The Progression of Iron Deficiency

Often, a person’s anemia is found through routine screening at the doctor’s office or after they begin to experience the symptoms of iron deficiency, commonly fatigue. Iron deficiency anemia doesn’t just happen though, but rather progresses through different stages that take it from iron depletion to full-blown anemia.

Simply put, iron deficiency depicts having less than adequate iron levels in the body; this can occur from a number of conditions, mainly due to blood loss, or impaired absorption. Iron deficiency anemia presents with a low red blood cell count or inadequate hemoglobin, which is due to insufficient iron.

Red blood cells (erythrocytes) carry oxygen throughout the body via their hemoglobin. Hemoglobin binds to oxygen and enables the red blood cells to supply oxygenated blood throughout the body. Iron is necessary to produce hemoglobin. Thus, when the body lacks iron, the result is altered production of hemoglobin.

Here are a few facts:

  • On average, men have 5.2 million red blood cells per cubic millimeter of blood and women have 4.7 million red blood cells;
  • Each red blood cell contains 280 million hemoglobin molecules;
  • Red blood cell production (erythropoiesis) primarily occurs in the bone marrow;
  • The lifespan of a red blood cell is 90 to 120 days; when old red blood cells are broken down for removal by the liver and the spleen, iron is returned to the bone marrow to make new cells;
  • The extra iron in the body is stored in the liver and bone marrow for hemoglobin synthesis.

Now that we understand a bit of what is happening in the body, the following are the three stages of iron deficiency to help give you a clearer understanding of how iron deficiency progresses.

First Stage: Iron Depletion

First, an insufficient supply of iron causes the iron stored in the liver to be depleted. Generally, this stage goes undetected – typically there are no symptoms and no overt effect on red blood cell production (erythropoiesis) – escaping detection during hemoglobin or hematocrit screening as these levels are usually normal when tested.

This stage is often characterized by low serum ferritin levels, indicating decreased iron storage in the liver. Blood tests will show a decrease in ferritin levels, the normal range being 20 – 300 nanograms per milliliter (ng/mL); however it is possible that the patient becomes symptomatic with ferritin levels less than 50 ng/mL.

During this stage, iron storage is significantly reduced, or sometimes absent, and continued iron store depletion leads to the second stage.

Second Stage: Iron Deficiency

Second, iron deficiency develops and begins to affect hemoglobin production, and iron stores in the bone marrow are substantially reduced. Though this is not always the case, in what I consider to be the “triad of symptoms” related to iron deficiency, patients may experience chronic fatigue, difficulty concentrating, and irritability.

This stage is characterized by abnormalities in certain iron parameters. While hemoglobin or hematocrit levels may be reduced, iron deficiency may not be detectable using the normal cut off values. Decreased ferritin levels are typically present and can be detected, but there is also increased capacity of binding and transporting iron; this signifies your body being prepared should iron become available.

The tests most frequently used to assess patients suspected of having iron deficiency include total iron-binding capacity (TIBC) and a serum iron test. Combined, these two tests are used to evaluate the transferrin saturation, a useful indicator of iron status. About 20% – 40% of available transferrin sites are used to transport iron in a healthy patient. In a patient with iron deficiency, iron levels are low but the TIBC will be increased, which results in a very low transferrin saturation.

Final Stage: Iron Deficiency Anemia

In this advanced stage, due to chronic insufficient iron in the body, the iron stores have depleted to a point where they can no longer produce the hemoglobin needed to make enough red blood cells. As the body becomes increasingly deficient in iron, aneTriad of Symptoms Related to Iron Deficiencymia worsens and symptoms intensify. This stage is characterized by a significant reduction in hemoglobin levels. As such, blood tests at this stage will show considerably low hemoglobin and hematocrit levels.

As you can see, early detection of iron deficiency isn’t easy. Symptoms generally associated with the first stage (and sometimes even the second stage) often mimic other conditions or are brushed off as just simply feeling tired. Further, by the time changes in hemoglobin and hematocrit can be detected through blood screening, a person’s iron stores have already been significantly depleted and are in need of replenishment to avoid further symptoms and complications.

I will leave you with this: If you suspect iron deficiency or anemia, it is extremely important to be proactive and talk with your primary healthcare provider!

Content and advice provided on The Iron Maiden is for information purposes only and should not serve as a substitute for a licensed health care provider, who is knowledgeable about an individual’s unique health care needs

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15 thoughts on “The Progression of Iron Deficiency

  1. Leona, RN & Blood Specialist says:

    Good question Nora!

    When I am assessing a patient for iron deficiency in the absence of anemia (Stage 1 and Stage 2), I look at both an iron panel (TIBC, Serum Iron, Unsaturated IBC and Transferrin % SAT). Some factors can falsely increase the Ferritin level (infection and inflammatory processes such as rheumatoid arthritis). Because of this, an iron panel is definitely the gold standard for diagnosing iron deficiency in the absence of anemia.

