Anemia 101: A Hematologist's Guide to Understanding Symptoms, Iron, B12, and Folate Deficiencies

Anemia 101: A Hematologist's Guide To Understanding Symptoms, Iron, B12, And Folate Deficiencies With Dr. Daniel Kobrinski

This is anemia 101 with Dr. Daniel Kobrinski. Welcome to the show. This episode is going to be all about anemia, a condition that affects millions of people, but it is often misunderstood or overlooked. I am so excited to have you join us, Dr. Kobrinski. Dr. Kobrinski is a leading hematologist and oncologist in North Florida and has years of experience in this field, which brings both deep medical expertise and a passion for helping patients better understand their health. Beyond his clinical work, he also has a podcast called The Rick & Danny Show, which you should definitely check out. Thanks so much for joining us. I know I have given a bit of your background, but I would love for you to give a little intro in your own words.

Thanks so much for having me. When I heard that I had the opportunity to come on the podcast with you and just talk about a topic like anemia, I jumped at the opportunity. It is a great opportunity to talk to patients, talk to anyone who is tuning in, who is interested in just learning more about it and how common it is, and how we approach diagnosis and management. It will be a good talk for people to listen to and get some salient points on how we manage this. You are right. I joined Cancer Specialists in North Florida, which is a large community practice here in Jacksonville, Florida.

I joined in 2018. I moved from Chicago. In the summer of 2018, I did my medical training at Loyola in Chicago. I did both internal medicine and hematology and oncology fellowships at Loyola in Chicago. My wife originally grew up in Orlando, Florida, and she has a lot of her family still in Orlando. When we were looking at opportunities for starting my career, Florida was kind of top of mind.

I came down here, and I applied to a number of opportunities in Florida. The Jacksonville opportunity at Cancer Specialists in North Florida stood out, I think, because of the location, because of being a private practice, being able to practice both hematology and medical oncology, and serving the Jacksonville community. It just sounded like a great opportunity. I joined the practice in 2018.

We do community medical oncology and hematology. We see pretty much any diagnosis you can think of in those two specialties. We do sometimes have to refer out to larger academic centers and tertiary care centers if appropriate. In terms of managing the bread-and-butter hematology topics like anemia, we do that every day in the clinic, and it is something I enjoy doing.

Just a little bit more background on myself. I have two children, a twelve-year-old and an eight-year-old, with my beautiful wife, Hetal. She is not in the medical field. She is a marketing manager for Motorola. All my patients ask me, "What does your wife do? In medicine?” No, she is a business lady, and she has been in business a long time. We are enjoying our life here in Jacksonville. It has been a great eight years now.

Eight years already. At the beach location, too. You cannot beat the beach. For those in Jacksonville, you know, he is at the beach location, but it is great. Close to the ocean. 

Neptune Beach. We are just south of the library, close to Atlantic Boulevard. We moved to this location, I think it has been three years now. It might even be a little longer than that, but easy access for the Atlantic Beach population, Neptune Beach. Our Ponte Vedra patients come up just up A1A, and it is a nice setting.

A nice spot. I mean, you could walk so close to that town center now, too. You guys probably have more restaurant options and everything. 

We love going out to the restaurants. You can find a little bit of everything, which is great. 

Let us get into it for just an overall view of anemia. What exactly is anemia?

Anemia generally is either a low red blood cell count or other parameters that measure red blood cells in the circulation. That could be your hemoglobin level, which is more of a concentration of a component of the red blood cells. Hematocrit is another way of looking at it, which is given as a percentage. It is basically that you have a reduced or low amount of red blood cells in your circulation compared to the normal population.

Tweet: Anemia is generally defined as a low red blood cell count or low levels of key red blood cell measurements, such as hemoglobin, which reflects the concentration of oxygen-carrying proteins in the blood.

Whenever you get a low or a high parameter on your blood test, no matter what it is, it is always compared to the general population or the population that is being studied at any given lab. Actually, a lab, whether it is Quest, Labcorp, or our lab, each lab sets its normal distribution or its reference ranges for any particular lab. For anemia, yes, low red blood cell count or hemoglobin. 

In terms of symptoms, what symptoms do people usually have for anemia?

Symptoms Of Anemia

General symptoms of anemia overlap with a lot of other medical conditions or other diseases that could also manifest as anemia. You have fatigue as probably the number one symptom that people complain about who are anemic, and varying degrees of fatigue. It could be profound fatigue where they do not feel like getting up to do their activities of daily living, or it could be just mild fatigue. "I just get tired at the end of the day. I have less exercise tolerance," those types of things. Patients can have their sleep affected.

