What is the diagnosis and treatment for a patient with microcytic anemia, low iron, and low ferritin?

Iron Deficiency Anemia: Diagnosis and Treatment

Diagnosis

This patient has clear-cut iron deficiency anemia based on ferritin 8 μg/L, iron saturation 5%, microcytic hypochromic indices (MCV 78.7, MCH 24.5, MCHC 31), and elevated RDW 16. 1, 2

Diagnostic Confirmation

• Ferritin <15 μg/L is highly specific (specificity 0.99) for iron deficiency and indicates absent iron stores. 1, 2
• The combination of low MCV with elevated RDW >14% strongly distinguishes iron deficiency anemia from thalassemia trait, which typically shows RDW ≤14%. 2
• Transferrin saturation <16-20% (this patient has 5%) confirms iron deficiency. 1, 2
• MCH is actually more reliable than MCV as a marker of iron deficiency because it's less dependent on storage conditions and the counting machine used. 1

Treatment Protocol

Start oral ferrous sulfate 324 mg (65 mg elemental iron) three times daily for at least three months after hemoglobin correction to replenish iron stores. 2, 3

Expected Response and Monitoring

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks if iron deficiency is the cause. 2
• A hemoglobin increase of at least 2 g/dL within 4 weeks confirms appropriate response. 2
• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year. 2
• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up. 2

Alternative Formulations

• If ferrous sulfate is not tolerated due to gastrointestinal side effects, switch to ferrous gluconate or ferrous fumarate. 2
• Adding ascorbic acid (vitamin C) can enhance iron absorption. 2

Investigation of Underlying Cause

In adults with confirmed iron deficiency anemia, investigation for the source of iron loss is mandatory. 1, 2

Key Investigations Required

• Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant fast-track gastrointestinal referral. 1, 2
• However, investigation should be considered at any level of anemia with confirmed iron deficiency, as these cut-offs will miss some cases of colorectal cancer. 1
• Bidirectional endoscopy (upper endoscopy with small bowel biopsies and colonoscopy) is essential to rule out gastrointestinal blood loss, celiac disease (present in 2-3% of iron deficiency anemia patients), colonic cancer, polyps, and angiodysplasia. 2

Additional Considerations

• Evaluate for heavy menstrual bleeding in premenopausal women, which is the most common cause in this population. 2
• Screen for celiac disease if malabsorption is suspected, as it can cause iron deficiency anemia. 2
• Consider H. pylori infection or autoimmune atrophic gastritis as potential causes of malabsorption. 2, 4

Management of Treatment Failure

If the patient fails to respond to oral iron therapy within 2-4 weeks, consider the following:

• Non-compliance with medication. 2
• Ongoing blood loss that exceeds iron replacement. 2
• Malabsorption disorders (celiac disease, H. pylori, atrophic gastritis). 2
• True intolerance to oral iron preparations. 2

Intravenous Iron Indications

• Consider intravenous iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 2
• IV iron is preferred when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. 4

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency: anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated to avoid unnecessary iron therapy. 2
• Order hemoglobin electrophoresis if microcytosis persists with normal iron studies or if MCV is disproportionately low relative to the degree of anemia, particularly in patients with appropriate ethnic background for thalassemia. 1, 2
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW. 2
• In the presence of inflammation, ferritin up to 100 μg/L may still be consistent with iron deficiency, so add transferrin saturation to confirm the diagnosis. 1

Rare Genetic Considerations

If there is failure to respond to both oral and intravenous iron, consider rare genetic disorders:

• Iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 mutations presents with remarkably low transferrin saturation, low-to-normal ferritin, and resistance to oral iron but may respond to repeated IV iron. 2, 4
• X-linked sideroblastic anemia (ALAS2 defects) may respond to pyridoxine (vitamin B6) 50-200 mg daily initially, then 10-100 mg daily lifelong if responsive. 2
• Consider genetic testing if extreme microcytosis (MCV <70), family history of refractory anemia, or paradoxical iron overload is present. 2, 5