    If you are a member of an “at-risk” population group, discuss with your primary health care provider the need for base line blood work and frequency of follow-up. My “at-risk” patients are reviewed every six months minimally.


  2. Carol says:

    I am so happy to find this page.

    I have struggled with IDA due to heavy periods for five years. After a couple of operations the bleeding has improved somewhat from over 10 days or continuous to 2 heavy days. I estimate that I am still losing more than at least 120 ml per period ( I have seen research that more than 80ml is considered heavy or mennorghia. I have not stopped taking Palafer 300mg x 2. A test in January came to 125 for HB and 37 for ferritin. Last september 2014 I had 115 for HB and 27 for ferritin.

    At one point my GP sent me for iron infusions at hospital but the doctors at the emergency did not consider the situation serious enough and plus there was a shortage of iron at that time and as I was absorbing iron pills well, they felt I would be fine with that.

    I am just tired of popping the pills and watching my levels crawl up so slowly.I do not have kids yet and would like to so my doctor will not consider a drastic operation at this point. Besides my research I found out that anemia can be a cause of infertility which is my other problem.

    My question is how can get to be considered for iv iron at this stage when they did not consider me when my levels were much lower? Can I go to a naturopath? I live in Montreal.

    • Leona, RN & Blood Specialist says:

      Hi Carol,

      You have certainly had your struggles with iron deficiency! One of the biggest struggles I have in getting patients to timely and appropriate treatment is getting physicians to understand that iron deficiency exists and can be debilitating in the absence of anemia. My common lab values state that a normal Ferritin level is 20-300 mg, but we know that patients can be symptomatic of iron deficiency once this level drops below 50. I also know from my practice that once in the 20 range, Ferritin stores are difficult to replete with oral iron alone. In consultation with a clinical haematologist, I typically treat Ferritin levels this low with intravenous iron. The use of intravenous iron in these cases is strictly at the discretion of the medical practitioner. You may have more success with a referral to a clinical haematologist versed in this issue than with your local emergency. You can learn more about this treatment option in my article about IV iron.

      I would also like to encourage you to consider an oral iron that may offer more bioavailable elemental iron, giving you more easily absorbed elemental iron such as Polysaccharide-Iron Complex (such as FeraMAX 150) or Heme Polypeptide (such as Proferrin). Both of these irons are outlined in my article on available iron supplements in Canada, and should help spark a discussion between you and your personal health care provider.


  3. Diana LaTour says:

    Hi Mary Lou,

    I have had low iron levels off and on for many years.3 months ago bloodwork showed my iron level to be at 60…my GP suggested Ferramax which I have taken once a day and my follow up level(tested a week ago) showed it had dropped to 40. She has ordered more blood work to investigate further(red blood cell count etc.) in a couple weeks time but in the meantime she suggested starting to take 2 a day rather than one. I take Synthyroid so must take Iron away from it so I take it at bedtime…will I be able to absorb 2 pills at once effectively? I also have chronic Adrenal Fatigue…(not sure if thats relevant). Any thoughts on why my levels would drop rather than increase after 3 months of supplementation? Signed, exhausted and confused. Thank you!

    • Leona, RN & Blood Specialist says:

      Hi Diana,

      Wow! What a great question! It gives me a chance to remind readers that Thyroid Replacement meds need to be taken separately from iron supplements. Look for an article to explain why soon. A minimum of four hours on either side of each medication is recommended. Certainly you are going to want to continue taking your synthroid first thing in the morning to give you the energy you need to face your day. Unfortunately, our body can only digest and absorb so much iron at one time, and taking two FeraMAX at one time means most of the second one is being “flushed”.

      Since only a four hour window is required, consider taking one at noon and the second one before bed. You can increase the bioavailability and thus absorption of your FeraMAX by opening the capsule and mixing it with a warm beverage or soft food. It is odourless and tasteless, but will make whatever it is mixed with darker in colour.

  4. Arlene Ricker says:

    Hi Leona,
    I appreciate your website so much! I am almost 55 and healthy but started getting sooo out of breath with any exertion that I thought something was wrong with my heart. After tests, they found my Ferritin level to be at 3! After six months of one FeraMAX a day it hasn’t gone higher than 8 and dropped again to 5. Since my hemoglobin has gone up to normal they aren’t that concerned about my low Ferritin. I am still very short of breath with exertion. I have been taking 2 FeraMAX a day for a month now to see if that helps. I will try opening the capsule like you suggest , but will that cause staining of my teeth?

    • Leona, RN & Blood Specialist says:

      Hi Arlene,

      First, no, taking FeraMAX out of the capsule will not stain your teeth. It is tasteless and odourless; however, when added to food/liquid, they may appear darker in colour. The contents of an open capsule should be added to warm fluids to be completely dissolved. It can be added to soft foods although it may give these soft food a “gritty texture”.

