Iron Transfusion Indications Based on Laboratory Values
Iron transfusion (intravenous iron) is indicated when serum ferritin is <100 ng/mL with transferrin saturation <20%, or when ferritin is <30 ng/mL regardless of transferrin saturation in patients without inflammation. The specific thresholds vary by clinical context and presence of inflammation.
Diagnostic Thresholds by Clinical Context
Patients Without Inflammation
- Absolute iron deficiency: Ferritin <30 ng/mL or transferrin saturation <16-20% 1
- These patients have depleted iron stores and impaired iron delivery to bone marrow 1
Patients With Inflammation (IBD, CKD, Cancer, Heart Failure)
- Iron deficiency: Ferritin <100 ng/mL, regardless of transferrin saturation 1
- Functional iron deficiency: Ferritin 100-800 ng/mL AND transferrin saturation <20% 1
- Ferritin acts as an acute-phase reactant during inflammation, making values between 30-100 ng/mL suggestive of combined true iron deficiency and anemia of chronic disease 1
Disease-Specific Criteria
Chronic Kidney Disease (CKD)
- Predialysis and peritoneal dialysis patients: Ferritin ≤100 ng/mL AND transferrin saturation ≤20% 2
- Hemodialysis patients: Ferritin ≤200 ng/mL AND transferrin saturation ≤20% 1, 2
- Intravenous iron is preferred over oral iron for all CKD stage 5D (dialysis) patients 2
Heart Failure
- Iron deficiency definition: Ferritin <100 ng/mL OR ferritin 100-300 ng/mL with transferrin saturation <20% 1, 3
- Intravenous iron is recommended to increase exercise capacity regardless of anemia presence 1, 3
- Transferrin saturation has stronger prognostic significance than ferritin in heart failure outcomes 4
Inflammatory Bowel Disease
- Without inflammation: Ferritin <30 ng/mL or transferrin saturation <16% 1
- With inflammation: Ferritin up to 100 ng/mL may indicate iron deficiency 1
- Intravenous iron is first-line for clinically active IBD, hemoglobin <100 g/L, or previous oral iron intolerance 1
Cancer and Chemotherapy-Induced Anemia
- Functional iron deficiency: Ferritin <800 ng/mL AND transferrin saturation <20% 1
- Absolute iron deficiency: Ferritin <30 ng/mL and transferrin saturation <15% 1
- Intravenous iron with erythropoiesis-stimulating agents is recommended for functional iron deficiency 1
Route of Administration Decision
Intravenous Iron is Preferred When:
- Clinically active inflammatory disease (IBD, heart failure) 1
- Hemoglobin <100 g/L (10 g/dL) 1
- Previous intolerance to oral iron 1, 3
- Need for erythropoiesis-stimulating agents 1
- CKD patients on hemodialysis 2
- Functional iron deficiency in cancer patients 1
Oral Iron May Be Considered When:
- Mild anemia with clinically inactive disease 1
- No previous oral iron intolerance 1
- Ferritin <30 ng/mL without inflammation 5
Important Caveats
Ferritin limitations: Ferritin is an acute-phase reactant and can be falsely elevated during inflammation, infection, or malignancy 1, 6. A patient with ferritin >500 ng/mL but transferrin saturation <25% may still respond to intravenous iron if functionally iron deficient 1.
Transferrin saturation is more reliable: In inflammatory states, transferrin saturation <20% is a more sensitive indicator of iron-restricted erythropoiesis than ferritin alone 1, 4.
Upper ferritin threshold: Some guidelines support intravenous iron administration even when ferritin is 500-1200 ng/mL if transferrin saturation remains <25%, particularly in CKD patients on high-dose erythropoietin 1.
Response assessment: Patients on oral iron should show a 1-2 g/dL hemoglobin increase within 2-4 weeks; failure to respond warrants switching to intravenous iron or investigating for continued blood loss 5, 7.
Avoid iron supplementation: Do not administer iron during active infection due to concerns about promoting bacterial growth 1.