Insomnia can be an issue with people with anemia, sometimes restless leg syndrome, particularly with iron deficiency. People can have that as a manifestation. Patients can feel restless, just general restlessness, general anxiety, or trouble concentrating. Those can be signs of anemia. They really are non-specific, I would say, for one particular disease. It is certainly worthwhile getting a workup and ruling out anemia when you are feeling symptoms such as those.

It is hard because it would be, sometimes there are symptoms where you are like, "This would be a higher chance that you have this disease." It is overarching because I feel like, with anemia, your body is having to work harder. That will just then manifest in so many different ways. Your heart racing, and people can feel a little more anxious, or they can feel more tired because again, their body is working in overdrive, and they might not be sleeping, so it just kind of overlaps with so many things. What is good is that you can diagnose it pretty easily. You get a hemoglobin, and get your labs, and then you can see. It is also easy to rule it out if people are having these vague symptoms to get it worked up, which is good.

The symptoms that some people just elaborate on that do not necessarily associate with anemia, migraine headaches sometimes can be associated with anemia. The restlessness, as we talked about, trouble concentrating, even independent of fatigue, people might just feel foggy, like they cannot think quickly on their feet, or come up with the answer. By no means do I mean that everyone having those symptoms has anemia, but you should certainly work it up. Because the symptoms overlap with other conditions, you just have to do a thorough investigation of the symptoms. A quick CBC to rule out anemia is an easy thing to do. 

Almost every doctor can order a CBC, right? It is a very common workup. It is like in standard labs. Very common, very easy to work up. If somebody gets a diagnosis of anemia, big picture, what would you say the most common deficiencies are that can sometimes cause that? 

The most common deficiency is going to be iron deficiency. Iron deficiency anemia, or even iron deficiency without anemia, each one of those diagnoses is one of the most common consults that we see in hematology clinics. The main causes of iron deficiency are going to be some bleeding. That could be bleeding from your gastrointestinal tract, women who have heavy menstrual bleeding, or other types of bleeding.

You have to actually rule out blood donations, because I always think about that, but sometimes forget to ask patients, "How often do you donate blood?" because that could be a cause of iron deficiency. We are completely dependent on iron from our diets. If you are not obtaining enough iron in your regular diet, then there is a chance that you could become iron-deficient over time. Iron deficiency is the most common nutrient deficiency causing anemia. We also see iron deficiency without anemia as well. 

If somebody gets a test and they are anemic, how would they then get the diagnosis of iron deficiency anemia? What lab tests?

Easy lab tests to do. There are different iron panels, Quest, and Labcorp. If you go to any lab, national lab, they will do iron panels, which give you a total iron level, an iron-binding capacity, an iron saturation, and then usually it is either included with the panel or you order it separately, a ferritin level. You read all those iron levels together to obtain a diagnosis of iron deficiency. What we normally see is that iron-deficient patients have a low total iron. That is the total amount of iron in your circulation. They have a low iron saturation, a high iron-binding capacity, and a low ferritin. Ferritin tells us how much iron a patient has stored away in their system.

Good tests to give a good diagnosis there. The next question would be, a lot of people are told to take iron. What do you usually say in terms of starting iron, oral iron supplements? A lot of people say they cannot tolerate these side effects. What are your usual recommendations for what to start with and what to change if they are having issues?

Oral Iron Supplementation Recommendations

That should be the starting point for most patients, to start with oral iron supplementation. I think because a lot of our patients know that iron infusions are an option for some patients to treat iron deficiency, a lot of the patients I see in clinic are expecting that when they come in to see me to say, "When can we set up these iron infusions?" Oral iron, I think, should be the first attempt at restoring or fixing the iron deficiency.

Iron gets absorbed in your gastrointestinal tract, so a little bit in the stomach, probably a majority in the small intestine, the duodenum. You only absorb a fraction of the amount of iron that you take in. If we recommended 65 milligrams of elemental iron, and that is just a way we describe some of the iron content in an iron pill, you might absorb a milligram or two of that. When some patients ask, "How much should I take?"

I say, "You should take as much as you can tolerate because you're not going to be able to absorb the whole 30, 40, 60 milligrams of the iron that you take." There have been numerous studies that have shown even taking oral iron every other day or three times a week can improve your iron deficiency. You do not have to take it every single day. I roll my eyes when I see patients on iron three times a day because it is just impossible for your body to absorb that much iron.

That is what I was wondering. Would it help then if they take lower doses multiple times a day, because maybe they can tolerate better, or not really?

Possibly. It is an option to try. When I see it ordered twice or three times a day, it is usually a patient who has a more severe deficiency and maybe even more moderately or severely anemic. It is worth a try. I just have not consistently seen improvements in anemia with doing that many times a day. I usually stick to once a day for most of my patients.

What about liquid iron versus oral iron? Do you see any difference there?

