Iron Deficiency Anemia

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): Menstrual blood loss, 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. Bleeding may be overt or occult.

2) Increased iron demand with inadequate supply: Adolescence, pregnancy, childhood and adolescence, extreme exercise, increased erythropoiesis during the treatment of cobalamin deficiency.

3) GI malabsorption of iron: After gastrectomy or various forms of bariatric surgery, Helicobacter pylori infection, autoimmune gastritis, 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 potent 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): Pica (craving and eating nonfood items: 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), cognitive impairment, restless leg syndrome, fatigue, emotional lability.

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

DiagnosisTop

Diagnostic Tests

1. Complete blood count (CBC): 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.

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, positive genetic screen, 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 (see Celiac Disease) 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 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. Anemia from iron deficiency should be corrected with iron repletion. Only in the setting of severe, symptomatic IDA or need for urgent correction should transfusion of RBCs be considered.

1. Patients with no known malabsorption: Consider the degree of iron deficiency, anemia, and etiology in addition to patient tolerance when selecting iron supplements. Dosing and optimal administration can vary based on the formulation. Iron salts are best absorbed on an empty stomach and with vitamin C and can be taken at 100 to 200 mg of elemental iron daily (lower doses [even 30 mg] may be effective as well). Note that iron should not be taken more often than once daily; dosing every other day can be considered to increase adherence if GI adverse effects are encountered. 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.

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 IV iron. 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 formulations are available. A total dose of 1 to 1.2 g is generally given and response monitored using the ferritin and hemoglobin levels.

There is a very low risk of severe adverse events from IV iron including hypersensitivity reactions. IV iron should be administered at a center appropriately trained and resourced to manage potential reactions.

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 route is a safe and effective option to consider in patients with iron deficiency refractory or intolerant to oral iron in the second and third trimester.

TablesTop