Iron Infusion Thresholds
Intravenous iron infusion is warranted when ferritin is <100 ng/mL with transferrin saturation <20%, or when ferritin is <30 ng/mL regardless of transferrin saturation in the setting of anemia requiring treatment. 1
Absolute Iron Deficiency Thresholds
Ferritin <30 ng/mL with transferrin saturation <15% defines absolute iron deficiency and warrants IV iron supplementation. 1 This represents the most sensitive and specific threshold for identifying true iron depletion. 1
- In the presence of inflammation (C-reactive protein >5 mg/L), the ferritin threshold increases to <100 ng/mL because ferritin is an acute-phase reactant that can be falsely elevated. 1
- These patients should receive IV iron regardless of hemoglobin level if they are symptomatic or undergoing treatment that will worsen anemia. 1, 2
Functional Iron Deficiency Thresholds
Ferritin <800 ng/mL AND transferrin saturation <20% defines functional iron deficiency in patients on erythropoiesis-stimulating agents or chemotherapy. 1 This scenario indicates iron stores exist but cannot be mobilized effectively for red cell production.
- IV iron has superior efficacy over oral iron in this setting and should be strongly considered. 1
- The NCCN guidelines specifically state that ferritin <800 ng/mL with TSAT <20% warrants IV iron supplementation in cancer patients receiving chemotherapy. 1
Context-Specific Thresholds
Perioperative/Colorectal Surgery
- Target preoperative hemoglobin of ≥130 g/L should be pursued. 1
- Ferritin <100 µg/L with transferrin saturation <20% in the presence of inflammation indicates need for IV iron. 1
- Oral iron is ineffective in inflammatory bowel disease due to hepcidin activation; IV iron overcomes this problem. 1
Chronic Kidney Disease
- Ferritin ≤100 ng/mL OR transferrin saturation ≤20% triggers IV iron initiation. 1
- Stop IV iron when ferritin ≥800 ng/mL AND TSAT ≥20%, OR when TSAT ≥40%. 1
- These thresholds apply to both dialysis-dependent and non-dialysis-dependent CKD patients. 1, 3
Heart Failure
- Transferrin saturation is more prognostically significant than ferritin in heart failure patients. 4
- Low TSAT (typically <20%) is associated with adverse outcomes regardless of ferritin level. 4
- Current ID definitions (ferritin <100 or 100-299 ng/mL with TSAT <20%) should guide treatment decisions. 4
Dosing Considerations
Total iron dose calculation:
- 1500 mg for patients with hemoglobin 7-10 g/dL and weight <70 kg. 2
- 2000 mg for patients with hemoglobin 7-10 g/dL and weight ≥70 kg. 2
- Typically administered as 1-2 infusions depending on formulation. 2
Formulation-specific limits:
- Iron sucrose: 200-300 mg per dose. 2, 3
- Ferric carboxymaltose: up to 1000 mg per dose (preferred for higher doses). 2
- Iron dextran: requires test dose due to anaphylaxis risk. 2, 5
Upper Safety Limits
Stop IV iron when:
- Transferrin saturation >50% 1, 2, 6
- Ferritin >800 ng/mL (some sources suggest 1000 ng/mL as absolute upper limit) 1, 2, 6
These upper limits prevent iron overload and potential toxicity, though evidence suggests harm primarily occurs at dramatically higher ferritin levels. 1
Important Clinical Caveats
- Do not administer IV iron in the presence of active infection. 2
- Ferritin alone is unreliable in inflammatory states; always interpret with transferrin saturation and clinical context. 1, 7
- The scenario of ferritin >800 ng/mL with TSAT <20% has become increasingly common with multiple comorbidities, and limited evidence suggests IV iron may still benefit selected patients, though safety data are insufficient. 1, 7
- Reticulocyte hemoglobin content ≥31.2 pg predicts better response to IV iron, though lower values do not preclude benefit. 8
- Oral iron absorption is only 40-60 mg per day and is poorly tolerated; IV iron is more effective for rapid repletion. 1, 6