No, I do not really see a difference. Interestingly, the liquid iron formulations, and I think one of the old ones, Geritol, that a lot of patients took at some point in their lives who might have been iron deficient in the 70s or 80s, Geritol just has a lower amount of iron compared to your standard ferrous sulfate pill or the standard iron pill that you pick up over the counter. I tend to think that if you tolerate it and it sits okay, you are not developing severe indigestion or you are not developing severe constipation, I am okay with any formulation. I do not think, to answer your question, there is any data to show that the liquid forms absorb better than the pill forms.

What about, I know vitamin C a lot of times can help in terms of absorbing the iron. Are there other things that can help as well, or that’s all we know?

Vitamin C helps some, but there are also studies showing that it is probably not as beneficial as we think it is. There was a report in pregnant women who were taking iron supplementation for iron deficiency that showed that vitamin C did not really help improve the hemoglobin levels better than just taking iron without vitamin C. It is highly variable.

It depends on the patient, how they are taking their iron, and, to your point, whether it is better to take it with certain foods or without certain foods. The main thing you want to avoid is taking iron with other supplements or foods that compete for absorption or that may bind the iron and prevent its absorption. Usually, that is avoiding taking calcium supplements or foods high in calcium, or even zinc and magnesium, which you want to avoid.

Tweet: Avoid taking iron with supplements or foods that interfere with absorption, such as calcium, zinc, or magnesium, because they can bind to the iron and reduce how much your body absorbs.

Which can be hard, especially during pregnancy, because a lot of people get heartburn, and then you are popping Tums and calcium. People might not know that, then they're taking all their iron, and it is.

You’re right. You will take the Tums and then take the iron afterwards and not know the difference. Those are just the recommendations. I think that I have still seen patients absorb the iron well, whether they take it with food or take it without food, or take it with orange juice or do not take it with orange juice. It is not one size fits all.

For people who do tolerate oral iron supplementation, how long does it usually take for them to be able to fix their anemia?

With oral iron supplementation, I tell most of my patients that we will not likely reach our target iron goals for about two or three months. This is assuming the patient is coming in with a severe deficiency or at least a moderate deficiency. That is usually a ferritin level either in the single digits or in the teens, which, again, the ferritin reflects the iron stored in the body, how much storage iron you have.

I usually will repeat the blood work about 4 to 6 weeks after they start oral iron, just to see that we are starting to see the levels nudge or increase in the right direction. Check the labs about every other month from there to see that we are making progress and meeting our goals. What is challenging with oral iron is that even if a patient tolerates it, the challenging thing is if you have a female who has really heavy menstrual bleeding every single month, 2, 3, 4, 5 days of really heavy bleeding.

It is hard to make up for those losses with just oral iron, with their really extreme levels of menstrual bleeding. If you have losses that are hard to make up with the oral iron, that is when the IV iron infusions are much better. You can get those levels to a more adequate storage so that when the patients do have their bleeding events every month, they do not just get drained every single time.

Scenarios Warranting Intravenous Iron

That makes sense. Are there other scenarios where you kind of jump straight to the IV iron?

Yes, certain gastrointestinal disorders or conditions. Celiac disease is probably the one that stands out where patients have gluten insensitivity. It can lead to the small intestine lining having some abnormalities that prevent good absorption of iron. Those patients are probably best treated with IV iron because you are unlikely to achieve your goals with oral iron supplementation.

Any inflammatory bowel disease you have a patient with Crohn's disease or ulcerative colitis, which are inflammatory bowel diseases. A lot of patients are already having indigestion, diarrhea, constipation, a lot of gastrointestinal symptoms that you might exacerbate with oral iron use, and you just might make them feel worse with it, and at the same time have poor absorption. A lot of those patients, I just jump right to the IV iron. 

Do you have to use it a lot for people who have had a gastric bypass?

We do. I still see some patients who have had gastric bypass surgeries or any other bariatric surgeries who absorb oral iron in smaller amounts. They will get some slight improvement in their iron levels with oral iron administration, but you already have a reduced absorption generally, and they are probably 50% the absorption of a normal individual. Over time, they just generally decline their levels over months to a year and then require IV iron every year for a couple of years. That is pretty common for those gastric bypass patients.

How quickly do people feel better after the infusion? How long? We can talk about oral iron, which can take a couple of months, especially if it is severe. For IV iron, how fast do people feel those effects, and you see the improvement in labs?

The improvement in the iron levels is immediate. If you check them in a week, the levels will probably be reading at a high level. The iron levels improve first, and then gradually, your body is using that iron to produce more red blood cells. Symptom improvement is usually within about a week or two, and then they will start to have that initial surge of energy. It is not going to be to the fullest extent of improvement until probably about a month later.

