Clinical Consequences of Iron Deficiency (Part Eight)

It should be noted that ferritin concentrations increase in the acute phase of the inflammatory response (infectious or not). When there is an inflammatory disease (infectious or non-infectious such as RA, cancer, etc.), the value of ferritin (as an acute phase protein of inflammation) is higher, but always less than 50-60 μg/l (in this case, sideremia measurement helps, which when low is certain that there is an iron deficiency).

The value of ferritin is the most definitive (91% of cases) in diagnosing iron-deficiency anemia, among all other tests for iron deficiency. Given that ferritinemia is elevated in any acute inflammatory process, iron deficiency is potentially undervalued in developing countries, where the prevalence of inflammation is high.

Sideremia indicates the amount of circulating iron in plasma bound to transferrin. It has diagnostic value for Iron Deficiency Anemia only when it is low. If it is normal or elevated, it has no value. It may actually be low, but if the patient has consumed food containing iron that is absorbed, has taken iron supplements or therapeutic preparations, or from the metal part of the syringe itself, it appears normal.

Ferritinemia is not affected by one or several intakes of iron through food, supplements, or therapeutic preparations, as at least 6 weeks are needed to correct it (if the cause is removed, if it persists, it takes longer) with a therapeutic dose of iron medication (180-200 mg elemental iron).

Example of the Laboratory of Hypochromic, Microcytic Anemia

CBCResultsNorms
RBC (x1012/L)4.24.2-5.4
Hgb (g/dL)10.611.5-15.5
Hct 34.9%38%-47%
MCV (mm3)77.080-96
MCHC30.4%32-36%

Rules of Three:

  1. RBC X 3 = Hemoglobin
  2. Hemoglobin X 3 = Hematocrit

For practical purposes, the Rule of Three for the Red Series (erythrocyte) can be used. It should be stressed that this is valuable for normochromic anemias. Normally, if you multiply the initial values of the number of normochromic erythrocytes by 3, you get Hb. For example, if Erythrocytes are 4.5 million/mm3 (4.5 x 106/mm3 or 4.5 x 1012/L) and Hb will be 4.5 x 3 = 13.5 gr/dL if erythrocytes are normochromic, that is, filled to their maximum with Hb. If you multiply the initial values of erythrocytes by 9 or the Hb value by 3, hematocrit will result; 4.5 x 9 or 13.5 x 3 = 40.5 % if erythrocytes are normochromic, that is filled to their maximum with Hb. If you have 4.5 million/mm3 erythrocytes, but only 10 gr/dl Hb then you can deduce that the patient has hypochromia, because if it were normochromic it should have had 13.5 gr/dL Hb.

You may have erythrocytes within normal values, but being smaller in size (necessarily will have hypochromia because Hb measured is always only within the erythrocyte) and hematocrit will be lower because the volume occupied by erythrocytes (despite being in normal number) will be smaller.

Treatment

Treatment with oral iron preparations is ideal for correcting the clinical and laboratory presentations of Iron Deficiency Anemia and replenishing iron stores, as it uses the body's normal mechanisms. The short passage in the G-I tract limits iron absorption. Only 2-3 mg of elemental iron is absorbed for every 50-100 mg of iron present in the intestinal lumen.

Replenishing 2000 mg of iron deficit may require more than 1 year of therapy. Many patients fail to follow such a long medical regimen. Therapeutic failures are frequent in the oral treatment of iron deficiency and Iron Deficiency Anemia. In these cases, parenteral treatment (I/V or I/M) is used, which requires accurate calculation of the correction of anemia and replenishment of stores (specified formulas) or more effectively (but not advisable with blood transfusion, knowing that 400 ml of blood contains 200 mg of elemental iron). In parenteral treatment, physiological loops of iron absorption are bypassed, as it is directly entered into circulation, where it will bind to transferrin.

It should be stressed that the use of blood transfusions in iron deficiency anemia is not recommended, because it is a chronic anemia (it takes 4 months for the normal erythrocyte population to be completely replaced with the hypochromic, microcytic ferrodeficient population since each erythrocyte lives for an average of 120 days, 4 months) and as such is well tolerated by patients even in moderate or deep levels of it.

Treatment of Iron Deficiency
  1. If possible, find and remove the cause that depletes the iron stores.
  2. Treatment with iron preparations to correct iron deficiency, its stores, and maintaining them adequately.

