How to diagnose and manage a patient with microcytic hypochromic anemia?

Diagnosis and Management of Microcytic Hypochromic Anemia

Immediate Diagnostic Workup

Order serum ferritin first as the single most specific test for iron deficiency, using a cutoff of 45 μg/L for optimal sensitivity and specificity in clinical practice. 1, 2

• Ferritin <15 μg/L indicates absent iron stores, while <30 μg/L indicates low body iron stores 2
• In the presence of inflammation (elevated CRP), ferritin up to 100 μg/L may still represent iron deficiency 2
• Add transferrin saturation (TSAT) if ferritin appears falsely elevated due to inflammation; TSAT <16-20% confirms iron deficiency 2

Use RDW to distinguish iron deficiency from thalassemia trait: elevated RDW (>14.0%) with low MCV strongly indicates iron deficiency, while RDW ≤14.0% suggests thalassemia minor. 1, 2

• Low MCV (typically <80 fL), low MCH, and low MCHC confirm microcytic hypochromic anemia 1
• MCH is more reliable than MCV as it's less affected by storage conditions 2

Treatment Protocol

Start ferrous sulfate 200 mg (65 mg elemental iron) three times daily immediately, taken separately from meals, and continue for at least 3 months after hemoglobin normalizes to replenish iron stores. 1, 3, 2

• Add ascorbic acid (vitamin C) to enhance iron absorption 1, 3
• Alternative formulations include ferrous gluconate or ferrous fumarate if gastrointestinal side effects are intolerable 1, 3
• Expect hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks, which confirms iron deficiency diagnosis 1, 2
• Hemoglobin should increase by at least 2 g/dL within 4 weeks of adequate therapy 3, 2

Investigation for Underlying Blood Loss

Assume gastrointestinal blood loss until proven otherwise in any adult with iron deficiency anemia. 3

• Perform stool guaiac test for occult blood 3
• Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L warrant fast-track GI referral 2
• Obtain detailed menstrual history in premenopausal women, as heavy menstrual bleeding is the most common cause 3, 2
• Assess dietary intake for inadequate iron consumption 3

Monitoring Schedule

Recheck CBC at 2 weeks to confirm therapeutic response, then monitor hemoglobin and red cell indices every 3 months for 1 year, followed by annual monitoring. 1, 3, 2

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

Management of Treatment Failure

If no response after 4 weeks of adequate oral iron therapy, consider the following causes: 3, 2

• Non-compliance with medication 2
• Ongoing blood loss exceeding replacement capacity 3
• Malabsorption disorders: Screen for celiac disease, H. pylori infection, or autoimmune atrophic gastritis 2
• True intolerance to all oral formulations 3

Indications for Intravenous Iron

Switch to IV iron (iron sucrose or iron gluconate) if documented malabsorption, true intolerance to all oral formulations, or blood losses exceeding maximal oral replacement capacity. 3, 2

• Expect hemoglobin increase ≥2 g/dL within 4 weeks of IV iron administration 3, 2

Differential Diagnosis Considerations

Order hemoglobin electrophoresis if: 2

• Microcytosis persists with normal iron studies 2
• Appropriate ethnic background for hemoglobinopathy 2
• MCV disproportionately low relative to degree of anemia 2
• Family history of microcytic anemia 3

Consider anemia of chronic disease if: 2

• TSAT <20% with ferritin >100 μg/L 2
• Presence of inflammatory markers 2

Rare Genetic Disorders to Consider

IRIDA (Iron-Refractory Iron Deficiency Anemia): 2

• Remarkably low TSAT with low-to-normal ferritin 2
• Failure to respond to oral iron but may respond to IV iron 2
• Autosomal recessive TMPRSS6 mutations 2
• Requires repeated IV iron administration, though complete normalization rarely achieved 2

X-linked Sideroblastic Anemia (ALAS2 defects): 2

• Trial of pyridoxine (vitamin B6) 50-200 mg daily initially 2
• If responsive, continue lifelong supplementation at 10-100 mg daily 2

Other genetic disorders (SLC11A2, STEAP3, SLC25A38): 2

• Consider genetic testing if extreme microcytosis (MCV <70 fL) or family history present 2
• SLC25A38 defects: Hematopoietic stem cell transplantation is the only curative option 2

Critical Pitfalls to Avoid

Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish iron stores. 3

• Premature discontinuation leads to relapse 3

Do not assume all microcytic anemia is iron deficiency. 2

• Anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 2

Screen for combined deficiencies. 3

• Iron deficiency can coexist with B12 or folate deficiency 3

Do not rely on ferritin alone in inflammatory states. 2

• Ferritin can be falsely elevated by inflammation; add TSAT to diagnostic workup 2