Iron Deficiency: Diagnosis and Management
The combination of low MCH, low MCHC, and high RDW is highly specific for iron deficiency, and you must confirm this with serum ferritin testing (<30 μg/L confirms deficiency) followed by mandatory gastrointestinal evaluation in all adult men and post-menopausal women regardless of hemoglobin level. 1
Understanding This Laboratory Pattern
High RDW is a specific indicator of iron deficiency, reflecting heterogeneous red cell populations with varying sizes as iron stores become depleted 1. RDW shows larger values concomitant with the development of iron deficiency, even before frank anemia develops 2.
Low MCH indicates reduced hemoglobin content per red cell, which occurs early in iron deficiency before frank anemia develops 1. MCH is actually more reliable than MCV for detecting iron deficiency because it decreases in both absolute and functional iron deficiency 3.
Low MCHC further supports iron deficiency, as it reflects decreased hemoglobin concentration within red cells 4, 5.
This triad has strong diagnostic accuracy: RDW sensitivity of 72-77% for iron deficiency, MCH with ROC curve of 0.67-0.72, and MCHC with ROC curve of 0.71 6, 4, 5.
Essential Diagnostic Workup
Confirm Iron Deficiency
Serum ferritin is the single most powerful test for iron deficiency and must be obtained first 7, 3.
Obtain C-reactive protein (CRP) simultaneously to interpret ferritin correctly, as inflammation elevates ferritin and can mask true iron deficiency 1.
Transferrin saturation <30% supports the diagnosis of iron deficiency 7, 1.
Screen for Celiac Disease
- Celiac disease screening is mandatory, as 2-3% of patients with iron deficiency have this diagnosis 1, 3.
Investigation for Underlying Causes
Who Requires GI Evaluation
All adult men and post-menopausal women with confirmed iron deficiency require gastrointestinal evaluation regardless of hemoglobin level or symptom presence 1, 3.
Pre-menopausal women without GI symptoms may have menstrual blood loss as the cause, but GI evaluation should still be considered if iron deficiency is severe or refractory 7.
Comprehensive GI Workup
Upper endoscopy with small bowel biopsies: 30-50% will have an upper GI source; small bowel biopsies must be obtained to screen for celiac disease 1, 3.
Colonoscopy or CT colonography is mandatory even if an upper GI source is found, because dual pathology occurs in approximately 10% of patients 1, 3.
Stool examination for ova and parasites should be performed to exclude hookworm infection 3.
Common GI Causes to Exclude
- Colorectal cancer or polyps 3
- NSAID use (stop if possible) 7, 3
- Gastric cancer 7
- Angiodysplasia 7, 3
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis) 7, 3
- Previous gastrectomy 7
Treatment Approach
Initiate oral iron supplementation once iron deficiency is confirmed by ferritin testing 1. New evidence suggests intermittent dosing is as effective as daily dosing with fewer side effects 8.
For patients who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred 1, 8.
Continue iron for 3-6 months after hemoglobin normalizes to replete stores 1.
A good response to iron therapy (hemoglobin rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency 3.
Critical Pitfalls to Avoid
Never assume normal or near-normal hemoglobin excludes significant pathology—mild anemia or pre-anemic iron deficiency can indicate serious underlying disease including malignancy 1, 3.
Avoid empiric iron therapy without confirming iron deficiency with ferritin, as this can cause harm in thalassemia patients and delays proper diagnosis 1.
Do not rely on dietary history alone as the cause of iron deficiency—borderline deficient diets are common, but a full GI investigation is still required 7.
Do not let NSAID use or anticoagulants deter investigation—these should be noted and stopped when possible, but GI evaluation must still proceed 7.