That is when most patients feel the maximum benefit of IV iron. Within a week or two, they will notice some subtle improvements in that energy. Patients will say, "I have more exercise tolerance. I'm able to do more. I'm not falling asleep on the couch," things like that. The symptoms, such as the headaches, restless legs, trouble sleeping, and palpitations, those things usually improve rapidly within weeks.

In terms of risks, what would you say are the biggest risks that patients should know about with IV iron?

The main risk that we advise patients about is allergic reactions. Allergic reactions, if you read the literature, are variable, and they are variable between the different formulations of IV iron. Iron dextran, which has been around probably the longest, tends to have the highest rate of reactions, but the newer formulations of iron dextran actually probably have close to the same risk as the older formulations.

Tweet: The main risk we counsel patients about is allergic reactions, which can vary significantly depending on the specific IV iron formulation used.

They have modified the iron dextran products to make them at least close to the risk of having an allergic reaction as the newer formulations like iron sucrose, which is Venofer, and ferric carboxymaltose, which is Injectafer. We estimate the risk of an allergic reaction to be about one in 1,000 patients treated. It might even be less than that, but somewhere in that range. The patients at higher risk are those who have previously had allergic reactions or even those who have a laundry list of medication allergies. We tell them to just be more vigilant and know that they might have a higher rate of reactions.

Would it decrease if you have had IV iron in the past and you did not have a reaction, or is it still an equal risk, even if you have had it before and did not react?

If a patient had the same formulation of IV iron in the past and they were getting it a second, third, or fourth time, it is very uncommon for them to have an allergic reaction on a subsequent dose. If it is a different formulation, it all depends, because I have had patients react to iron dextran and then have no reaction to Venofer or Injectafer. I have had a patient or two react to Injectafer, and they did okay with the other options. If it is the same iron formulation on a subsequent dose, we do not worry about allergic reactions. If you go to a different formulation, the risk is still there.

What about dosing? If somebody reacted to a higher dose, or do you ever try the same formulation at a lower dose, or not really? You just kind of skip it, and you think the risk is the same?

It is not dose-dependent. There can be a reaction that is dose-dependent, but it is not a hypersensitivity reaction. When we talk about allergic reactions, we are talking about actually hypersensitivity, like you are mounting an allergic response to the sugar component of the iron, not the iron molecule itself. It is kind of what it is bound to, what it is mixed in. The reactions that tend to occur with a higher dosage of IV iron are infusion reactions.

It is more of the free iron that is in your circulation all at once that your body is not used to, and you kind of mount a systemic response to that. That could mean you feel achy, you feel like you have the flu, your joints hurt, you feel run down, you feel more tired after the infusion, which is not what we want patients to feel, but they can. Those would be more common with a higher dose, but allergic reactions and hypersensitive reactions are independent of dose. 

If people have those reactions, then the next time you would probably just decrease the dose, and they could stay on the same formulary.

Correct, and one of the examples of that is Venofer, which we use in the hospital a lot, which is iron sucrose. If you use the 300-milligram dose compared to the 200-milligram dose, you will see more reactions like that. You would not think that 100 milligrams makes a difference, but it does.

That is good to know, very interesting. Those would probably be the big things for iron. For the next topic, I was going to maybe talk about B12 deficiency in terms of anemia. I guess maybe if we started off with B12, how does it even affect blood cell production, and how does it play a role in anemia?

Vitamin B12 is another vitamin that is very important for blood production. It is important for amino acid production and for cellular function. It is not only the blood cells that require B12, but also many other cellular functions and even protein production. When we evaluate a patient for anemia, one of the labs that we commonly order is a vitamin B12 level. I know we are going to get folic acid or folate deficiency as well, but that is another common vitamin deficiency that can have a presentation of anemia.

We need to do the workup appropriately for both of those diagnoses. Just because a patient is vitamin B12 deficient does not mean that they are folate deficient, but sometimes those two vitamin deficiencies can go together. It just depends on what the underlying cause is. Getting back to B12, when someone is B12 deficient, it usually causes the red blood cells to swell in size or become larger. That is just because of how the DNA synthesis inside the blood cells becomes irregular.

The immature, newer red blood cells just do not form normally because of the deficiency in the vitamin, and you get larger blood cells. When we look at a complete blood count, and we see a patient is anemic, if we see those red blood cells are larger or the volume is bigger in size, it points towards vitamin B12 deficiency or sometimes even folate deficiency. That is one of the alerts that help make our differential diagnosis.

Even just regular labs, if you see someone is anemic, you could be like, "Wait, iron deficiency might be less the cause. Maybe it's more B12 or folic acid," and then you can test it specifically, which is great.

You can, correct.

What would you say is the most common cause for B12 deficiency, or who would be more at risk? 

