Next Steps for Microcytic Anemia with Elevated RDW
Order serum ferritin and transferrin saturation immediately—this pattern of low MCV, MCH, MCHC with elevated RDW is highly specific for iron deficiency anemia, which requires both confirmation and investigation of the underlying blood loss source. 1, 2
Immediate Laboratory Workup
Essential first-line tests:
- Serum ferritin (most powerful single test): <30 μg/L confirms iron deficiency in the absence of inflammation; <100 μg/L indicates deficiency when inflammation is present 3, 1
- Transferrin saturation: <15-16% supports iron deficiency and is less affected by inflammation than ferritin 4, 1
- C-reactive protein: needed to interpret ferritin correctly, as inflammation falsely elevates ferritin levels 4, 1
- Reticulocyte count: evaluates bone marrow response to anemia 4, 2
Diagnostic Interpretation
The combination you describe has 91.4% accuracy for iron deficiency anemia when RDW >14.0% with low MCV 1. The elevated RDW (indicating anisocytosis) occurs because both small iron-deficient cells and larger older cells circulate simultaneously, while the low MCH reflects insufficient hemoglobin content per cell 2. This pattern is far more consistent with iron deficiency than thalassemia trait, which typically shows normal or only mildly elevated RDW despite low MCV/MCH 1, 2.
Alternative Diagnoses to Exclude
If iron studies are normal, consider:
- Thalassemia trait: Order hemoglobin electrophoresis, particularly in patients of Mediterranean, African, or Southeast Asian descent 4, 1
- Anemia of chronic disease: Assess for underlying inflammatory conditions; serum iron will be low but ferritin normal or elevated 3, 5
- Combined deficiencies: Measure vitamin B12 and folate levels if RDW is markedly elevated, as combined iron and folate deficiency can produce this pattern 4, 6
Investigation for Blood Loss Source
Once iron deficiency is confirmed, investigate the cause:
- Adult men and postmenopausal women: Require upper and lower gastrointestinal endoscopy to exclude malignancy, regardless of anemia severity 3, 4
- During upper endoscopy: Obtain small bowel biopsies to screen for celiac disease, which causes iron deficiency in 2-3% of cases 3
- Premenopausal women: Assess menstrual blood loss, but do not assume this is the sole cause without excluding gastrointestinal pathology if symptoms are present 3
- All patients: Document NSAID and aspirin use, which commonly causes occult gastrointestinal bleeding 3
Critical Pitfalls to Avoid
- Do not assume thalassemia based solely on low MCH—the markedly elevated RDW makes iron deficiency far more likely 2
- Do not overlook inflammation—ferritin cutoffs differ significantly (30 vs 100 μg/L) when CRP is elevated 1, 2
- Do not delay gastrointestinal evaluation once iron deficiency is confirmed—this is essential for detecting malignancy early 3, 4
- Do not rely on MCV alone—microcytosis may be absent in combined deficiencies, which is why the elevated RDW is such a valuable clue 3
Expected Response to Confirm Diagnosis
If iron deficiency is confirmed and treatment initiated, hemoglobin should rise ≥1 g/dL within 2 weeks, which retrospectively confirms the diagnosis 1. Lack of response within 2-4 weeks suggests non-compliance, ongoing blood loss, or malabsorption requiring intravenous iron 1.