen this in my practice, Dr. Kane, but will also capture serum transferrin. Now, transferrin, as we discussed earlier, is a transfer protein that carries the iron. This is not drawn as part of your normal diagnostic workup, but it could be drawn on the side. Again, your liver ends up producing more serum transferrin in response to the decrease. Iron store, so we might see the total serum transfer and value to be higher, yeah. Speaker 1 20:08 And other things to think about. You might do an occult blood stool sample to just look to see if there is kind of hidden blood or occult means that you can't see it with your eye, but there's blood in the stool. But typically what we're looking at here is that you do your CBC and you say, hey, they're anemic. If you already suspect iron deficiency anemia, you might do the iron study with your CBC or maybe just your ferritin alone. And then in special circumstances, there are some more advanced tests that aren't typically done, but could be done so that these are things like a soluble transfer and receptor, ferritin, index, reticulocyte, hemoglobin, content, bone marrow, iron, stain, CRP. There's all sorts of other things out there, but the run of the mill, normal patient is just going to be the CBC with iron study, or CBC with ferritin. Dr. Khyati Patel 20:53 That's absolutely right. And this is something to keep in mind too, that you know, while you throw a bunch of tests at patient, you have to understand the clinical utility of these tests. And as we as we learn, sometimes you want to just draw the more confirmatory tests, like the ferritin even, rather than drawing, drawing all the iron studies, maybe it's more of a reflex test that you can consider doing in some cases. And I saw this in the literature. Dr. Kane, this is really interesting. Obviously, laboratory access in United States is not tend to be an issue, but in developing countries, you know that could be a problem, where people have to travel so far to get labs done. Sometimes the clinicians will confirm the diagnosis of Ida by just doing a therapeutic trial of iron. So technically, just like it sounds, the patient is going to get a therapeutic trial of iron supplement, let's just say ferrous sulfate, 325, milligram once daily for about three weeks, and then they will look for resolution of the symptoms. And if then lab access becomes available, they may see increased numbers of reticulocytes and new RBC production, and then maybe the hemoglobin starts to, you know, creep up towards normalization. So that is also done, if you don't want to do baseline lab tests as well. Speaker 1 22:17 Yeah, I think you know, for the student that is going on API rotations, or for the practicing pharmacist that needs that refresher on iron deficiency anemia, the main things that are my takeaways, Dr. Patel, are we're looking at for a serum ferritin less than 30, typically a T sat less than, or equal to 19, and then, especially in those more developing countries. Or if the diagnosis is not completely clear, even that three week therapeutic trial of iron is kind of our approach here. Dr. Khyati Patel 22:45 That's right. So moving on from diagnostics and looking at risk factors and patient evaluation, let's talk about treatment and something to be aware of, what our treatment goals are for IDA is that it's very treatable. You know, with the resources that we have, patients should improve or have complete resolution of symptom and return to normal quality of life. That is, if they don't have any other underlying or chronic diseases that impact anemia like CKD. Speaker 1 23:19 You know, in terms of some of our goals, those are going to be symptom improvement, back to quality of life, hopefully they don't need any blood transfusions. If there is some underlying deficiency, like an iron deficiency, we want to repeat that up and show on lab values that those are better, and then we're going to continue that therapy until we reach those goals. So in the case of iron deficient anemia, we're looking for that serum ferritin to get back to a normal level. Those iron stores need to be filled up, right? Dr. Khyati Patel 23:47 And eventually that would also mean that the hemoglobin will also return to the normal value. So we kind of look an eye on those as well. We always start with talking about non farm treatment options before we go to the farm. But I want to set the stage and say that some of these food based items that we talk about that contain iron are good for maintenance. This is considered more of that recommended daily allowance. What should be part of your nutrition. If your patient has true Ida, expecting them to eat this food would not solve or replenish the amount that they need, but I think it's still important that we talk about what a diversified diet