Common Causes For Vitamin B12 Deficiency

Getting back to iron deficiency, when we talked about gastrointestinal conditions, chronic diseases, if a patient has chronic malabsorption from a prior gastric surgery, whether that is gastric bypass, or they had a portion of their small bowel resected, it could lead to impaired absorption of vitamin B12. That is one of the things we ask patients about. What kind of prior surgeries they had. You think of absorption as being a primary issue. Another common reason for vitamin B12 deficiency would be diet, right?

A patient has a vegan diet, and we know vitamin B12 is something that we require in our diet or to absorb from our diet, and it comes from animal products. Eating meat or eggs, and milk are other sources of vitamin B12. If you have a patient who has a vegan diet or a restrictive diet, they could certainly just be obtaining insufficient amounts from their diet. That could be leading to the deficiency. The deficiency usually takes months to years to develop, so it is not something that develops over a week to a month.

In a patient who has a restrictive diet, it probably took a good amount of time for them to become B12-deficient. Once they get to that critical deficiency, you are going to be seeing some striking abnormalities in their lab work. That is usually when patients' vitamin B12 levels are much less than 200 on the scale that we use to measure vitamin B12, and sometimes even down to a level in the double digits.

When I see a patient in the hospital with a vitamin B12 deficiency, and they have anemia or even other blood counts which are low due to vitamin B12, it is at a very low level. I am sure you have even seen a few patients who have a critical vitamin B12 deficiency, and their blood counts can be quite low and sometimes even transfusion-dependent when they are in the hospital.

Plus, you have all the other issues that come with low B12 because it functions in so many other parts of your body that are so necessary. It can be very dangerous. Are there any medications that people take that would decrease their absorption of B12? Are there common things that people take, or not really?

Some medications can affect vitamin B12. Off the top of my head, I think certain diabetic medications can potentially affect vitamin B12 absorption. I do not know if you have something in mind.

I was curious if any proton pump inhibitors or anything that affects the acid in the stomach affects the absorption, or not much.

Short-term use, not really, but long-term use. That is a good point. Long-term use of a proton pump inhibitor, such as Prilosec or Pepcid, can lead to malabsorption, where you are not going to absorb the B12 normally. The H2 blockers, again, Pepcid and Zantac, those types of medications, but it is really long-term use. I would not tell a patient not to take them for 2 to 4 weeks if they had symptoms that warranted treatment. Patients who are on them for years, yes, they are at risk. That is a good point.

I bet there is probably not any data on this, but I feel like everybody is on an SGLT2 inhibitor now, like Ozempic and all those. Do you guys see, because it is not like a gastric bypass, where part of your intestines are gone, so you have malabsorption. You just have decreased intake and slower emptying, but people are taking in less. Have you noticed if there has been an increase in anemia in terms of B12 deficiency and folic acid? I guess even iron.

Not so much, because we have quite a few patients on those medications. I really have not noticed signs of vitamin B12 or folate deficiency or even iron deficiency. The other patient that tends to develop vitamin B12 and folate deficiencies are alcoholics. It is not only those who are drinking a case of beer a day, but if you are drinking 3, 4, or 5 drinks a day, which some people think is not a lot, it could be enough. It could be enough to affect the absorption of those vitamins.

Again, some of the side effects or adverse effects of having low vitamin B12 and folate are affecting your other organ systems. It could be neuropsychiatric conditions. You can have mood alterations. You can feel like you're going crazy sometimes. You can have paresthesia, numbness, and tingling in your hands or feet. You can have weaknesses. In extreme cases, you can feel like you're becoming paralyzed, unable to move your limbs properly.

Tweet: Low vitamin B12 and folate can affect far more than your blood. They may cause mood changes, brain fog, numbness, tingling, weakness, and in severe cases, even paralysis or loss of limb function.

Those are extreme cases, but in glossitis, where you have tongue sensitivity or pain in your mouth, or it feels like something is burning in your mouth. That actually can be a sign of both iron deficiency and vitamin B12 deficiency. Some of these weird symptoms that people might complain about and just do not know what is causing them, it is worth working up some of these simple things, like these vitamin deficiencies. 

You do your labs, and they come back, and they are deficient in B12 and have anemia. When would you give them oral B12 versus doing an injection?

Again, a patient that you feel has a malabsorption of B12 due to a gastrointestinal abnormality that is not going to get better, so either that is a prior surgery, or they have a chronic condition where you think they are just not going to absorb B12 well. They are better candidates for injectable B12. We usually use the intramuscular injections at a thousand micrograms per dose. There are different ways to dose it in those patients.

Say you have a new diagnosis of vitamin B12 deficiency in the hospital. Sometimes we do the daily vitamin B12 for a week or so, and then we go to weekly, and then eventually you transition to monthly injections. Some of the protocols just say to start with weekly injections. As an outpatient, that is probably more convenient to just do weekly. After a month or two, you can transition to once-a-month or every four-week injections. Patients are usually able to inject themselves at home once they have some nursing education about how to administer it.

