What is the recommended approach for assessing and treating iron deficiency anemia?

Assessment and Treatment of Iron Deficiency Anemia

The recommended approach for assessing iron deficiency anemia (IDA) includes confirming iron deficiency through serum ferritin testing, followed by appropriate gastrointestinal investigation to identify underlying causes, and initiating iron replacement therapy to restore hemoglobin levels and replenish iron stores.

Diagnosis of Iron Deficiency Anemia

Definition and Initial Assessment

• Anemia is defined as a hemoglobin (Hb) concentration below the lower limit of normal for the relevant population and laboratory 1
• Iron deficiency should be confirmed by iron studies prior to investigation, with serum ferritin being the single most useful marker 1
• A serum ferritin concentration <15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
• In the presence of inflammation, a ferritin cutoff of 45 μg/L provides a specificity of 0.92 for iron deficiency 1

Diagnostic Tests

• Hematological tests based on red cell characteristics (Hb, hematocrit, MCV, RDW) are more available and less expensive than biochemical tests 1
• Biochemical tests (erythrocyte protoporphyrin, serum ferritin, transferrin saturation) detect earlier changes in iron status 1
• A low MCV (microcytosis) and high RDW (>14.0%) suggest iron deficiency anemia 1
• A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even with equivocal iron studies 1

Investigation of Underlying Causes

When to Investigate

• GI investigation should be considered in all patients with confirmed IDA unless there is a history of significant non-GI blood loss 1
• Men and postmenopausal women with IDA should undergo urgent investigation due to higher risk of GI malignancy 1, 2
• In premenopausal women, investigation is warranted if IDA persists despite iron therapy or if there are concerning symptoms 3

Recommended Investigations

• Initial investigation should include urinalysis, screening for celiac disease, and endoscopic examination of the upper and lower GI tract 1
• Celiac disease is found in 3-5% of cases of IDA and should be routinely screened for serologically or by small bowel biopsy during gastroscopy 1
• In men and postmenopausal women, gastroscopy and colonoscopy should generally be first-line GI investigations 1, 3
• CT colonography is a reasonable alternative for those not suitable for colonoscopy 1
• If bidirectional endoscopy is negative with persistent or recurrent IDA, further investigation of the small bowel is recommended 1, 4
• Capsule endoscopy is the preferred test for examining the small bowel in IDA 1

Treatment Approach

Oral Iron Therapy

• Oral iron therapy should be initiated as first-line treatment with 100-200 mg daily dose of elemental iron 4
• Lower doses may be used if side effects occur 4
• Treatment duration of 3-6 months is often required to achieve therapeutic goals (normalization of hemoglobin and replenishment of iron stores) 4
• A simplified dose schedule (e.g., once daily) may improve compliance 1

Parenteral Iron Therapy

• Intravenous iron therapy should be considered when oral treatment lacks efficacy, causes intolerable side effects, or in cases of intestinal malabsorption or prolonged inflammation 5, 4
• FDA-approved IV iron formulations include iron sucrose and ferric gluconate, though these are specifically indicated for IDA in chronic kidney disease 6, 7

Follow-up

• Hemoglobin levels typically normalize with iron replacement therapy in most cases of IDA 1
• IDA may recur in a minority of patients on long-term follow-up, requiring reassessment 1
• If there is inadequate response to iron therapy or recurrent IDA despite negative initial investigations, further evaluation of the small bowel and renal tract is recommended 1

Special Considerations

• Anemia screening alone has limited usefulness as an indicator of iron deficiency, particularly in high-income countries where the prevalence has declined 8
• Race affects hemoglobin distribution, with certain populations having lower values than others even after adjustment for income 8
• Multiple factors besides iron deficiency can cause anemia, including other nutritional deficiencies, hereditary conditions, infection, and chronic inflammation 8
• In patients with chronic disease, inflammation may result in falsely normal ferritin levels despite iron deficiency 1