should look like. So a recommended daily allowance for an adult for iron is about eight milligrams daily, compared to 30 to 60 milligrams daily during pregnancy. So imagine how much iron burden or load that it requires to sustain New Life, Speaker 1 24:47 lots more. And you know, in terms of dietary iron, we have two main forms, heme and non heme, heme. You're going to see this mostly in meats, and this is better absorbed, but meats also contain. Non heme as well. So examples of some of those would be your typical meats, like red meat and things like that. Seafood, poultry, oysters, chicken, beef, all that good stuff is going to have both heme and non heme. And the heme is going to be a little bit better absorbed Dr. Khyati Patel 25:15 right in our most of the plant based products, such as, you know, white beans or spinach. Remember Popeye, the Sailor Man, lentils, tomatoes, cashew nuts and green peas and stuff, as well as our breakfast cereals, which are usually fortified with iron and over the counter supplements. These are forms of non heme supplements. Yeah. Speaker 1 25:39 And then another thing to just think about is that acidic environments help iron absorb better, and we also know that vitamin C or ascorbic acid can help improve iron absorption. So sometimes, if oral iron supplements are not working, we could consider adding on ascorbic acid or vitamin C. So this could also be a dietary source as well, where someone might take in a little bit more vitamin C, something like oranges, orange juice, things like that to kind of help with that iron absorption. Dr. Khyati Patel 26:10 So talking about things that can help with the absorption, things that decrease iron absorptions are things like tea or milk. And I'm thinking milk, Dr. Kane, because it has calcium, and then calcium and iron usually fight for absorption. So something to consider maybe separate the consumption of milk based items, if you're taking iron supplements by a couple of hours Speaker 1 26:33 and Dr. Patel, like you said, these dietary changes are more of the maintenance phase of someone who had iron deficiency anemia, you treated them, you repeated their stores, and now they don't want to be on iron supplements forever. They might need to make some dietary changes to make sure that they don't get low again. But for that patient who currently has iron deficiency anemia, the treatment is to give them a supplement, as opposed to just dietary changes alone. And typically, we're looking at giving the patient around 100 to 200 milligrams of elemental iron every day. And that can be for several months, maybe three to six months, until that hemoglobin is back and their iron stores are back to normal to give a number to it. So a typical scenario would be someone who goes to the pharmacy picks up ferrous sulfate. It says 325 milligrams. But of those 325 milligrams of ferrous sulfate, the amount of elemental iron is only 65 milligrams per tablet. So that means that to get to your 100 to 200 milligrams of elemental iron per day, you're going to have to take a couple of those tablets a day. And we'll talk about that. That can be challenging from a tolerance standpoint, but there's a ton of different therapies out there a bunch of different ways to kind of dose it, and that's actually a huge role the pharmacist to pick the best product for a given patient. Yeah. Dr. Khyati Patel 27:50 And interestingly enough, you know, all of these different formulations that are available have different percentage or amount of elemental iron in them, and so the strength as well as the frequency of tablets that patient might be taking may differ based on the product they pick up. However, one thing to keep in mind that our body at a time can absorb only 25 milligram of elemental iron. So even if you're taking a larger elemental iron dose, there is a plateau absorption effect that happens too. So keep that in mind, that number really doesn't mean anything as much as it means that patient's taking on a consistent basis. Speaker 1 28:29 So Dr. Mattel, what are some of the like? What are other examples besides ferrous sulfate, which I think most people are familiar with, what are some other products, and why might you pick any of the other ones over the kind of standard bearer, iron sulfate that is readily available and very commonly used, right? Dr. Khyati Patel 28:45 So as you mentioned, iron sulfate is the most common. Keep in mind, it's also available in some liquid formulation, like oral solution or elixir. We won't go and talk about how nasty they taste. Dr. Kane, but flavoring options are always there. The slow release Fe is also a type of iron sulfate which is exicated. There is some claim that it does help with some of the GI side effects. However, keep in mind, most of the iron absorption needs