The other patients that are going to benefit from intramuscular injections are those with autoimmune reasons for vitamin B12 deficiency, something we call pernicious anemia. They can have autoantibodies that affect intrinsic factors, which is what helps vitamin B12 get absorbed in the small intestine. When you have an autoimmune condition that affects the absorption of vitamin B12, giving oral vitamin B12 may not be enough to allow for normal absorption.

There is some data, which, again, I do not have enough evidence to say one way or another whether this works. There are some reports from experts that say if you give a high enough dose of vitamin B12 orally, you can overcome that malabsorption, and you can have some passive diffusion of the vitamin B12, which does not require the normal intrinsic factor pathway of absorption. It is interesting that giving 2000, 3000, and 4000 micrograms, you might be able to overcome that resistance. 

I did not know that. I had not heard of that. I know I have also heard of sublinguals. Do you do that often?

I do. Usually, if you use a thousand micrograms or more, I think in someone who has normal absorption and does not have a reason why they are going to have impaired absorption of B12, I just give them pills, to be honest with you. The sublingual would be a good trial for that passive diffusion if you have a patient who you know has some reason for malabsorption, and you want to give them a trial to see if you can overcome that malabsorption. Just check the levels regularly to see that the level is coming up appropriately. There are a couple of other things you can check in the lab work to see that the vitamin B12 level is being corrected to appropriate levels.

How long does it usually take in terms of patients having improvement after starting oral B12 or doing IV?

The levels come up pretty rapidly, but some of those symptoms that could occur from having prolonged vitamin B12 deficiency, and that could be pancytopenia, meaning your white blood cell count, your red blood cell count, and your platelet count are all very low. I have had some patients with that. It usually takes weeks to a month or two to see those levels correcting back to the normal range. Those neuropsychiatric effects of having a vitamin B12 deficiency that we were talking about, the mood changes, the neurologic effects of the numbness, tingling, and sometimes weakness, could take months to get better. 

I have seen that it takes even longer than that. Especially in an older population or if it has been going on for a long time, it is wild how it can affect people. Iron IV always thinks of the allergic reaction. I do not really think of much when I think of B12 injections. 

I have not had a patient who had a reaction to vitamin B12, fortunately. It's just the way it's formulated. The iron is different.

Probably the biggest side effect from that would be just making sure that it's a clean area and keeping it sterile, I guess. Nothing jumps out to me, at least when I think of those injections. Interesting. The next one would be folic acid. We talked about it a little bit, about how it differs from B12 deficiency, but how folate affects anemia, and how it is a little bit different.

Folate Deficiency Affects And Treatment

Affects it similarly in terms of when we look at a complete blood count, we tend to look at the size of the red blood cells when we do an anemia evaluation. That can point us in the right direction for what diagnosis we are going to come up with. The folate deficiency also leads to macrocytic anemia, so the cells are larger in size. It is affecting a lot of different cellular processes in terms of folate or folic acid. Folic acid is actually what we give as a synthetic replacement for the folate that we get in our system from dietary intake. When we say folic acid, we mean supplementation.

Tweet: Folic acid is the synthetic form of folate, used in supplements, while folate is the natural form obtained from our diet.

Folate we get from our diets. That could be vegetables, that could be foods that are fortified with folate. A lot of foods now are fortified so that deficiency is less common than it used to be, back before foods included a high amount of folate. Patients again have absorption issues, gastrointestinal tract malformations, or surgeries or conditions that can affect absorption. Alcoholics, again, we worry about folate deficiency. Patients who have conditions with high cell turnover, such as skin or blood disorders.

Patients with sickle cell anemia, who have chronic hemolysis, and other conditions, lead to chronic hemolysis, which is the breakdown of blood cells. You utilize the folate at a higher rate than you are intaking. You end up becoming deficient. The skin turnover. Patients who have chronic skin conditions, where they have a really high rate of turnover of skin cells, can over time lead to folate deficiency if you are not replacing it with an adequate amount. They kind of reference that eczema can be one of the causes.

You do not really have that in your differential when you think about what can lead to the folate deficiency. Replacement of folate deficiency is easier than B12 because we rarely give injections. We almost always put patients on oral supplementation who come back folate-deficient. There is really no good evidence to say the exact amount of replacement for any particular deficiency. In the literature, it ranges from 1 mg to 5 milligrams a day. I tend to pick something in between, 2 mg or 3 mg initially, and then eventually you get a patient onto one milligram of folate a day after a few weeks on the higher dose.

