What is the appropriate management for a patient presenting with microcytic hypochromic anemia?

Management of Microcytic Hypochromic Anemia

Start oral ferrous sulfate 200 mg three times daily immediately while simultaneously investigating the underlying cause, as iron deficiency is the most common etiology and requires both treatment and identification of the source of iron loss. 1, 2

Diagnostic Confirmation

Serum ferritin is your single most important diagnostic test:

• Ferritin <15 μg/L indicates absent iron stores 1
• Ferritin <30 μg/L indicates low body iron stores 1
• A cutoff of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in practice 1
• Ferritin >150 μg/L makes absolute iron deficiency unlikely 1

Add transferrin saturation (TSAT) if inflammation is present, as ferritin can be falsely elevated as an acute phase reactant 1:

• TSAT <16-20% suggests iron deficiency 1
• TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease 1
• In inflammatory states, ferritin up to 100 μg/L may still represent iron deficiency 1

Use RDW to differentiate causes:

• Low MCV with RDW >14.0% suggests iron deficiency anemia 1
• Low MCV with RDW ≤14.0% suggests thalassemia minor 1

First-Line Treatment Protocol

Oral iron supplementation is the cornerstone of therapy:

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily, taken separately from meals 1, 2
• Continue for at least 3 months after hemoglobin normalizes to replenish iron stores 1, 2
• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 1, 2
• Adding ascorbic acid (vitamin C) enhances iron absorption 1, 2

Expected response to confirm diagnosis:

• Hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the cause 1, 2
• Recheck CBC at 2 weeks to confirm response 2

Mandatory Investigation of Underlying Cause

Assume gastrointestinal blood loss until proven otherwise 2:

• Men with Hb <110 g/L warrant fast-track GI referral 1
• Non-menstruating women with Hb <100 g/L warrant fast-track GI referral 1
• Perform stool guaiac test for occult blood 2
• Consider endoscopy if GI symptoms present 1

In premenopausal women, obtain detailed menstrual history, as heavy menstrual bleeding is the most common cause 1, 2

Screen for malabsorption disorders if treatment fails:

• Celiac disease 1
• H. pylori infection 1
• Autoimmune atrophic gastritis 1

Monitoring Schedule

Follow this algorithmic approach:

• Recheck CBC at 2 weeks to confirm response (Hb rise ≥10 g/L) 1, 2
• Monitor hemoglobin and red cell indices every 3 months for 1 year 1, 2
• Then monitor annually 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 1

When to Switch to Intravenous Iron

Consider IV iron (iron sucrose or iron gluconate) if:

• Documented malabsorption is present 1, 2
• True intolerance to all oral formulations 2
• Blood losses exceed maximal oral replacement capacity 2
• Expected hemoglobin increase of at least 2 g/dL within 4 weeks of IV iron 1, 2

Red Flags Requiring Further Investigation

Failure to respond to adequate oral iron therapy after 4 weeks suggests:

• Non-compliance 1
• Ongoing blood loss 1
• Malabsorption 1
• Genetic disorders of iron metabolism 1

Order hemoglobin electrophoresis if:

• Microcytosis with normal iron studies 1
• Appropriate ethnic background for thalassemia 1
• MCV disproportionately low relative to degree of anemia 1
• Persistent microcytosis despite iron repletion 2

Rare Genetic Causes to Consider

IRIDA (Iron-Refractory Iron Deficiency Anemia):

• Remarkably low TSAT with low-to-normal ferritin 1
• Failure to respond to oral iron but may respond to IV iron 1
• Autosomal recessive TMPRSS6 mutations 1
• Requires repeated IV iron (iron sucrose or iron gluconate), though complete normalization is rarely achieved 1

X-linked Sideroblastic Anemia (ALAS2 defects):

• Trial of pyridoxine (vitamin B6) 50-200 mg daily initially 1
• If responsive, continue lifelong at 10-100 mg daily 1

Other genetic disorders (SLC11A2, STEAP3, SLC25A38):

• Consider genetic testing if extreme microcytosis (MCV <70) or family history present 1
• May require erythropoietin, transfusions, or stem cell transplantation in severe cases 1

Critical Pitfalls to Avoid

Do not assume all microcytic anemia is iron deficiency - anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 1

Do not stop iron therapy when hemoglobin normalizes - continue for 3 months to replenish stores or relapse will occur 2

Do not overlook combined deficiencies - iron deficiency can coexist with B12 or folate deficiency 1, 2

Do not use ferritin alone in inflammatory states - add TSAT to accurately diagnose iron deficiency 1

Do not forget to investigate the source of iron loss - treatment without identifying the cause leads to recurrence 1, 2