to happen in the stomach, and so if you're doing a slow fe, you're delaying the absorption until it reaches the small intestine, and then it doesn't absorb the iron that is supposed to absorb. So there is some contention with the use of that slow Fe product. In addition to the sulfate products, we have the fumarate salt, the citrate salt, the gluconate salt. We also have carbonyl iron as well as polysaccharide iron. All of these have varying amount of elemental irons in it. And the kind of bottom line here is that your ferrous salts of iron are better bioavailable than your ferric and so I almost always haven't seen as much dispensing. Consumption of the fumarate, citric gluconate, or any other type besides the sulfate. Speaker 1 30:05 Yeah, I'm the same way. I've seen a little bit of the non ferrous sulfate products. But 999, times out of 100 when someone is on an iron product, that typically they're going to see the first sulfate Dr. Khyati Patel 30:15 product, right? And then, if you think about more bang for the buck in terms of that elemental iron dose we want patient to take with the limited, you know, frequency, I tended to go with the polysaccharide iron complex, which has 46% which is kind of the highest of all the oral iron formulations that are out there. However, it tends to be a little bit more expensive. So keep in mind, you know what your patients can afford as well as these are over the counter therapies they most likely will have to pay out of pocket. Speaker 1 30:47 And as we mentioned, in terms of the dose that a patient needs to take, a pharmacist does play an important role in acknowledging, or kind of calculating, how much of the iron is in the iron salt. So as an example, you mentioned Dr. Patel ferrous sulfate, only 20% of that is iron. So of the 325 milligrams of ferrous sulfate, you only get 65 milligrams of elemental iron. And it's the elemental iron that we use to kind of dose the patient. So that's one thing to think about for all of these. But as we go up on that dose, the patient may experience some side effects that make it so that we can't titrate the dose because of intolerances. So examples could be constipation, although diarrhea is also a potential problem, I would say constipation is more common. Patients may also see dark stools, which could be kind of alarming if they had a recent GI bleed, for example, which also can present as dark stools. This is pretty irritating to the gut lining. So nausea, vomiting, Flagellants, just pain, epigastric pain or distress, and it tastes bad, like a metallic taste, which, for obvious reasons, it tastes metallic. All of these are reasons why it may be difficult for patients to tolerate iron therapy, and we may have to go down on their dose and be a little bit slower in terms of how quickly we replete their iron stores. Yeah. Dr. Khyati Patel 32:03 And one thing about the dark stools I want to mention is it's a really important patient education point, because if your patient is also on anti platelets or anti coagulants, we are telling them to keep an eye on those dark tarry stools. Well, they are on iron as well. So they should be able to differentiate whether these are, like the iron therapy–based dark tarry stools, or they are really having some sort of GI bleed, because they are on these additional, you know, anti platelet, anticoagulant like therapies, and they're having a true GI bleed. So something for your patients to definitely keep in mind. And I have a couple of patients like those in the clinic, and they tell me, Oh, I know. I know what they look like, you know, based on what I'm having. So very important point to put across to your patients, Speaker 1 32:47 yeah, and other things, terms of role of a pharmacist for thinking drug interactions as well, dr, tell what kind of drug interactions come to your mind when you think about iron, right? Dr. Khyati Patel 32:57 So a lot of absorption based interactions that come across for iron. You already talked about. One of the helpful interaction is that the increased acidity with vitamin C may improve the absorption, but on the other side, the decreased acidity of the stomach, which is induced by drugs like PPIs or your h2 blockers or antacids, they're going to repair the absorption of iron products. Additional ones include tetracycline, xocycline and those cholesterol mean type powders. Normally, we ask patients to separate the consumption of iron either two hours before these drugs or four hours post the antacids like products. Speaker 1 33:42 And then part of those interactions are chelation interactions, where the divalent, or trivalent cations can actually bind to other drugs. So the main ones that come to my mind are tetracyclines, like doxycycline would be an example. Fluoroquinolones, things like that, where