In this article, we will discuss two types of microcystic anemia: Chronic disease/inflammation anemia and iron deficiency anemia. We will go in-depth into iron deficiency anemia and also discuss pharmacologic therapies used in the treatment of iron deficiency anemia.
Introduction to Microcytic Anemia
To determine whether it is microcytic, normocytic, or macrocytic anemia, we look at the mean corpuscular volume (MCV). If the MCV is less than 80, then it is considered microcytic anemia. If it’s between 80-100, then it is normocytic anemia. And if it is more than 100, it is macrocytic anemia.
In microcytic anemia, one of the most common etiology is iron deficiency. This is why iron studies should be completed to determine if it’s iron deficiency anemia or other types of anemia. The values that we should consider are serum ferritin and TIBC. A quick reminder, the normal value for serum ferritin is between 20-250 ng/mL for males and 10-150 ng/mL for females, and the normal value for TIBC are between 220-420 mcg/dL.
Another common type of microcytic anemia is chronic disease anemia. Both the anemia of chronic disease and anemia of iron deficiency will be discussed further in this article.
Other types of microcytic anemia are lead intoxication, thalassemia, and sideroblastic anemia.
Chronic Disease Anemia
This type of anemia develops over a long period of time from chronic disease. Some examples of chronic diseases that can lead to this are rheumatoid arthritis, systemic lupus erythematosus, gout, HIV, irritable bowel syndrome, heart failure, malignancies, and chronic inflammation.
The constant inflammation leads to the constant release of cytokines. Cytokines inhibit erythropoietin and red blood cell production. Chronic inflammation also releases hepcidin, which prevents the absorption of iron from the gut. The result of these two processes is that patients cannot make more red blood cells.
In these patients, their serum ferritin may be normal to high (not deficient), and their TIBC may be low.
Iron Deficiency Anemia (IDA)
This type of anemia develops after a prolonged iron deficiency. Most commonly this is due to a nutritional deficiency. The population that is most at risk are children, older adults, adolescent girls, pregnant females, and lactating females.
Iron is stored inside our body in the liver, bone marrow, spleen, and macrophages. Inside the macrophages, iron is stored as ferritin or hemosiderin. Hemosiderin functions to prevent iron absorption.
Because of this storage iron (ferritin) is a good lab value to look at to determine whether or not the patient is deficient. In the early stage, the serum iron and hemoglobin values may be normal and the serum ferritin is low. As the disease progresses, both serum iron and serum ferritin are low with normal hemoglobin values. The last stage is when serum iron, serum ferritin, and hemoglobin are all low.
In the earlier stages, the patients may be asymptomatic or fatigued. As the disease progresses, patients may present with glossal pain, smooth tongue, reduced salivary flow, pica (compulsive eating of non-food items), and pagophagia (compulsive eating of ice).
Serum iron may be low or normal. Ferritin may be down. Transferrin saturation may be low. TIBC may be high.
Daily Iron Requirement
- Infants: 11 mg
- Premenopausal women: 18 mg
- Pregnancy: 27 mg
- Adult men: 8 mg
Treatment Approach
The first step in the treatment is to correct the underlying cause or disease state. If a poor diet is the cause of iron deficiency, encourage the patient to consume foods with high iron content, such as animal liver, beef, spinach, beans, and fish.
The next step if the first step is not sufficient to replenish iron stores and normalize hemoglobin concentration is to utilize oral supplementation.
It is typically recommended that the patient takes 150-200 mg of elemental iron in 2-3 divided doses. There are multiple formulations of iron supplements. The different formulation contains different amount of elemental iron.
- Ferrous sulfate: 20% elemental iron | 325 mg for 65 mg elemental
- Ferrous gluconate: 12% elemental iron | 325 mg for 38 mg elemental
- Ferrous Fumarate: 33% elemental iron | 325 mg for 106 mg elemental
- Ferric Maltol: 30 mg for 30 mg elemental
- Ferric Citrate: 1 gram for 210 mg elemental
New studies have come out that suggest that lower dosing may be effective with fewer side effects. This may be because excess iron does not get absorbed. For example, ferrous sulfate 325 mg contains 65 mg of elemental iron and is recommended to be taken once daily or once every other day.
Key Counseling Points for Iron Supplementation
- Take at least 1 hour before meals if possible because iron absorption can be affected by foods
- If the patients cannot tolerate it, an iron supplement may be taken with food. Patients should avoid taking foods that decrease stomach acidity, such as milk.
- Acidity can increase iron absorption. Orange juice is a good option for this.
- Common side effects are dark feces, constipation, diarrhea, and GI issues.
Iron Supplement Drug Interaction
Because iron absorption can be affected by the pH of the stomach, any medication that interferes with the stomach’s pH should be avoided. These medications include antacids, calcium, magnesium, H2 blockers, PPI, and cholestyramine. Tetracycline antibiotics can form a complex with iron, which decreases the absorption of both antibiotics and iron.
Some medications can be affected by iron. These are levodopa, methyldopa, levothyroxine, mycophenolate, fluoroquinolones, and tetracyclines.
To MINIMIZE the interaction, iron supplement should be administered at least 2 hours before or 4 hours after these medications.
IV Formulations
IV formulations are indicated for patients who cannot sufficiently absorb iron from their guts (IBS or gastric bypass), are intolerant to orals, are CKD patients, or have malabsorption. These agents are typically administered at infusion centers. This is to help control the distribution of IV iron because if IV iron is infused too quickly, it can interfere with neutrophil functions.
The dose of elemental iron is = Whole blood hemoglobin deficit in g/dL x body weight (lb)
The duration can either be until the deficiency is resolved or as maintenance therapy.
Remember that all IV iron formulations carry some risks for anaphylactic reactions.
Iron Dextran (Dexferrum, Infed) – this agent is associated with most anaphylactic reactions and requires a test dose prior to full dose administration. Fatal reactions have been known to happen even with the test dose. Another unique adverse effect is the staining of the skin. It is the least expensive option.
Sodium Ferric Gluconate (Ferrlecit) – this agent has fewer anaphylactic events compared to the dextran formulation. The iron moiety is bound to one gluconate and four sucrose molecules. It is taken up by the phagocytic system and can cause hypotension.
Iron Sucrose (Venofer) – the iron moiety is bound in a sucrose complex. Like Ferrlecit, it is taken up by the phagocytic system and metabolized. Hypotension and leg cramps can occur.
There are newer generation IV iron formulations that have an iron core encapsulated in a shell to delay the iron release. The infusion rate depends on the stability of this shell. Some examples are ferric carboxymaltose and derisomaltose. The newest formulation is ferric derisomaltose (monoferric), which has a greater response than iron sucrose. Ferric carboxymaltose (Injectifer) is approved for use in CKD with no hemodialysis, but there was a problem with hypophosphatemia during the clinical trials.
Fermoxytol (Feraheme) was approved for patients with CKD or those who fail oral treatment. It can interfere with MRI and has a BBW for anaphylaxis if used with dextran or those with previous anaphylaxis.
Interesting note on iron supplementation in chronic heart failure: IV iron supplements (but not oral agents) have been shown to improve exercise capacity in heart failure patients (the FAIR-HF trial and IRONOUT-HF trial)
Monitoring and Follow-up
- Ferritin
- Transferrin saturation
- Hemoglobin
- Reticulocyte
- Tolerability of oral iron supplements