Treatment of Iron Deficiency with Low Ferritin and High Transferrin
Oral iron supplementation at 100-200 mg elemental iron daily is the first-line treatment for iron deficiency with low ferritin and high transferrin (indicating depleted iron stores), unless the patient has active inflammatory disease, severe anemia (hemoglobin <100 g/L), or previous intolerance to oral iron—in which cases intravenous iron should be used instead. 1
Diagnostic Confirmation
Low ferritin with high transferrin (or high total iron-binding capacity/TIBC) is the classic laboratory pattern of iron deficiency:
- Ferritin <30 µg/L confirms depleted iron stores in patients without inflammation 1
- High transferrin/TIBC indicates the body's compensatory response to increase iron-binding capacity when iron is scarce 1
- A transferrin saturation <20% further confirms inadequate iron delivery to tissues 1
- In the presence of inflammation, ferritin up to 100 µg/L may still indicate iron deficiency 1
Treatment Algorithm
First-Line: Oral Iron Supplementation
For patients with clinically inactive disease and mild or no anemia:
- Dosage: 100-200 mg elemental iron daily in divided doses 1
- Alternate-day dosing may improve absorption and reduce gastrointestinal side effects 1
- Common formulations include ferrous sulfate 324 mg tablets (containing 65 mg elemental iron) 2
- Expected gastrointestinal side effects include constipation, diarrhea, and nausea 1
Indications for Intravenous Iron (First-Line)
Switch to IV iron when any of the following are present:
- Clinically active inflammatory bowel disease or other inflammatory conditions 1
- Hemoglobin <100 g/L (severe anemia) 1
- Previous intolerance to oral iron 1
- Failure to respond to oral iron after adequate trial 1
- Patients requiring erythropoiesis-stimulating agents 1
IV iron formulations and administration:
- Ferric carboxymaltose allows rapid administration of large single doses (up to 1 g elemental iron) over 15 minutes 1
- Iron sucrose and ferric gluconate require multiple administrations 1
- Hypersensitivity reactions are rare (<1:250,000 with modern formulations) 1, 3
- Avoid high molecular weight iron dextran due to higher reaction risk 1
Monitoring Response to Treatment
Reassess iron status and hemoglobin after 8-10 weeks of oral iron therapy (not earlier, as ferritin levels are falsely elevated immediately after IV iron) 1:
- Hemoglobin should increase by 10-20 g/L with adequate response 1
- Ferritin should rise toward normal range (>30 µg/L without inflammation) 1
- Transferrin saturation should increase above 20% 1
If no response after 2-4 weeks of oral therapy:
- Consider switching to IV iron 1, 3
- Investigate for ongoing blood loss or malabsorption 3, 4
- Test for Helicobacter pylori and celiac disease, both common causes of refractory iron deficiency 3
Treatment Goals
Target iron parameters:
- Ferritin >30 µg/L (or >100 µg/L in inflammatory conditions) 1
- Transferrin saturation >20% 1
- Hemoglobin normalization to age- and sex-appropriate levels 1
Critical Pitfalls to Avoid
- Do not supplement iron when ferritin is normal or elevated without clear indication, as this is potentially harmful 1
- Do not rely solely on ferritin in inflammatory states, as it is an acute-phase reactant and may be falsely elevated despite true iron deficiency 1
- Do not check ferritin immediately after IV iron administration, as levels will be artificially elevated for 8-10 weeks 1
- Do not continue oral iron indefinitely without monitoring response, as approximately 50% of patients have poor adherence due to side effects 3
Underlying Cause Investigation
Identify and treat the source of iron loss:
- Recurrent blood loss accounts for 94% of iron deficiency cases 3
- In men and postmenopausal women, perform bidirectional endoscopy to evaluate for gastrointestinal bleeding 3
- In premenopausal women with heavy menstrual bleeding, treat the bleeding source while providing iron supplementation 3
- Test for H. pylori and celiac disease as both commonly cause iron deficiency 3