the iron literally binds to those and then neither one gets absorbed. So if you're taking that fluoroquinol and antibiotic with your iron, you're not going to absorb as much of that Ciprofloxacin or levofloxacin or something to that effect, right? Dr. Khyati Patel 34:10 And therefore that two hours before or four hours after separation is a very important patient education point as well, and some of the overall consideration to be made for the oral iron therapy is that this is normally the first go to therapy, unless you have indications for IV, which is the parenteral type of iron, because it's, you know, relatively effective, a patient is able to tolerate it. You know, patients can go over the counter and purchase these products. They're relatively cheap and safe for most patients. Across the board, if you're looking at various formulations we discussed, they're equally effective. You're just going to have to make sure the frequency at the dose based on the elemental iron. But keep in mind, your body can only absorb 25 milligram of elemental iron. At a time, so you might have to just balance out the frequency with the patient's tolerance of the dose that you're developing for them. Speaker 1 35:11 And as we mentioned, an acidic environment is better. So taking it on an empty stomach, or even taking it with orange juice or vitamin C ascorbic acid, that could be helpful. As you mentioned, Dr. Patel, the ferrous salts may be more bioavailable than the ferric salts. And then for that patient that you are having some difficulty, escalating their dose to whatever target dose you had in mind for them, you probably should start low and then increase slowly to hopefully help them tolerate the drug better. Obviously, if you start too aggressively, and you kind of lose their trust, and they don't want to take it at all, that can be very counterproductive. Dr. Khyati Patel 35:48 And actually, some studies, if patients were started at a higher dose rather than starting at a lower dose, to say, like, I'm giving you all that elemental iron that you need today, right now, with this one dose, they actually found that the iron stores did not reflect very well compared to those who started with slow and then increased it slowly Speaker 1 36:12 and then Dr. Patel, are there any other ways, especially for that patient that doesn't tolerate it? Is there any other alternative to starting low and going slow in terms of a dosing strategy? Dr. Khyati Patel 36:21 Yeah, there's some small trials that have shown that taking it every other day does provide a little bit more adherence. Maybe patient remembers to take it a little bit more diligently, too, because they know they have to take it on a Monday, Wednesday and a Friday if they're separating it that way. And for those reason, there is some better outcomes in patients who can't tolerate everyday dosing, that every other day dosing is okay to use as well. Speaker 1 36:48 And what about taking with food? Is that an option? Because I feel like that's kind of our go to standard bearer when we say that a medication is harder on your stomach. Is that an option with iron? Dr. Khyati Patel 36:59 So normally, if you know you have a iron therapy, naive patient, we want to start with empty stomach, because that acidity does help with the iron. But if they end up developing some GI side effects, then it is okay to take with food. But keep in mind, if they're taking it with food, the absorption is impaired, and they might end up needing a little bit more dose or more frequent dosing for the day. Speaker 1 37:27 So Dr. Matt, clearly, there's a lot of oral products. Some patients are going to tolerate the oral very well, but we have some strategies that we probably should implement. But is there a scenario in which we would give parenteral or IV iron, as opposed to those oral products. Absolutely. Dr. Khyati Patel 37:43 Dr. Kane, I think the utility of parenteral iron therapy is there for those who don't benefit from oral iron therapy. And I think there is some concerns on the clinicians part, on using the parental therapy, because back in the day, we used to have this high molecular weight iron dextran product that ended up causing a lot of infusion related reactions and anaphylactic reactions, and that kind of scared the clinicians off. However, we have plenty of different type of IV iron products in the market right now that are considered really safe and should be used if indicated and so talking about what patients are indicated to receive these therapies are those who diligently tried oral therapy, but their iron stores are not moving. Maybe they tried as much as they could on the oral doses, but they're intolerant because of the GI side effects, and they just can't take the oral therapy anymore. Maybe they have severe