Management of Microcytosis with Low Hemoglobin, Hematocrit, MCV, and MCH
Order serum ferritin immediately as your first-line diagnostic test, as it is the most specific marker for iron deficiency anemia—the most common cause of microcytic anemia—and will guide your entire management algorithm. 1
Initial Diagnostic Workup
First-Line Laboratory Tests
- Serum ferritin <30 μg/L confirms iron deficiency anemia in the absence of inflammation, which is the most common cause of microcytosis 1, 2
- If inflammation is present (check CRP), ferritin up to 100 μg/L may still indicate iron deficiency 1
- Measure red cell distribution width (RDW): elevated RDW >14.0% with low MCV strongly suggests iron deficiency, while normal RDW ≤14.0% points toward thalassemia trait 1
Second-Line Tests (If Ferritin Not Clearly Low)
- Obtain complete iron panel: serum iron, total iron-binding capacity (TIBC), and transferrin saturation 1, 2
- Low iron with low TIBC and normal/high ferritin indicates anemia of chronic disease rather than iron deficiency 1
- Consider hemoglobin electrophoresis if thalassemia is suspected (elevated HbA2 suggests beta-thalassemia trait) 2, 3
Differential Diagnosis by Pattern
Iron Deficiency Anemia (Most Common: 35.2% of cases)
Thalassemia Trait (Second Most Common: Combined 50% of cases)
- Normal or elevated ferritin, normal RDW 1, 3
- Alpha-thalassemia (31.1%): requires genetic testing with gene mapping 3
- Beta-thalassemia (18.9%): elevated HbA2 on electrophoresis 2, 3
Anemia of Chronic Disease
- Low iron, low TIBC, normal/high ferritin 1
- MCV rarely falls below 70 fL; if MCV <67 fL, strongly reconsider iron deficiency 4
Rare Genetic Disorders
- Consider SLC11A2 defects in childhood-onset microcytic anemia with increased transferrin saturation 5
- Consider ALAS2 defects (X-linked sideroblastic anemia) in patients with unexplained iron loading 5
Investigation of Underlying Cause
For Confirmed Iron Deficiency
- In men and post-menopausal women, gastrointestinal blood loss is the most common cause and gastrointestinal malignancy must be excluded 1, 2
- Evaluate for: menstrual blood loss (pre-menopausal women), malabsorption, poor dietary intake, previous gastrectomy, NSAID use 1
- Proceed with upper and lower endoscopy to identify bleeding source 2
Treatment Algorithm
Iron Deficiency Anemia
- Start oral ferrous sulfate 200 mg three times daily for at least three months after hemoglobin correction 1
- Add ascorbic acid (vitamin C) to enhance absorption 1
- Switch to intravenous iron if: malabsorption is present, patient fails oral therapy, or losses exceed oral replacement capacity 1, 6
Monitoring Response
- Check hemoglobin and red cell indices at three-month intervals for one year, then annually 1
- Reticulocyte count should increase within 7-10 days of starting therapy 6
- Continue iron supplementation to replete stores, not just correct anemia 6
Thalassemia Trait
- No iron supplementation needed (may cause iron overload) 4
- Genetic counseling and family screening recommended 5
- Monitor for iron overload if transfusion-dependent 7
Critical Pitfalls to Avoid
- Never start iron therapy based solely on MCV without confirming iron deficiency with ferritin or iron studies, especially if TIBC is low, as this may cause iron overload in anemia of chronic disease 4
- Do not assume all microcytosis is iron deficiency—thalassemia represents 50% of cases in some populations 3
- In patients not responding to adequate oral iron after 2-3 months, consider malabsorption, ongoing blood loss, or alternative diagnosis 1
When to Refer to Hematology
- Refractory microcytic anemia despite adequate iron supplementation for 3 months 1
- Suspected genetic disorders (consider genetic testing for SLC11A2, ALAS2, or thalassemia genes) 5, 1
- Unexplained microcytic anemia with increased transferrin saturation 5
- MCV remains unexplained after complete workup (6.9% of cases may represent non-deletional alpha-thalassemia) 3