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

Management of Microcytic Hypochromic Anemia with Anisopoikilocytosis

Start with oral ferrous sulfate 200 mg three times daily for at least three months after hemoglobin normalizes, while simultaneously investigating the underlying source of iron loss, particularly gastrointestinal bleeding in adults. 1

Diagnostic Confirmation

• Serum ferritin is the most specific initial test, with levels <15 μg/L indicating absent iron stores and <30 μg/L indicating low body iron stores. 1
• A ferritin cut-off of 45 μg/L provides optimal sensitivity and specificity for iron deficiency in clinical practice. 1, 2
• MCH (mean cell hemoglobin) is more reliable than MCV as it is less dependent on storage conditions and is reduced in both absolute and functional iron deficiency. 1
• Elevated RDW (>14.0%) combined with low MCV strongly distinguishes iron deficiency anemia from thalassemia minor, where RDW is typically normal or near-normal. 2, 3
• If ferritin appears falsely elevated due to inflammation (as an acute phase protein), add transferrin saturation to the workup, with TSAT <16-20% confirming iron deficiency. 1, 2

First-Line Treatment Protocol

• Oral ferrous sulfate 324 mg (65 mg elemental iron) one to three times daily is the standard first-line treatment. 3, 4
• Continue treatment for at least three months after hemoglobin normalizes to fully replenish iron stores. 2, 3
• Adding ascorbic acid (vitamin C) 200-500 mg with each iron dose enhances absorption. 2, 3
• Alternative formulations include ferrous gluconate or ferrous fumarate if gastrointestinal side effects occur with ferrous sulfate. 1, 2, 3

Expected Response and Monitoring

• Hemoglobin should rise ≥10 g/L (≥1 g/dL) within 2 weeks, confirming iron deficiency as the cause. 2, 3
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of starting treatment. 2, 3
• Monitor hemoglobin and red cell indices at 2 weeks, 4 weeks, 3 months, then every 3 months for the first year, then annually. 2, 3

Mandatory Investigation for Underlying Cause

• Investigation should be considered at any level of anemia with confirmed iron deficiency, though the case is stronger with more severe degrees of anemia. 1
• Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L warrant fast-track gastrointestinal referral to exclude malignancy. 1, 2, 3
• Evaluate for gastrointestinal blood loss (melena, hematochezia, occult bleeding), menstrual blood loss, dietary inadequacy, and malabsorption disorders (celiac disease, H. pylori, autoimmune atrophic gastritis). 2, 3

When to Consider Intravenous Iron

• Consider IV iron if malabsorption is documented, patient cannot tolerate oral iron, ongoing blood loss exceeds oral replacement capacity, or no hemoglobin response after 4 weeks of adequate oral therapy. 2, 3
• Expected hemoglobin increase with IV iron is at least 2 g/dL within 4 weeks. 2, 3
• Iron sucrose or iron gluconate are the preferred IV formulations. 2

Critical Differential Diagnosis Considerations

• Order hemoglobin electrophoresis if microcytosis persists with normal iron studies, particularly in patients with appropriate ethnic background or MCV disproportionately low relative to degree of anemia, to exclude thalassemia. 1, 2
• Consider genetic disorders of iron metabolism or heme synthesis if:
  • Extreme microcytosis (MCV <70 fL) is present 2
  • Family history of refractory anemia exists 1, 2
  • Remarkably low transferrin saturation with low-to-normal ferritin (>20 μg/L) suggests IRIDA 2
  • Failure to respond to both oral and IV iron 2

Rare Genetic Causes Requiring Specialized Management

• For IRIDA (TMPRSS6 defects): Repeated IV iron (iron sucrose or iron gluconate) increases hemoglobin and ferritin, though complete normalization is rarely achieved. 2
• For X-linked sideroblastic anemia (ALAS2 defects): Trial of pyridoxine (vitamin B6) 50-200 mg daily initially, with lifelong maintenance at 10-100 mg daily if responsive. 1, 2, 5
• For SLC25A38 defects: Hematopoietic stem cell transplantation is the only curative option, with symptomatic treatment including transfusions and chelation therapy. 2, 5
• Monitor for iron overload in patients receiving multiple transfusions or long-term iron therapy, and consider MRI of the liver in specific cases to detect toxic iron loading early. 1, 2

Common Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease (TSAT <20% with ferritin >100 μg/L), thalassemia, and sideroblastic anemia require different management. 2, 6
• Do not use ferritin alone in inflammatory states, as it can be falsely elevated; add transferrin saturation to accurately diagnose iron deficiency. 1, 2
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, which microcytosis and hypochromia lose sensitivity for in the presence of chronic disease or vitamin deficiencies. 1
• Do not fail to investigate the source of iron loss in adults with confirmed iron deficiency, as gastrointestinal malignancy must be excluded. 1, 3