Iron Deficiency Anemia (IDA): Epidemiology, Classification, Diagnosis, and Treatment

Iron deficiency anemia is a pathology that develops when iron loss exceeds iron intake in the body. It is often due to iron deficiency resulting from blood loss, insufficient dietary intake, or impaired absorption in the intestines, as well as increased demand, for example, during pregnancy. As a result, there is a reduction in hemoglobin concentration and a decrease in the number of red blood cells in the blood.

Epidemiology

Iron deficiency anemia is a global health issue. This disease is widespread, not linked to geographical location or socio-economic processes, and affects over one billion people (27% of the population).

According to the World Health Organization (WHO), the prevalence of anemia in 2011 was:

• 42% among children;
• 29% among non-pregnant women;
• 38% among pregnant women.

In 2013, iron deficiency was recognized as and continues to be the main cause of anemia.

Conditions associated with low iron levels are widespread among women in high-income countries. About 38% of non-pregnant women have an iron deficiency but without anemia, and 13% develop iron deficiency anemia.

Pregnancy significantly increases the risk: in the third trimester, iron deficiency is observed in most pregnant women (84%).

Groups at increased risk of developing iron deficiency anemia also include the following people:

• Taking non-steroidal anti-inflammatory drugs;
• Suffering from inflammatory bowel diseases (13%-90%);
• Suffering from chronic inflammatory conditions, including chronic kidney disease (24%-85%), heart failure (37%-61%), and cancer (18%-82%).

Pathophysiology

Iron enters the body through dietary intake. The most absorbable form is heme iron. It is found in animal-based foods (red meat, poultry, and seafood).

In addition, there is non-heme iron, which can be obtained from plant products such as legumes, vegetables (e.g., dried beans, leafy greens), and grains.

Both forms are absorbed in the duodenum. Then, with the help of a special transport protein, ferroportin, iron enters the bloodstream and binds to transferrin.

Transferrin transports iron to the liver, spleen, and bone marrow for red blood cell production and storage. Inside the cell, iron binds to ferritin to prevent cellular damage from free radical formation.

Iron absorption and storage are regulated by the hormone hepcidin, which is synthesized in the liver. It blocks ferroportin and promotes its degradation. This prevents the absorption and release of iron stored in the liver, spleen, and bone marrow.

When iron levels in the body are low, hepcidin levels drop, which helps iron be better absorbed and released from storage sites. On the contrary, excess iron or inflammation stimulates hepcidin production by the liver. As a result, iron absorption into the bloodstream and ferritin release are blocked, disrupting hemoglobin synthesis.

Prolonged high levels of hepcidin may eventually lead to iron deficiency and consequent anemia.

Classification of Iron Deficiency Anemia

All anemias are classified by severity as follows:

• Mild: 90–120g/L;
• Moderate: 70–90g/L;
• Severe: less than 70g/L.

By red blood cell size:

• Microcytic (MCV < 80fL): often in iron deficiency anemia, anemia of chronic disease, thalassemias;
• Normocytic (MCV 80–100fL): in anemia of chronic disease, chronic kidney disease, and sickle cell anemia, and is possible in early-detected iron deficiency anemia;
• Macrocytic (MCV > 100fL): with B12 deficiency, folate deficiency anemia, liver diseases.

Clinical presentation

Iron deficiency anemia may progress slowly. In such a case, there will be no symptoms. Also, symptoms may not be present in mild anemia, or they may be non-specific.

Symptoms:

• Fatigue;
• Increased fatigue;
• Paleness of the skin;
• Dizziness;
• Increased fatigue;
• Sleep disorders;
• Shortness of breath (can occur at rest or with minimal physical exertion);
• Tachycardia.

During a clinical examination, the following signs may be detected:

• Conjunctival pallor,
• Glossitis (atrophy of the tongue’s mucosa),
• Cheilosis (cracks at the corners of the mouth),
• Koilonychia (“spoon nails”).

Diagnosis

Laboratory Tests

• Complete blood count: hemoglobin below 130g/L in men, below 120g/L in women, below 110g/L in pregnant women. Normocytic or microcytic, hypochromic red blood cells, low reticulocyte count.
• Blood biochemistry: decreased levels of serum iron and ferritin, increased transferrin.

