Iron Deficiency Anemia

How to Cite This Chapter: Crowther M, Podolak-Dawidziak M. Iron Deficiency Anemia. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed July 29, 2021.
Last Updated: May 12, 2019
Last Reviewed: May 12, 2019
Chapter Information

Also see Anemia: General Considerations.

Definition, Etiology, PathogenesisTop

Iron deficiency anemia (IDA) is caused by an impaired heme synthesis due to systemic iron deficiency. It is characterized by the presence of microcytic red blood cells (RBCs) with a decreased hemoglobin (Hb) concentration (microcytic and hypochromic anemia) and abnormal parameters of iron metabolism (low ferritin levels, unless the patient has another reason for having an elevated ferritin level, such as systemic inflammation or liver disease).

Causes of iron deficiency:

1) Blood loss (the most frequent cause): Bleeding from the gastrointestinal (GI) (including bleeding caused by aspirin and other nonsteroidal anti-inflammatory drugs), urogenital (hematuria), or respiratory tract (chronic hemoptysis), trauma (including surgical procedures), multiple blood donations. Blood loss leading to iron deficiency is almost always clinically inapparent.

2) Increased iron demand with inadequate supply: Adolescence, pregnancy, breastfeeding, increased erythropoiesis in the course of treatment of cobalamin deficiency.

3) GI malabsorption of iron: After gastrectomy or various forms of bariatric surgery, Helicobacter pylori infection, autoimmune gastritis (~20 years before B12 deficiency manifestation), celiac disease, after intestinal resection, in low-protein diets, or due to high dietary contents of substances that decrease iron absorption (phosphates, oxalates, phytates, tannin).

4) Low dietary iron contents: Vegetarians.

5) Iron-refractory iron deficiency anemia (IRIDA): A rare autosomal-recessive disorder.

6) Chronic gastric acid suppression: A growing body of evidence suggests that long-term use of gastric acid suppressive therapy is associated with subsequent iron deficiency.

Clinical FeaturesTop

1. Systemic manifestations of anemia (see Anemia: General Considerations).

2. Signs and symptoms of chronic iron deficiency (these may be absent in a substantial proportion of patients): Perverted appetite (pica; clay, starch, ice, dirt), pain/tingling and smoothing of the tongue, dry skin, painful cheilosis, abnormalities of nails (pale, fragile nails with longitudinal stripes and furrows) and hair (fine, fragile hair with split ends).

3. Manifestations of the underlying condition (eg, colorectal cancer).


Diagnostic Tests

1. Complete blood count (CBC): Table 8.5-1; Table 8.5-2; decreased Hb levels (the decrease is more pronounced than the fall in red blood cell [RBC] counts), variable microcytosis, reticulocyte counts decreasing with the increasing severity of anemia. Differential blood count can reveal RBCs of varied sizes (anisocytosis) and shapes (poikilocytosis) in the case of partial treatment; leukopenia may be present (in ~10% of patients, usually those with severe iron deficiency). Reactive thrombocytosis is commonly seen and normalizes with treatment.

2. Parameters of iron metabolism: Table 8.5-1; Table 8.5-2. A decreased ferritin level is the best indicator of iron deficiency unless there is coincident inflammation.

3. Other tests used to diagnose the cause of IDA:

1) Upper and lower GI tract endoscopy: In every man and postmenopausal woman; in premenopausal woman in case of GI tract symptoms or signs, positive family colorectal cancer history, or iron refractoriness; additionally, where indicated by accepted age-specific and sex-specific colon cancer screening strategies.

2) GI tract imaging if endoscopy is contraindicated.

3) Screening for celiac disease (anti–tissue transglutaminase [tTG] antibody or IgA endomysial antibody) with endoscopic confirmation where appropriate.

4) Urine analysis to detect hematuria.

In case of unexplained and refractory IDA, consider H pylori testing; measurements of serum gastrin, antiparietal, or intrinsic factor antibodies; and capsule endoscopy.