You are just tracking the levels and making sure that symptoms are improving, anemia is improving, and your patient is getting better. You are trying to counsel patients to avoid alcohol. “If your alcoholic who might be chronically folate deficient, try to counsel them on reduced intake and taking their folate supplement, and then anything else that you think might be contributing to either decreased intake of folate or the absorption, such as those proton pump inhibitors, those acid-blocking drugs.” You will counsel the patient on stopping those or switching to something different. 

I have not given much IV. The scenarios that jump to my mind are like for patients who are really sick in pregnancy, and have hyperemesis gravidarum, and they get hospitalized, and it is so bad that I am seeing them in the hospital. Folic acid is so important, not just for anemia in that scenario. It is also important for the baby in terms of preventing neural tube defects. That is a scenario in which I have given the IV folic acid. It is like you said, it is not very common. Most of the time, I am able to just give oral folic acid. Some alcoholics have really bad pancreatitis and are throwing up, and are not able to keep down much oral. Do you find that for gastric bypass, they need the IV or not? Usually, the oral works for them? 

Usually, the oral works for them. I rarely encounter a patient who remains fully deficient with gastric bypass, so as long as they are adherent to the replacement.

It does help if you take the medicine.

Yeah, it does. It is hard. Even when I have had to take a medicine or two, it is hard to take them every day. You forget. People forget sometimes.

Now you do, and I do not think it is quite as common as iron is in terms of being hard on the stomach. Everybody has different sensitivity levels. We went over how there can be an overlap and how, sometimes, in the labs, you can see a difference between iron deficiency causing anemia versus B12 and folic acid. How often do you see an overlap in terms of your deficiency with iron, folic acid, and B12?

I would say the times we see all three deficiencies would be more of a hospitalized patient or severely malnourished patients. Occasionally, you will see an outpatient alcoholic who has relatively mild deficiencies in all of those parameters, but it is more common in a hospitalized patient who may have malnutrition from anything, and just very poor PO intake, or they have a chronic medical condition.

Say they have inflammatory bowel disease, or they have a history of many gastric or intestinal surgeries, and they came in with some complications, and they just have not had adequate intake. Those are probably the patients who have the trio of deficiencies. If I see it in the outpatient setting, it is probably milder, and it is probably not affecting their blood counts as severely. That makes sense.

Let us say a person had some of those vague symptoms, and they went to their primary care doctor, and they got diagnosed with anemia, whether it was iron deficiency anemia or B12. When should they ask to be referred to a hematologist and see someone like you?

Different primary care physicians have different comfort levels in how they manage all of these conditions. Vitamin B12 and folate deficiencies are fairly straightforward to manage, and I see a lot of primary care providers managing them appropriately. We see many more iron-deficient patients for new consults to consider IV iron formulations for treatment because most primary care providers cannot set them up for infusions in their clinics.

They send them to ours, and it is when a patient either has a poor tolerance of oral iron or just is not obtaining the response they want with the oral iron. They come to us to say, "Can we set up these IV iron infusions to improve symptoms, improve my levels?" I end up monitoring them along with their primary care physician over the years.

We talked about it a little bit before, but how important it is to find the actual underlying cause, especially iron deficiency anemia.

Importance Of Finding The Underlying Cause

Extremely important. I always reinforce that. I know you do too. When you see an iron-deficient patient, you want to teach them that, "We will give you iron replacement, either oral or IV iron, but this is patching a problem which we need to investigate." The investigation really requires a gastroenterologist to be on board and determine if there is a malabsorption of oral iron due to a medical condition, which is diagnosed or undiagnosed, or a bleeding source, is it a blood vessel in the gastrointestinal tract that is bleeding? Is it a tumour in the gastrointestinal tract that is bleeding?

Tweet: When you see a patient with iron deficiency, you should explain: “We will replace the iron—either orally or intravenously—but this is only addressing the symptom, and we still need to investigate the underlying cause.”

I usually am able to ask the patient enough questions to decide if they have decreased dietary intake. That is easy to tease out if maybe they are just not getting enough in their diet, or if they are chronic blood donors, and we can kind of figure that out in the clinic. I will not send those patients for the GI workup. But if a patient is not chronically donating blood, if they are not restricting their diet of iron, then we need a GI consultation to thoroughly investigate for either a malabsorption or maybe an occult blood loss somewhere in the gastrointestinal tract.

Especially with how colon cancer is on the rise, I think a lot of times people do not realize that even something like that can end up having this bleeding, and so people need to get a full investigation and not just put a bandage on it. Sometimes, just giving the iron, you are not looking into what is causing that iron loss. It’s very important.

To your point, given that we hear so much in the news and clinics, we see it as well that a lot more young patients are being diagnosed with colorectal cancers. It is not ignoring the symptoms of blood loss in your stool. When you have bright red blood in your stool, dark blood in your stool or your stools look black, and you do not know why, get evaluated. Do not chalk it up to hemorrhoids. Do not chalk it up to what you think you know it is.