malabsorption issues, such as inflammatory bowel disease, or they got gastric bypass for weight loss, where their absorption, or the needs for the iron is very high and absorption is really low. And in that cases, you know what, they're taking it by mouth. It's not going to cut it. They probably will need a different route in other cases, such as CKD, where a patient is either not on dialysis or on dialysis again, the patient may be receiving an erythropoietin‑stimulating agent or may not be receiving it. Parenteral iron therapies are advised Speaker 1 39:19 and Dr. Patel, you know, on the inpatient side, giving IV anything is not a big deal, and we'll talk about it later. The main product that I see in my practice is iron sucrose (Venofer), and it's pretty interesting, because it looks like you're giving coffee to the patient. It's like a very dark IV solution. On the outpatient side, is this an option, or are there kind of nuances to giving it IV as an outpatient therapy? Dr. Khyati Patel 39:45 So I get to see iron sucrose infusions on an outpatient basis, very commonly, Dr. Kane. So definitely formulary wise, you know that's been more of that safer product and non formulary cost wise too. It's a. A little bit better. And the outpatient side, we will schedule their infusions at maybe an infusion center or day treatment center, where they can come and complete the complete the therapies. And so, yeah, the IVR and products are also kind of good substitute for those who don't believe in transfusions or want to lessen the burden of transfusion therapies. And then, in just any cases, they have low iron, but they have a surgery coming up, right? And so we need to replenish their stores faster. We can use the IV iron products in the global sense. The IV iron products are usually administered IV push or infusion. A lot of them are now being able to dose in a full doses over maybe a longer infusion time. However, a lot of them are still required to be dosed in divided fashion, so patients may have to come back to the infusion center because they're receiving it in smaller doses. There is a lot of equations out there. Dr. Kane to calculate what dose patients need. Generally, if you're calculating your patient needing more than 1000 milligrams per the total infusion period, there's some evidence that more than 1000 milligram doses are not as useful, and so some sites, instead of calculating patient specific dose, would just go ahead and use that 1000 milligram dose and then divvy them up over a few infusions. Yeah, and Speaker 1 41:27 Dr. Patel, I really want to highlight what you said there. You know, for someone who's more used to the oral outpatient iron supplementation strategy, those are patients that are taking, you know, one, two or three doses every day for at least three weeks before you even recheck the hemoglobin. But oftentimes they're going to be on that therapy for several months. And we're contrasting that when someone is getting one, two, maybe three, but likely two or one doses of IV iron therapy, and then they're kind of done, like they've supplemented based on that IV approach. So it's kind of a one or two and done strategy versus the oral, which is going to be over a longer period of time. Dr. Khyati Patel 42:06 Yeah, and this is more of an attractive point, especially from patient tolerance perspective. Those who were on oral, and you know, it didn't move the needle at all. When they start to receive IV, we're going to stop their oral, because we don't want to do both therapies at the same time. Once the IV treatment is done, they can go back to receiving the oral if they were severely depleted to begin with. However, in most cases, they may not need oral iron therapy afterwards. Speaker 1 42:35 So Dr. Mattel, you know, we talked about risk factors for anemia, and one of those risk factors is menstruation and heavy menstrual flow and stuff like that. In pregnant women, they're going to need a lot more iron as well, because they have a developing fetus that is going to require that iron. What is our strategy in that pregnant population in terms of iron supplementation? Dr. Khyati Patel 42:58 Absolutely, and keep in mind, pregnant ladies have a lot of GI issues to begin with, so having them take the optimal po dose that adds more GI issues is not feasible, and that's where the IVR and therapy comes in handy. We don't have a whole lot of data in the first trimester used, but the second and third trimester, these therapies could be used safely. And then one thing to keep in mind, Dr. Kane, we will summarize the side effects of the IV iron in general, but there are some infusion related reactions that patient can mount. And therefore, in some infusion centers, patients may receive pre medications such as diphenhydramine or prednisone