Management of Microcytic Anemia with Normal MCHC
The first-line approach is to measure serum ferritin to diagnose iron deficiency anemia, followed by oral ferrous sulfate 200 mg three times daily for at least three months after hemoglobin correction if ferritin is low. 1
Initial Diagnostic Workup
The diagnostic algorithm should proceed systematically based on specific laboratory parameters:
- Measure serum ferritin first as it is the most specific test for iron deficiency, with levels <15 μg/L indicating absent iron stores and <30 μg/L indicating low stores 1, 2
- Use a ferritin cut-off of 45 μg/L for optimal sensitivity and specificity in clinical practice 1, 2
- Evaluate transferrin saturation (TSAT) as it is more sensitive than hemoglobin alone for detecting iron deficiency 1, 2
- Check the RDW (red cell distribution width) to differentiate causes: RDW >14.0% suggests iron deficiency anemia, while RDW ≤14.0% suggests thalassemia minor 1, 2
Treatment Algorithm for Iron Deficiency Anemia
Once iron deficiency is confirmed, initiate treatment immediately:
- Start ferrous sulfate 200 mg orally three times daily and continue for at least three months after anemia correction to replenish iron stores 1, 2
- Add ascorbic acid (vitamin C) to enhance iron absorption 1, 2
- Switch to ferrous gluconate or ferrous fumarate if the patient cannot tolerate ferrous sulfate due to gastrointestinal side effects 1, 2
- Expect a hemoglobin rise ≥10 g/L within 2 weeks as confirmation of iron deficiency and adequate response 1, 2
Management of Non-Responders
If the patient fails to respond to oral iron therapy within 2-4 weeks:
- Consider intravenous iron if malabsorption is present, expecting a hemoglobin increase of at least 2 g/dL within 4 weeks 1, 2
- Test for thalassemia if RDW is normal or near-normal despite low MCV 1
- Evaluate for genetic disorders of iron metabolism (such as IRIDA, SLC11A2 defects) or heme synthesis disorders, particularly if ferritin is low-normal (>20 mg/L) with low TSAT or if there is family history of refractory anemia 1, 2
- Screen for celiac disease if malabsorption is suspected 1
Special Considerations for Genetic Disorders
When genetic causes are identified or suspected:
- For X-linked sideroblastic anemia (ALAS2 defects): Initiate pyridoxine (vitamin B6) 50-200 mg daily as initial dose, with expected response leading to lifelong supplementation at 10-100 mg daily 1
- For TMPRSS6 defects (IRIDA): Administer intravenous iron repeatedly (iron sucrose or ferric gluconate), though complete normalization is rarely achieved 1
- For severe genetic disorders: Consider erythropoietin, transfusions, or hematopoietic stem cell transplantation in severe cases 1
Monitoring Protocol
Establish a structured follow-up schedule:
- Monitor hemoglobin and red cell indices at 3-month intervals for one year, then again after a further year 1, 2
- Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 1, 2
- Monitor for iron overload in patients receiving multiple transfusions or long-term iron therapy 1, 2
- Consider liver MRI in specific cases to detect toxic iron loading early, particularly in genetic disorders where normal serum ferritin does not exclude liver iron loading 1, 2
Critical Pitfalls to Avoid
- Do not assume all microcytic anemia is iron deficiency: Anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated to avoid unnecessary iron therapy 1
- Do not overlook combined deficiencies: Iron deficiency can coexist with B12 or folate deficiency 1, 2
- Do not rely solely on MCV for classification: Normal MCHC with low MCV can occur in various conditions, and MCV-guided classification alone may incorrectly rule out certain etiologies 3
- Investigate the underlying cause: In men and post-menopausal women, evaluate for gastrointestinal blood loss or malabsorption as the source of iron deficiency 1, 2