You're a little constipated, or all the other things that I have heard patients tell me.

Bleeding is abnormal.

It needs to be investigated for sure. 

It is easy nowadays to do it. The gastroenterologists are good now. They can get patients in quickly, do it safely, and have a low rate of complications. Both you and I really encourage patients to do that.

It is very important. What are the long-term consequences if anemia is not treated? The worst, obviously, is death, as people know. You can die from severe anemia, but there are so many other issues, too, that can happen.

Long-Term Consequences If Anemia Is Not Treated

Most young people are not going to die from anemia, even if it is severe. You are going to probably show up to the ER eventually with a hemoglobin of 5, 6, or 7, and receive a blood transfusion and the appropriate treatment of your anemia. But it does put your body under a lot of strain, a lot of stress. It can stress your heart. You can cause other medical problems by having long-standing severe anemia. You can stress your heart to the point of potentially developing arrhythmias and decreased function of your heart.

It can probably lead to a tachyarrhythmia that leads to your heart function reducing over time if it is long-standing enough. Kidney malfunction. You can end up with acute kidney injury due to poor perfusion because you are not getting enough oxygen delivery. Especially if you are dehydrated on top of the anemia, your kidneys are very sensitive to the fluid balance in your system, the blood pressure balance, and the delivery of oxygen. Just a general function. You are not going to be able to function well on a daily basis with hemoglobin at seven or below.

Your whole body is having to work overtime.

You are not going to be able to think clearly or do your job appropriately. We encourage patients, if you are feeling fatigued and you do not know why, it is simple to go in with your primary care and get a blood test.

It is an easy workup to see and get it checked out. You can try to find the underlying cause. It is very important. My son, he was a little bit anemic when he was a toddler. The finger sticks that they do to test are not the most accurate, but I knew that he was because he was having pica syndrome, craving dirt. For him, it was chalk. He wanted to eat all the chalk, all the sand, and all the dirt. For me, when I was starting to get a little bit anemic in my pregnancy, it was the ice.

That is something else for adults. It seems more common that they crave ice than chalk or dirt.

I wonder if it is like, you know, in your head that you are not supposed to crave dirt, like maybe that is why you eat ice chips, because it is more normal. I do not know.

I am sure. You look crazy eating dirt all the time. That is a good point. Some patients come into the clinic, and they kind of have this light bulb, "Craving ice is a sign of iron deficiency." It is like, it is. For all of our audiences, if you are craving ice all the time, get your blood checked.

Yes, exactly. Thanks so much. This is an awesome episode with so much good information. I know our audiences learned a lot with that. As always, this episode is not intended as medical advice. This is for educational purposes only. This was so great. I enjoyed it so much.

Thank you so much for having me. It was so much fun. I enjoyed talking with you. We will have to pick another very interesting topic for the future.

Yes, absolutely. Everybody check out his show, The Danny & Rick Show, too.

Thank you so much. Thanks for plugging the show. We will talk soon.

Sounds good. Thanks. Bye.

Thanks. Bye.

Important Links

• Dr. Daniel Kobrinski
• The Rick & Danny Show on YouTube
• The Rick & Danny Show on Apple Podcast
• The Rick & Danny Show on Instagram

About Dr. Daniel Kobrinski

Dr. Daniel Kobrinski is board-certified in hematology, medical oncology, and internal medicine and practices at our Beaches location. Dr. Kobrinski earned his Doctor of Osteopathic Medicine from Nova Southeastern University in Davie, Florida, before moving on to complete both his residency and fellowship at Loyola University Medical Center in Maywood, Illinois.

The prospect of being in a field of medicine that is so rapidly evolving, combined with his love of building connections with patients and their families, are the two biggest reasons Dr. Kobrinski chose hematology/oncology. “I strive to make a positive difference, no matter how big or small,” he says. “Being able to provide patients with the best treatment options for their diseases to help meet their goals and spend more quality time with their family– there is no better feeling.”

His personal connection to cancer significantly influenced his love of patient care. During his first year of his hematology/oncology fellowship program, Dr. Kobrinski's mother was diagnosed with Stage IV lung cancer. “My mom fought courageously, but she unfortunately passed away one year after being diagnosed,” he explains. “Her love and endless support has helped me so much, not only as a parent, but as a physician.”

In order to be closer to their family in Orlando, Dr. Kobrinski and his wife chose to settle in North Florida to raise their children. When he found CSNF, he was proud to join a “well-respected and professional group physicians, committed to patient care” and was instantly proud to join the team.

An avid drummer since elementary school, Dr. Kobrinski enjoys teaching his children about music and spending time with them and his wife. When he has the chance, he enjoys basketball and golf. He also enjoys educating through podcasts and is one of the hosts of the Rick & Danny Show.