*Iron Deficiency Anemia

Chapter: Iron Deficiency Anemia
McMaster Section Editor(s): Mark Crowther
Section Editor(s) in Interna Szczeklika: Andrzej Hellmann, Bogdan Ochrem
McMaster Author(s): Mark Crowther
Author(s) in Interna Szczeklika: Maria Podolak-Dawidziak
Additional Information

See also: 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).

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.

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.

Clinical FeaturesTop

1. Systemic manifestations of anemia.

2. Signs and symptoms of chronic iron deficiency (these may be absent in a substantial proportion of patients): Perverted appetite (clay, starch), 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).

DiagnosisTop

Diagnostic Tests

1. Complete blood count: Table 1; Table 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 1; Table 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. The colonoscopy may be skipped only in the case of gastric cancer or celiac disease diagnosis.

2) GI tract imaging if endoscopy is contraindicated.

3) Screening for celiac disease (anti–tissue transglutaminase [tTG] antibody or IgA endomysial antibody).

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 above.

Differential Diagnosis

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

TreatmentTop

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 (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). These preparations (except for iron hydroxide) should be taken on an empty stomach. If possible, avoid proton pump inhibitors. 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 intravenously or in exceptional cases intramuscularly while strictly observing the administration instructions recommended by the manufacturer. A single dose of parenteral iron is 100 to 200 mg of elemental iron and is usually given weekly or more often. Larger doses of selected agents are approved in some jurisdictions. 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.

TablesTop

Table 1. Differential diagnosis of hypochromic anemia

Parameter

Iron deficiency anemia

Anemia of chronic disease

Thalassemia alpha or beta

Sideroblastic anemia

Anemia severity

Any

Rarely Hb <9 g/dL

Mild

Any

MCV

N or ↓

↓↓

N, ↓, or ↑

Serum ferritin

N or ↑

N

TIBC

N

N

Iron

Serum

 

 

 

N

 

Bone marrow

↓ or absent

present

present

present

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

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

Parameter

Anemia

Anemia of chronic disease

Iron deficiency anemia

Severity

Hb usually ≥9 g/dL

Variable

Symptoms

Variable

Variable

Coincident illness

Always (anemia may be the presenting manifestation)

Variable

RBCs

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

↓↓

TIBC

Serum ferritin

N or ↑

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

Serum soluble transferrin receptor

N

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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