What is the diagnosis and treatment for a patient presenting with hypochromic microcytic anemia, characterized by low hemoglobin (hgb), low mean corpuscular volume (MCV), and low hematocrit?

Hypochromic Microcytic Anemia: Diagnosis and Management

Most Likely Diagnosis

This presentation of low hemoglobin, low MCV, and low hematocrit represents hypochromic microcytic anemia, with iron deficiency anemia being the most common cause. 1, 2

Diagnostic Confirmation

Serum ferritin is the single most useful marker for confirming iron deficiency anemia. 1, 3

• Ferritin <15 μg/L indicates absent iron stores 1
• Ferritin <30 μg/L indicates low body iron stores in the absence of inflammation 1, 4
• A cut-off of 45 μg/L provides optimal sensitivity and specificity in clinical practice 1, 3
• In the presence of inflammation, ferritin up to 100 μg/L may still be consistent with iron deficiency 1, 4

Additional Diagnostic Tests

• Transferrin saturation <20% is a more sensitive indicator of iron deficiency than hemoglobin alone 3, 4
• Mean corpuscular hemoglobin (MCH) is more reliable than MCV as it is less dependent on storage conditions and is reduced in both absolute and functional iron deficiency 1, 3
• Red cell distribution width (RDW) >14.0% with low MCV strongly suggests iron deficiency anemia, while RDW ≤14.0% suggests thalassemia minor 3, 4

Critical Pitfall to Avoid

Ferritin is an acute phase protein and can be falsely elevated in inflammatory states, making diagnosis challenging. 1, 4 If inflammation is suspected (elevated CRP, ESR, or clinical signs), add transferrin saturation to the workup. 1

First-Line Treatment

Oral iron supplementation with ferrous sulfate 200 mg three times daily for at least three months after anemia correction to replenish iron stores. 3, 4

• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 3
• Adding ascorbic acid enhances iron absorption 3, 4
• Recent evidence suggests intermittent dosing may be as effective as daily dosing with fewer side effects 5

Expected Response

A good response to iron therapy is defined as a hemoglobin rise ≥10 g/L within a 2-week timeframe, which confirms iron deficiency even if iron studies are equivocal. 1, 3, 4

When to Consider Intravenous Iron

If the patient fails to respond to oral iron therapy within 2-4 weeks, consider intravenous iron if malabsorption is present, with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 3, 4

Reasons for treatment failure include:

• Non-compliance 3
• Ongoing blood loss 3
• Malabsorption (celiac disease, H. pylori infection, autoimmune atrophic gastritis) 3
• True intolerance to oral preparations 2

Mandatory Investigation of Underlying Cause

Investigation should be considered at any level of anemia with confirmed iron deficiency, especially with more severe degrees, as patients are more likely to have serious underlying GI pathology. 1, 3

Fast-Track Referral Criteria

Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L warrant fast-track GI referral. 1, 3

Specific Investigations

• In adult men and post-menopausal women, gastrointestinal evaluation with upper endoscopy and colonoscopy is mandatory to exclude GI malignancy 4
• Consider small bowel biopsy during endoscopy to rule out celiac disease 4
• In premenopausal women, heavy menstrual bleeding is the most common cause 3

Differential Diagnosis Considerations

Do not assume all microcytic anemia is iron deficiency—hemoglobin electrophoresis should be ordered if microcytosis with normal iron studies, appropriate ethnic background, or MCV disproportionately low relative to degree of anemia. 1, 3

Other causes to consider:

• Anemia of chronic disease (transferrin saturation <20% with ferritin >100 μg/L) 1
• Thalassemia (MCV typically reduced out of proportion to the level of anemia, RDW ≤14.0%) 1, 3
• Sideroblastic anemia (rare, may respond to pyridoxine 50-200 mg daily) 3
• Genetic disorders of iron metabolism (IRIDA) if remarkably low transferrin saturation with low-to-normal ferritin and failure to respond to oral iron 3

Monitoring Protocol

Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year and then after a further year. 3, 4

• Repeat complete blood count after 4-8 weeks of treatment to assess response 4
• Provide additional oral iron if hemoglobin or MCV falls below normal 3
• For patients receiving multiple transfusions or long-term iron therapy, monitor for iron overload 3

Common Pitfalls

• Overlooking combined deficiencies, such as iron deficiency coexisting with B12 or folate deficiency 3, 4
• Failing to distinguish between iron deficiency anemia and anemia of chronic disease, which often overlap and require different management approaches 1, 4
• Missing thalassemia by not ordering hemoglobin electrophoresis in appropriate ethnic backgrounds 1, 3