or methyl prednisolone or an h2 blocker. Again, this is not done on a consistent basis, but it's more of an infusion protocol. Some clinicians say that they don't even use some of these pre medications unless patient develops. So it's more of an refractory order that's added and only used as needed, but not kind of given to patient as a pre medication, but rather as a rescue medication. Speaker 1 44:07 Dr. Patel, is there a formulation that is more prone to that, and therefore we might be more likely to see that pre medication with a given iron formulation? Dr. Khyati Patel 44:17 Yeah, absolutely so. There are a couple of iron formulations were related to a little bit more, higher risk of allergic slash anaphylaxis reaction, or that infusion related reaction that's going to be your low molecular weight iron dextran, the Infed, as well as your the ferumoxytol (Feraheme) products. These products are therefore infused over a certain period of time, and then patients is also going to be watched after the infusion. So for example, for ferumoxytol, the patient's going to be observed for about 30 minutes post‑infusion, and then for the iron dextran infusion, patients may even need one hour post infusion. Oxygen observation, and in some cases, because of these black box warnings of anaphylaxis on these two products, especially for the iron dextran, it is recommended that we do a test dose for the patient. So we're talking about 25 milligram. That's about point five ml. You give it to the patient over IV, push for at least 32nd and then you observe the patient for one hour to see if they mount any type of anaphylaxis reaction. So we have some of these strategies, but honestly we have better products, such as iron, sucrose, as you mentioned, which has much less of these infusion related anaphylaxis or infusion related reactions, as well as the ferric carboxymaltose, also called FCM or Injectafer, and these products are used and wide variety of different type of indications. Some are non primary indications, but most of these are approved for CKD patients with or without dialysis, in some cases, patients who have either cancer induced or chemo induced Ida as well. Speaker 1 46:10 So Dr. Patel, I know that there's even more iron products out there on the market. You want to just briefly mention at least the brand and generic of those other iron products in case someone sees them in clinical practice. Dr. Khyati Patel 46:20 Yeah, absolutely. We have some ferric gluconate based products, new lucid, which has a little bit less percent of elemental iron. We have the sodium ferric gluconate, which is Ferrlecit, which has equal amount of elemental iron as the Nulecit. And then, last but not the least, this is a very new product, Triferic, which is a ferric pyrophosphate citrate, which is only indicated for patients with CKD who has hemodialysis in place, because this product is actually mixed with the dialysate and then infused to the patient. So it's not a separate infusion, but you mix it in the dialysate, and the patient gets their phosphate as well as their heme supplementation, interesting. Speaker 1 47:05 And as we mentioned, from a side effect standpoint, the main thing is going to be, or the main concern that is going to be on everyone's mind is the anaphylactic, or allergic type reaction. And this is actually really rare, especially for these newer iron products. So we're looking at less than one in 200,000 patients, if patients have a history of immune mediated diseases, so autoimmune disorders or a bunch of drug allergies, they're probably more likely to experience this. And that's one of the reasons why test dose can be considered, really, for all of that, the iron products, if the patient is at high risk. So iron dextrin is best described for that test dose. But if someone has some of these kind of immune mediated diseases, maybe they would also be considered for that right. Dr. Khyati Patel 47:48 And then these are the patients who might be also candidate for those pre medications, so not used as a rescue therapy, but that kind of given the pre medication to begin with and post observation would also be helpful. But I want to go back to my point in addressing that, the anaphylactic and allergic reaction with the new type of IV products are considerably less than that high molecular iron dextran we used to have in the market, which is no longer in the market because of those side effects, and all the other products have much less of these reactions kind of connected to this anaphylactic or allergic reaction is the infusion related reaction, and it it really is a fine line to detect the infusion related reaction, and then the anaphylactic reaction, the infusion related reaction, again, happens in a very low frequency. We're talking about, point