What is the diagnosis for a patient with hypoglobulinemia, decreased hematocrit, microcytic hypochromic anemia, elevated red cell distribution width, and evidence of iron deficiency?

Iron Deficiency Anemia

This presentation is classic for iron deficiency anemia (IDA), characterized by microcytic hypochromic anemia with depleted iron stores. The combination of low hemoglobin, hematocrit, MCV, and MCH alongside elevated RDW and low iron parameters (serum iron, ferritin, transferrin saturation) is pathognomonic for this condition 1.

Diagnostic Confirmation

The laboratory findings definitively establish iron deficiency anemia through multiple converging parameters:

• Serum ferritin is the single most powerful test for iron deficiency, with levels <30 μg/L diagnostic of low body iron stores in the absence of inflammation 2, 1.
• Transferrin saturation <16-20% confirms iron deficiency, distinguishing it from other causes of microcytic anemia 2, 1.
• The combination of low MCV with elevated RDW (>14.0%) strongly indicates iron deficiency anemia rather than thalassemia minor, which typically presents with low MCV but normal RDW 1.
• Low MCH combined with low MCHC confirms hypochromic anemia, most commonly from iron deficiency 1.

Distinguishing from Other Microcytic Anemias

This pattern excludes other common causes of microcytic anemia:

• Anemia of chronic disease would show ferritin >100 μg/L with transferrin saturation <20%, which is not present here 2.
• Thalassemia minor typically presents with normal or near-normal RDW and disproportionately low MCV relative to the degree of anemia, plus normal iron studies 1.
• Sideroblastic anemia would show elevated or normal ferritin with low transferrin saturation 1.

Critical Next Steps: Identifying the Source

Once iron deficiency anemia is confirmed, investigation of the underlying cause is mandatory in adults, as gastrointestinal blood loss (including occult malignancy) is the most common etiology in non-menstruating individuals 2, 1.

Investigation priorities include:

• Gastrointestinal evaluation is essential, particularly in men or post-menopausal women, as colorectal and gastric cancers commonly present with IDA 2.
• Menstrual history in pre-menopausal women, as heavy menstrual bleeding is the most common cause in this population 2.
• Dietary assessment for inadequate iron intake, particularly in vegetarians/vegans who have reduced heme iron absorption 2.
• Malabsorption screening, including celiac disease testing, especially if there is treatment failure with oral iron 1.
• NSAID use history, as these medications commonly cause occult GI blood loss 2.

Treatment Algorithm

First-line treatment is oral iron supplementation with ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores 1.

Expected response and monitoring:

• Hemoglobin should rise ≥10 g/L (or ≥2 g/dL) within 2-4 weeks if iron deficiency is the sole cause 1.
• Reticulocyte count should increase within 5-10 days of starting therapy 3.
• Continue iron supplementation for 3-6 months after hemoglobin normalization to fully replete iron stores 1, 3.

Alternative approaches if oral iron fails:

• Consider intravenous iron if malabsorption is present, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1.
• Alternative oral formulations (ferrous gluconate or ferrous fumarate) can be tried if ferrous sulfate is not tolerated 1.
• Adding ascorbic acid enhances iron absorption from oral preparations 1.

Common Pitfalls to Avoid

• Do not assume dietary insufficiency alone explains IDA in adults—gastrointestinal pathology must be excluded, particularly malignancy 2, 1.
• Do not rely on ferritin alone in inflammatory states, as it can be falsely elevated; add transferrin saturation to the workup 1.
• Do not overlook combined deficiencies—concurrent B12 or folate deficiency can mask the microcytosis of iron deficiency, presenting as normocytic anemia 1.
• Do not stop iron therapy when hemoglobin normalizes—stores must be repleted to prevent rapid recurrence 1, 3.

Rare Genetic Considerations

If the patient fails to respond to both oral and intravenous iron therapy, consider rare genetic disorders:

• Iron-refractory iron deficiency anemia (IRIDA) presents with remarkably low transferrin saturation, low-to-normal ferritin, and failure to respond to oral iron but may respond to IV iron 1.
• X-linked sideroblastic anemia (ALAS2 defects) may respond to pyridoxine (vitamin B6) 50-200 mg daily 1.
• Genetic testing should be considered if extreme microcytosis (MCV <70) or family history of refractory anemia is present 1.