Iron Deficiency Anemia is not a true disease, it is a consequence of the cause. Doctors and patients should aim to find and eliminate the cause if possible, iron deficiency anemia is corrected.

In most cases in practice, at least in Albania, the patient is told to consume foods that are rich in iron (liver and red wine are almost always prescribed). They contain iron, but not in the quantity needed to correct the deficiency (therapeutic dose of iron is 180 – 200 mg elemental iron).

If you were to treat iron deficiency with food, it would require 4.5 kg of meat/day for a minimum of 3 months in a row. Practically impossible, therefore therapeutic preparations per os (not just iron supplements that contain 15-20 mg elemental iron as needed by a person with normal iron stores) are preferred. The therapeutic iron preparation is assessed.

The assessment is not made by the size of the tablet, but by the content of elemental iron in it. For example, a Ferrous Sulfate tablet 300 mg has 60 mg elemental iron, meaning the patient needs to take 3 tablets a day (3 x 60 mg = 180 mg elemental iron). You may take more, but it won't be of any value, except it will irritate the Gastro-Intestinal Tract mucosa more. The body absorbs what it needs, the rest is eliminated through feces (which turn dark in color).

Although heme iron is better absorbed than inorganic iron, the quantity of heme iron in meat is actually quite small. In fact, an average (3-ounce) serving of steak provides only about 3 mg of iron. Provision of sufficient dietary iron to permit a maximal rate of recovery from iron-deficiency anemia might require a daily intake of at least 10 pounds of steak (4.535924 kg). For these and other reasons, medicinal iron is much superior to dietary iron in the therapy of iron deficiency

The most economical and effective treatment in the management of iron deficiency is the oral administration of ferrous sulfate salts. Ferrous sulfate is the most effective, better tolerated, and least expensive preparation. Currently, in our country, Ferrous sulfate is available in the form of Retafer which contains 100 mg elemental iron. The daily therapeutic (medicinal) dose of iron is 180-200 mg Fe elemental (iron metal). This means that two tablets are required per day.

There are also other Fe preparations which contain less Fe elemental (thus irritate the gastro-intestinal mucosa less), but in all cases, the daily therapeutic dose of iron of 180-200 mg Fe elemental must be taken. Iron is better absorbed when taken on an empty stomach, whereas when taken after food or together with it, iron absorption is reduced by 40-50%. But irritation of the G-I mucosa is common when iron is taken on an empty stomach.

The aim of the treatment is not only the rate of increase in Hb but also the patient's well-being. Therefore, it is advised for the patient to take the iron preparation in the middle of a meal or after it, because supporting the medication is more important than reducing iron absorption. Iron absorption increases when the preparation is taken in the presence of orange juice or lemon, meat, fish, Vitamin C, and is inhibited when taken in the presence of milk, tea, tetracycline, quinolones, methyldopa, calcium, and cereals. And the amount of food matters.

The larger the amount of food eaten, the better the iron preparation will be tolerated. It has also been observed that iron (its salts) are well tolerated when the dose is gradually increased until the full dose of the preparation is reached over a few days. If there is irritation of the gastro-intestinal mucosa and when the degree of anemia is mild and/or the cause is removed, the treatment of iron deficiency anemia can be done with a therapeutic dose of iron up to 100 mg/day. In this way, we decrease the speed of response to the treatment but increase tolerance to the medication.

If the patient does not tolerate Ferrous sulfate, other iron salts can be used: gluconate, fumarate (both compared with the effect of ferrous sulfate), lactate, succinate. Some of them are more expensive than Ferrous sulfate.

In some cases, correction of iron deficiency can be done by taking iron parenterally (intramuscularly or intravenously) which should be stressed is not only more costly than oral treatment but also carries the risk of a series of side effects (anaphylactic reactions, thrombophlebitis, tissue hardening, discoloration, etc.) and are preferred to be done in the presence of specialized centers.

The treatment usually continues for a minimum of 3 months (6 weeks to eliminate the clinical presentation of iron deficiency and 6 weeks to replenish the stores). But it may continue longer if the cause is not eliminated. Therefore, the aim of the treatment is not just to normalize the symptoms and signs of iron deficiency, normalization of the red blood cell count and hemoglobinemia, but to replenish the stores. Replenishment of stores is assessed with the normalization of ferritinemia.