five to 1% of the infusions, normally described as the myalgia, the arthralgia, the chills, the flushing, the fever. Talk about, maybe like a flu, like symptoms. And this is, again, we're either stopping the infusion, giving the patient the rest, maybe giving some of those rescue medications, and then, you know, re restarting the infusion. Those type of strategies can help manage the these type of reactions. Speaker 1 49:09 So Doctor Patel, besides anaphylaxis and infusion related reactions and allergic reactions, are there any other side effects of IV iron that we should be aware of? Dr. Khyati Patel 49:18 Yes, absolutely. So thankfully, no GI issues, right? Because we are bypassing that route completely, but we get to see additional issues such as hypotension, some headache, dizziness, maybe syncopal episodes, and in some cases, dyspnea has been noted. There's documentation of iron overload, and therefore, kind of going back to the drawing board and calculating the patient's iron deficit or not giving higher doses is important. But I bet you that your hospital formulary protocols, as well as your infusion protocols, will not let you dose more iron because they are always capped off and so. The issue of iron overload is occurring less and less because we are using more of protocol based dosing. So really, Speaker 1 50:07 regardless of oral or IV, we want to make sure that we're appropriately monitoring these patients to make sure that their iron deficiency anemia improves. Right? So from a symptom standpoint, what might patients expect from a symptom improvement standpoint, fairly early on in their therapy. Dr. Patel, right? Dr. Khyati Patel 50:24 So these are good points for patients to also keep in mind to see if they're getting benefits from the treatment. So we're talking about pica behaviors, again, eating non food items, or pagophagia, which is eating ice. It kind of disappears as soon as patient starts therapy. I'm talking maybe one or two days of starting the therapy, patients start to feel better, like the energy level kind of returns. Feels a little bit like they're returning back to their normal being within first few days of the treatment. And then remember the glassiness or the smoothness of the tongue we talked about, where the papillas are removed, or they start to return within weeks to months of being on therapy. Speaker 1 51:07 And then, from a CBC standpoint, hemoglobin hematocrit, that should really start to improve after one to two weeks, but it's going to take about six to eight weeks, or up to two months for a full improvement of that hemoglobin on the CBC, Dr. Khyati Patel 51:22 right, and then we could consider repeating the iron studies within about four weeks after the treatment starts, because we may start to see some of those indicators, like the ferritin and the TSAT, start to change at that time. Speaker 1 51:38 Hopefully patients are taking their iron appropriately, but if there is any concern that they're getting too much iron, what kinds of things would be we be thinking about from a iron toxicity standpoint, right? Dr. Khyati Patel 51:51 And hopefully in the modern days of dosing and protocols, we don't get to this, because these are ugly side effects. But something to keep in mind, as far as lab values for iron overload, we may see abnormal LFTs. We may see super high ferritin levels. We're talking about above 800 or very high transferring saturation. We're talking about 50% or above. And as far as we're looking at symptoms, again, no patient wants to have them, but initially they may experience GI issues like nausea, vomiting, diarrhea and cramping. However, swelling in the body, intestinal ulceration that can lead to then bleeding, and so patients may have hematochezia or hematemesis or melena could also result. So again, not good things, but again, in the world of protocol based dosing and cap dosing, we don't get to see there these type of toxicities. Speaker 1 52:50 So Dr. Patel, we've really run the gambit from understanding risk factors, e allergy, diagnosis, treatment, monitoring of our treatment. Why don't we go back to our patient case? So you provided a patient case of TR, what are some things that stick up to you in terms of the presentation of the patient? Dr. Khyati Patel 53:09 So in my practice, I'll be looking at this patient and looking at risk factors, such as patient had multiparity, so they have multiple pregnancies. We talked about pregnancies using a lot more iron to sustain the new life. Patient is also having some irregularities in their menstrual cycle, including some heavy menses. So those two are the ones that sticking out to me the most. Some of the symptoms that I could say this is probably going in the direction of anemia, is the patient's complaining of fatigue and weakness