Instrumental diagnostic methods

Mandatory diagnostic tests are used to rule out other pathologies that may cause anemia:

• Chest X-ray: exclusion of lung and mediastinal tumors, tuberculosis;
• Esophagogastroduodenoscopy: exclusion of stomach or duodenal ulcers caused by Helicobacter pylori, bleeding, or esophageal or stomach tumors;
• Colonoscopy: exclusion of polyps, intestinal neoplasms, bleeding;
• Ultrasound of the abdominal cavity and retroperitoneal space: exclusion of tumor, splenic enlargement, hepatitis;
• Gynecological examination: exclusion of gynecological pathology that may cause anemia (heavy menstruation or uterine fibroids).

Additional diagnostic methods include testing stool for occult blood, helminths, and protozoa, as well as bone marrow aspirate examination (myelogram).

Differential diagnosis

For accurate diagnosis, it is important to differentiate iron deficiency anemia from other forms of anemia, especially anemia with chronic diseases.

Comparison of iron deficiency anemia and anemia of chronic disease

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Treatment and iron level correction strategy

Treatment aims to eliminate the primary cause of blood loss, inflammation, or impaired absorption and to replenish iron deficiency.

Red blood cell transfusion is indicated in severe iron deficiency anemia.

Oral iron intake

Oral iron intake is an economically accessible and highly effective treatment method for iron deficiency anemia in stable outpatients. Iron salts (iron gluconate, iron sulfate, and iron fumarate) are the first-line choice agents for treating this condition.

Among oral forms, iron sulfate is recognized as the “gold standard.” This is due to its high bioavailability, economic efficiency, and widespread use worldwide. It, like other iron salts, quickly increases blood iron levels, effectively boosting hemoglobin and iron stores.

The intake of medications depends on the severity of iron deficiency anemia. Medications must be taken for at least 4–6 months until normalization of hemoglobin levels and 2–3 months thereafter until ferritin levels are normal, but more time may be necessary.

For better absorption, iron preparations should be taken:

• On an empty stomach or between meals;
• Together with vitamin C (orange juice or ascorbic acid);
• Avoid concurrent intake with calcium-containing products, such as dairy products, as well as with tea and coffee.

As well, the concurrent intake of iron with medications that decrease stomach acidity (antacids) can potentially interfere with iron absorption.

It should be noted that the use of oral iron preparations is considered safe but can often lead to:

• Nausea;
• Vomiting;
• Constipation;
• Diarrhea;
• Abdominal pain;
• Black tarry stools.

Iron salts can also cause tooth discoloration and a metallic taste in the mouth. These effects are particularly noticeable when liquid forms of medication are used over the long term or are improperly diluted before consumption.

Iron absorption

The absorption of iron depends on its valency: ferrous iron is absorbed directly, whereas ferric iron requires preliminary reduction.

Some modern iron preparations, such as polysaccharide, citrate, and sucrosomal iron, according to manufacturers’ recommendations, can be taken irrespective of meals.

Although ferric iron is often considered gentler on the stomach than ferrous iron, there are few direct comparative studies.

Sucrosomal iron in capsules is well tolerated by the gastrointestinal tract and has demonstrated efficacy in patients with iron deficiency anemia who did not tolerate or were resistant to iron sulfate and in women with postpartum anemia.

Similar data on good tolerance have been obtained in patients with inflammatory bowel diseases and chronic kidney disease (not on dialysis) taking liposomal iron.

Iron maltol and sucrosomal iron are promising new oral forms of iron supplements. However, their efficacy compared to traditional iron salts is unproven, and they are significantly more expensive. Despite demonstrating comparable therapeutic results with intravenous iron administration in some cases, they require several months of intake for complete replenishment of stores.

Additional randomized controlled trials with sufficient statistical power are needed to fully understand the efficacy, side effects, optimal dosages, and frequency of intake of various oral iron preparations in different patient groups.

Intravenous iron administration

Intravenous iron administration is the preferred method of therapy in cases where there is resistance to oral forms or unsatisfactory tolerance.

Moreover, this approach is justified in patients requiring rapid replenishment of iron stores since it bypasses the absorption phase in the gastrointestinal tract, ensuring direct bioavailability.

This method is superior to oral administration in effectiveness due to the following reasons:

• It normalizes hemoglobin levels faster;
• It reduces the need for the packed RBCs transfusions;
• It improves the quality of life for patients with chronic heart failure, inflammatory bowel diseases, chronic kidney diseases undergoing hemodialysis, and anemia associated with malignancies.