      Anecdotally, a very important point I would like to make , it is difficult (if not impossible) to replete iron stores with oral iron alone once the ferritin value is less than 20. At the levels you are quoting, I would be recommending IV iron for you.


  5. Wendy says:

    My levels just came back with ferratin at 3, iron at 3 and hemoglobin at 6.5. I somewhat afraid of the infusions (if my insurance will cover it), but my primary is giving me a referral. Also I am seeing my OB regarding procedures to lessen the flow of my period this week. I feel like its going to take forever to get back to normal.


      Hi Wendy,

      I am sorry that your lab values had to drop so low before getting to definitive treatment. Unfortunately, you did not become so depleted overnight so the road to recovery will also take some time. The important thing to remember is that you are on the road to recovery and the use of intravenous iron will help speed up the trip.

      Keep me informed on your IV iron experience…I care!

  6. Sarah says:

    Hi there,
    I’m wondering if low iron, and the resulting side effects, are reason enough to take time off work.
    My latest labs show ferritin of 5 and hgb of 118.
    My gyn is arranging iv iron, but they can’t get me in for a month. He said that for him to write me off my hgb would have to be 90 or lower. Isn’t non-existent iron enough?
    He told me to f/u with my GP, which I will on Monday. I have no idea how I can work when I’m super irritable and just want to nap all day.
    Any experience of people being unable to work due to low ferritin?

  7. Karla says:

    Hi Leona,
    I have been browsing the website here and I really appreciate all the information. My Hemoglobin is at 119 and my ferritin is at 8. I have been taking iron supplements for the last year, and they have not entirely been effective. I asked my doctor about iron infusions and he replied to me saying that my iron levels are not critically low enough to warrant iron infusions. The iron supplements also wreak havoc on my digestive system. From what I have read here, it seems that I would be a candidate for the infusions. What is with my doctor? Is he just uneducated in this area or is it a case of him trying to save the system some money? I’m finding it frustrating. It would be great to feel good again. Thanks

    • The Iron Maiden says:

      Hi Karla,

      Unfortunately, iron deficiency and its symptoms often remain under the radar. Many doctors believe if you are not anemic you’re not iron deficient, this, however, could not be further from the truth.

      In the article “The Progression of Iron Deficiency” you see that you can be debilitated by the symptoms of Stage One and Stage Two iron deficiency for years, in some cases, before you are finally anemic and your doctor agrees to treat.

      The second piece of valuable information is that anecdotally once your ferritin drops below 20 it is difficult if not impossible to replenish your iron stores with oral iron alone.

      So long answer short. Yes, you are most likely a good candidate for iv iron. You need to speak with your doctor and request a referral to a Benign Clinical Haematologist. I recommend a Benign over and Oncology Clinical Haematologist as they tend to be more aggressive with the treatment of iron deficiency.

      Finally, you talk about the iron you are taking “doing a number” on your GI tract. From this, I assume you are taking an iron salt or vegetable based iron. These irons need to be converted from the type of iron they are to the type of iron our body likes to absorb. Taken under optimum conditions as little as 8 % of these supplements are converted for potential absorption. The remainder passes through your gut undigested resulting in the symptoms commonly associated with oral iron therapy (nausea, indigestion, black tarry caustic constipated stool and abdominal cramping). There are 2 oral iron supplements available that significantly reduce, if not virtually eliminate, these symptoms. Consider switching to a polysaccharide iron complex or a Heme Polypeptide Iron. Talk to your pharmacist about these 2 classes. The per pill cost is a bit higher, but because you need fewer per day the daily cost of therapy is more in line. I also understand that for many price is a very significant issue, however; paying a bit more to absorb more with fewer side effects is a very important fact to think about.

      I wish you luck in your journey back to wellness, a journey that begins with self-advocacy.

      Let us know how things work out…I’d be interested in knowing.

      All of the iron maiden articles are printer friendly. Maybe you’d like to take a few to show your health care provider, especially the symptoms checker and the article on the progression of iron deficiency.


  8. Kathy says:

    I recently had my trio appointment at Humber and the nurse told me my iron was low and gave me a copy of my blood test results. My iron was 5.6 (normal range 7.0-30.0) and my ferritin was 33 (normal 20-300). She told me to start taking Feramax 150 at night with 500 mg of vitamin C. I just wanted to check that this would be enough. Obviously I have not had the surgery yet so how long do you think it would take to bring my levels up before the surgery. I am on track for a September surgery date if all goes well.

    • The Iron Maiden says:

      HI Kathy,

      I apologize for the delay in reply. Congratulations on your journey to health and well-being. You are in for a roller coaster ride. I am so very excited for you. I am also happy to read Humber is recommending FeraMAX.

      Unfortunately, it is beyond my scope of practice to speak of dosage information in an open forum. Please watch your inbox for a message containing my personal contact information.

      Good luck in your journey, I am busy polishing a spot for you on the bench.


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