and shortness of breath on, you know, activity and exertion and then some of the lab values are also indicative, right? So our hemoglobin of 11.5 is considered to be low. We establish that anything, any ferritin value below 30, this patient has 20, is considered low. TSAT is at 17% again below 19 or 20 is considered low. The iron binding sites are elevated at 450 and the serum iron concentration below 60 is usually low. This patient had at 45 Speaker 1 54:18 and you know, from a diagnosis standpoint, certainly iron deficiency anemia is highest up on our differential other sign, symptoms, lab values could be confirmatory. I think at this point, we probably have most of what we need. Don't you think? Dr. Khyati Patel 54:31 Yeah, I think we do. It looks like, you know, we're not just looking at the labs again. It's important to look at the patient's symptoms as well as the risk factors, but these are all good tattle signs that it is leaning towards the IDA. Looking at ferritin alone, can tell us that this is diagnostic enough for having Ida in addition to the symptoms. So talking about some of the treatment options that patients may have now, she does have. Symptoms of fatigue, weakness, and, you know, shortness of breath. I don't see any indications, or at least immediate indications, for parenteral products, so it's fairly okay for this patient to start with the PO therapy again. As we said, we're going to start with the lower doses and get to that optimal dose as patient tolerates it. We're going to provide all that education on GI issues. You know, watching out for directory stools. Tell the patient to try to take it an empty stomach for improved absorption, or maybe throw in a little bit of orange juice. But most importantly, this patient's on antacid Dr. Kane, so we're going to have to teach her to separate the dosing of iron products from her antacids whenever she takes it at least two hours before or four hours after, to make sure that there is no impairment and absorption. Speaker 1 55:50 Yeah, and you know, if we gave her something like ferrous sulfate, 325 milligrams once a day, that would be a pretty reasonable starting dose. She's that terribly anemic. Her tea set is not incredibly low. I don't know that it would make any sense to be more aggressive with her dosing, but you could always go up, right? And we talked about dose titration up is probably better than going too heavy and too aggressive up front, right? Absolutely. Dr. Khyati Patel 56:14 So something to help patient tolerate this better, that would be the best approach. Speaker 1 56:19 Then I assume in a couple weeks, we'll probably give her a phone call make sure that she's feeling better or feeling not worse, at least. And then in about a month, probably would want to repeat at least a CBC, maybe even iron studies, to kind of see those numbers, hopefully improving, Dr. Khyati Patel 56:35 right and if she is getting benefit and feeling better, and the you know, the labs are trending up in the in the right direction, then we may continue the therapy until those iron stores are replenished. We're talking about the good ferritin values, you know, the good hemoglobin, and pretty much complete resolution of the symptoms, because this patient doesn't really have any chronic issues that would keep her on that low side of the hemoglobin. Speaker 1 57:02 And of course, if she can't tolerate that ferrous sulfate, and we try other strategies to help her tolerate it, and they're not working, or her labs don't get better, potentially we could consider IV therapy for her. Dr. Khyati Patel 57:16 Absolutely, there are a lot of safe options for IV iron therapies are out there convenient options. I think really the limitation in selecting the IV therapy is based on what the your institution carries it and what the patient insurance covers it. But besides that, and what probably fits in the patient's schedule, as far as the frequency of dosing goes. But other than that, IV therapies are becoming more common and common Speaker 1 57:44 so Dr. Patel, I think this was an amazing comprehensive review of iron deficiency anemia, spanning from risk factors all the way to treatment and monitoring. We do have some show notes. If listeners want to check those out. They can visit our website, at HelixTalk.com and again, this is episode 149 we're also on Twitter, where we have clinical pearls from this episode and previous episodes that listeners are welcome to take a look at, at HelixTalk on Twitter. And finally, we love the five star reviews in iTunes, so keep those coming. So with that, I'm Dr Dr. Khyati Patel 58:15 Kayn and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 58:19 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 58:30 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.