Evaluation of Iron Studies
Iron deficiency should be confirmed by iron studies prior to investigation, with serum ferritin being the single most useful marker of iron deficiency anemia (IDA), though other tests like transferrin saturation can be helpful when a false-normal ferritin is suspected. 1
Interpretation of Iron Studies
- Serum ferritin is the most reliable indicator of iron stores, with values <30 ng/mL typically confirming absolute iron deficiency 1, 2
- Transferrin saturation (iron/total iron binding capacity × 100) less than 20% is indicative of iron deficiency, especially useful when inflammatory conditions may falsely elevate ferritin 2
- A therapeutic response to iron therapy (Hb rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even with equivocal iron studies 1
- In patients with chronic inflammatory conditions, higher ferritin cutoffs may be needed to diagnose iron deficiency 1
Diagnostic Categories
- Absolute iron deficiency anemia (AIDA): TSAT < 20%; ferritin < 30 ng/mL 1
- Functional iron deficiency anemia (FIDA): TSAT 20–50%; ferritin 30–800 ng/mL 1
- Normal MCV does not exclude iron deficiency - microcytosis is a late finding 3
Required Investigation
- In men and postmenopausal women with newly diagnosed IDA, gastroscopy and colonoscopy should generally be the first-line GI investigations 1, 4
- CT colonography is a reasonable alternative for those not suitable for colonoscopy 1
- Screening for celiac disease should be performed as it is found in 3-5% of IDA cases 1
- Urinalysis or urine microscopy should be included in initial investigation 1
- In cases with negative bidirectional endoscopy and either inadequate response to iron replacement therapy (IRT) or recurrent IDA, further investigation of the small bowel is recommended 1
- Capsule endoscopy is the preferred test for examining the small bowel in persistent or recurrent IDA 1
Management Approach
- All patients with confirmed IDA should receive iron supplementation to correct anemia and replenish body stores 1
- Oral iron (ferrous sulfate 200-325 mg daily or on alternate days) is typically first-line therapy 1, 2, 5
- Treatment should be continued for three months after correction of anemia to replenish iron stores 1
- Ascorbic acid enhances iron absorption and should be considered when response is poor 1
- Parenteral iron should be used when there is intolerance to at least two oral preparations, non-compliance, malabsorption, chronic inflammatory conditions (CKD, heart failure, IBD, cancer), or ongoing blood loss 1, 2
Follow-up Monitoring
- Once normalized, hemoglobin concentration and red cell indices should be monitored at three-month intervals for one year and then after a further year 1
- Additional oral iron should be given if hemoglobin or MCV falls below normal 1
- Further investigation is only necessary if hemoglobin and MCV cannot be maintained with supplementation 1
Special Considerations
- Intravenous iron may be more effective than oral iron in certain populations, such as those with chronic kidney disease 4
- Low-dose or alternate-day oral iron dosing may improve absorption and reduce side effects compared to traditional three-times-daily dosing 5
- In patients with elevated ferritin but low transferrin saturation, iron therapy may still be beneficial, particularly in those with chronic inflammatory conditions 1
Common Pitfalls
- Relying solely on hemoglobin and hematocrit without measuring iron status indicators can miss iron depletion before anemia develops 3
- Assuming normal MCV excludes iron deficiency - iron deficiency can present with normocytic indices 3
- Stopping iron therapy too soon after hemoglobin normalization, before iron stores are replenished 1
- Failing to investigate the underlying cause of IDA, particularly in men and postmenopausal women where GI malignancy is a concern 1, 6, 7
- Overlooking celiac disease as a potential cause of IDA 1