Diagnostic Criteria

See Definition, Etiology, Pathogenesis, above.

Differential Diagnosis

Other types of anemia, particularly microcytic, and anemia of chronic disease (Table 8.5-1; Table 8.5-2).


This includes treatment of the underlying cause of iron deficiency as well as iron replacement therapy aimed at restoring normal ferritin levels. All patients with unexplained iron deficiency should be assumed to have GI malignancy until this is excluded with endoscopy. In case of severe symptomatic anemia, transfuse packed red blood cells (PRBCs).

1. Patients with no known malabsorption: Administer oral iron preparations in doses equivalent to 150 to 200 mg of elemental iron per day or every other day (lower doses [even 30 mg] may be effective as well) in the form of tablets, chewing gum, or syrup; alternatively, use fixed combinations of iron and ascorbic acid 100 to 200 mg/d (ascorbic acid increases GI iron absorption). Preparations vary in their requirement for being taken on an empty stomach. If possible, avoid  long-term gastric acid suppression therapy. The effectiveness of the therapy is evidenced by an increase in reticulocyte counts after 5 to 10 days of starting treatment and a slow increase in Hb concentration after 1 to 2 weeks of therapy. The treatment should be continued for 3 months after the normalization of Hb and ferritin levels.

2. Patients with intolerance of or refractoriness to oral iron supplements, persistent significant iron loss (eg, due to GI bleeding), treated with an erythropoiesis-stimulating agent in the setting of chemotherapy, with malabsorption, inflammatory bowel disease, chronic inflammatory disease, or chronic kidney disease: Use parenteral iron, usually IV or in exceptional cases IM while strictly observing the administration instructions recommended by the manufacturer. A variety of dosing regimens are currently available; for convenience,  administration of larger doses at lower frequency over smaller doses is generally desirable, where appropriate medications are available. A total dose of 1 to 1.2 g is generally given and response monitored using the ferritin and hemoglobin levels.

Due to the risk of severe hypersensitivity reaction (HSR), iron infusions should be given only at appropriately staffed sites equipped with resuscitation facilities. In case of HSR, stop the infusion. You may resume the iron infusion at 50% of the initial infusion rate after ≥15 minutes in case of mild HSR with spontaneous resolution.

Special ConsiderationsTop

Pregnant and breastfeeding women should receive prophylactic iron supplements in the dose of 30 mg/d, and in case of iron deficiency, 100 to 200 mg/d. Parenteral iron should be used with caution due to the risk of HSR.


Table 8.5-1. Differential diagnosis of hypochromic anemia


Iron deficiency anemia

Anemia of chronic disease

Thalassemia alpha or beta

Sideroblastic anemia

Anemia severity


Rarely Hb <9 g/dL

Mild (in trait)



↓ or ↓↓

N or ↓


N, ↓, or ↑

Serum ferritin

↓ (may be normal or increased with inflammation/liver disease)

N or ↑








Bone marrow

↓ or absent




↓, decreased; ↑, increased; Hb, hemoglobin; MCV, mean corpuscular volume; N, normal; TIBC, total iron binding capacity.

Table 8.5-2. Differential diagnosis of anemia of chronic disease and iron deficiency anemia



Anemia of chronic disease

Iron deficiency anemia


Hb usually ≥9 g/dL





Coincident illness

Always (anemia may be the presenting manifestation)



Usually normochromic and normocytic, but in patients with severe and long-lasting anemia it may be hypochromic and microcytic

Hypochromic and microcytic

Other cell lines

Usually normal but may reveal leukocytosis and high platelet counts (due to underlying condition)

Sometimes high platelet counts

Serum iron



Serum ferritin

N or ↑

↓ (may be N or ↑ in the setting of coincident inflammation)

Serum soluble transferrin receptor


Bone marrow iron

N or ↑

↓ or absent

↑, increased; ↓, decreased; Hb, hemoglobin; N, normal; RBC, red blood cell; TIBC, total iron binding capacity.

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