What is the initial management approach for a premenopausal woman with microcytic hypochromic anemia and low red blood cell (RBC) count, potentially due to iron deficiency or other underlying conditions?

Management of Microcytic Hypochromic Anemia in Premenopausal Women

Start oral ferrous sulfate 324 mg (65 mg elemental iron) one to three times daily for at least three months after hemoglobin normalizes, as this is first-line treatment for iron deficiency anemia, the most common cause of microcytic hypochromic anemia in premenopausal women. 1, 2

Initial Diagnostic Workup

Serum ferritin is the single most useful test to confirm iron deficiency:

• Ferritin <15 μg/L indicates absent iron stores 1, 2, 3
• Ferritin <30 μg/L indicates low body iron stores 1, 2
• Use a cut-off of 45 μg/L for optimal sensitivity and specificity in practice 1, 2
• Ferritin >100 μg/L makes iron deficiency almost certainly not present 3

Add transferrin saturation (TSAT) if ferritin appears falsely elevated (inflammation, infection, malignancy, or liver disease can elevate ferritin as an acute phase reactant):

• TSAT <16-20% confirms iron deficiency 1
• TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease instead 1

Use RDW to distinguish iron deficiency from thalassemia trait:

• Low MCV with RDW >14.0% suggests iron deficiency anemia 1, 2
• Low MCV with RDW ≤14.0% suggests thalassemia minor 1, 2
• Elevated red cell count with microcytosis also points to thalassemia trait 3

Treatment Protocol

Oral iron supplementation:

• Ferrous sulfate 324 mg (65 mg elemental iron) one to three times daily 1, 2
• Continue for at least three months after hemoglobin normalizes to replenish iron stores 1, 2
• Add ascorbic acid (vitamin C) to enhance absorption 1, 2
• Switch to ferrous gluconate or ferrous fumarate if gastrointestinal side effects are intolerable 1, 2

Expected response confirming iron deficiency:

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks 1, 2
• Expect at least 2 g/dL increase within 4 weeks 1, 2

Monitoring Schedule

Check hemoglobin, MCV, and iron studies:

• At 2 weeks to confirm response 2
• At 4 weeks 2
• At 3 months 1, 2
• Every 3 months for the first year 1, 2
• Then annually thereafter 1, 2

Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 1, 2

Investigation of Underlying Cause

In premenopausal women, heavy menstrual bleeding is the most common cause 1, but all adults with confirmed iron deficiency require investigation of the source of iron loss 1:

Fast-track gastrointestinal referral is warranted for:

• Non-menstruating women with Hb <100 g/L 1
• Any patient with gastrointestinal symptoms 1

Consider additional causes:

• Gastrointestinal blood loss (melena, hematochezia, occult bleeding) 1
• Malabsorption disorders (celiac disease, H. pylori infection, autoimmune atrophic gastritis) 1
• Dietary inadequacy 1

Screen for celiac disease if malabsorption is suspected 1

Management of Treatment Failure

If no response within 2-4 weeks, consider:

• Non-compliance with oral iron 1
• Ongoing blood loss 1
• Malabsorption 1
• True intolerance to oral preparations 1

Switch to intravenous iron if malabsorption is confirmed:

• Use iron sucrose or iron gluconate 1, 2
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks 1

Order hemoglobin electrophoresis if:

• Microcytosis persists with normal iron studies 1
• MCV is disproportionately low relative to degree of anemia 1
• Appropriate ethnic background for thalassemia 1

Consider rare genetic disorders if:

• Extreme microcytosis (MCV <70) 1
• Family history of refractory anemia 1
• Very low TSAT with low-to-normal ferritin (suggests IRIDA) 1, 2
• Failure to respond to both oral and intravenous iron 1

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 1

Do not overlook combined deficiencies - iron deficiency can coexist with B12 or folate deficiency 1

Do not presume haemoglobinopathies based on ethnicity alone - laboratory confirmation is required 3

In the presence of inflammation, ferritin up to 100 μg/L may still be consistent with iron deficiency 1, so add TSAT to the workup 1

Monitor for iron overload in patients receiving multiple transfusions or long-term iron therapy - consider MRI of the liver in specific cases 1