What is the appropriate diagnosis and treatment approach for a patient presenting with hypochromia?

Hypochromia: Diagnostic and Treatment Approach

Begin with serum ferritin as the single most specific test for iron deficiency, using a cut-off of 45 μg/L for optimal sensitivity and specificity, and simultaneously measure transferrin saturation (TSAT) and red cell distribution width (RDW) to differentiate iron deficiency from other causes of hypochromia. 1, 2

Initial Diagnostic Workup

The diagnostic algorithm must exclude common causes of microcytic hypochromic anemia systematically:

• Measure serum ferritin first - levels <30 μg/L indicate low body iron stores, though 45 μg/L provides optimal diagnostic accuracy 1, 2
• Check transferrin saturation (TSAT) - more sensitive than hemoglobin alone for detecting iron deficiency; TSAT <16-20% suggests iron deficiency 2, 3
• Evaluate RDW to differentiate causes:
  • RDW >14.0% with low MCV suggests iron deficiency anemia 1, 2
  • RDW ≤14.0% with low MCV suggests thalassemia minor 1, 2
• Order hemoglobin electrophoresis if microcytosis persists with normal iron studies, appropriate ethnic background, or MCV disproportionately low relative to anemia degree 2

Critical Diagnostic Pitfall

Do not assume normal hemoglobin excludes iron deficiency - hypochromic changes precede anemia development, and patients can have functional iron deficiency with normal hemoglobin levels 1. Additionally, 7% of patients have both thalassemia trait and iron deficiency, requiring ferritin measurement even when thalassemia is diagnosed 1.

Treatment Algorithm Based on Etiology

For Confirmed Iron Deficiency (Ferritin <45 μg/L)

Start ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least three months after anemia correction to replenish iron stores 1, 2:

• Add ascorbic acid to enhance iron absorption 1, 2
• Expected response: hemoglobin rise ≥10 g/L within 2 weeks confirms diagnosis 1, 2
• Continue treatment for 3 months after hemoglobin normalization to replenish stores 1, 2

For Non-Responders to Oral Iron

Consider intravenous iron if malabsorption is present, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1, 2:

• Evaluate for celiac disease, H. pylori infection, or autoimmune atrophic gastritis 4, 2
• Consider iron-refractory iron deficiency anemia (IRIDA) if remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron 4, 2
• For IRIDA, intravenous iron (iron sucrose or iron gluconate) is required as oral iron is typically ineffective 2

For Genetic Disorders of Iron Metabolism or Heme Synthesis

When hypochromia persists despite adequate iron stores, consider rare genetic disorders 4:

• X-linked sideroblastic anemia (ALAS2 defects): Start pyridoxine 50-200 mg daily initially; if responsive, continue lifelong supplementation at 10-100 mg daily 4, 2
• SLC11A2, STEAP3 defects: May require erythropoietin and/or erythrocyte transfusions based on individual needs 2
• SLC25A38 defects: Hematopoietic stem cell transplantation is the only curative option; symptomatic treatment includes transfusions and chelation therapy 4, 2
• Congenital erythropoietic porphyria (CEP) with severe microcytic hypochromic hemolytic anemia: Allogeneic HSCT should be considered as the only curative treatment; chronic transfusion with iron chelation as symptomatic treatment 4

Monitoring Protocol

Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year 1, 2:

• Provide additional oral iron if hemoglobin or MCV falls below normal 1, 2
• For patients receiving multiple transfusions or long-term iron therapy, monitor for iron overload with MRI of the liver in specific cases 2
• In patients with iron loading due to genetic defects (e.g., GLRX5), monitor iron status and treat iron overload with chelation therapy 4

Investigation of Underlying Cause

In adults with confirmed iron deficiency, investigate the source of iron loss 2:

• Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant fast-track gastrointestinal referral 2
• Occult gastrointestinal malignancy must be excluded 1
• Consider heavy menstrual bleeding in premenopausal women 2
• Evaluate for malabsorption disorders if dietary history suggests inadequate intake 2

Additional Diagnostic Considerations

Do not overlook combined deficiencies - iron deficiency can coexist with B12 or folate deficiency, requiring evaluation of macrocytic indices and vitamin levels 1, 2. In the presence of inflammation, ferritin up to 100 μg/L may still be consistent with iron deficiency, and TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease 2.