Intravenous Iron Therapy Thresholds Based on Iron Studies
Intravenous iron therapy is typically considered when serum ferritin is <100 ng/mL with transferrin saturation <20%, or when ferritin is between 100-800 ng/mL with transferrin saturation <20% (functional iron deficiency), particularly in patients receiving erythropoiesis-stimulating agents (ESAs). 1
Iron Deficiency Parameters by Clinical Context
Chronic Kidney Disease
- Absolute iron deficiency: ferritin <100 ng/mL and transferrin saturation <20% in non-dialysis and peritoneal dialysis patients; ferritin <200 ng/mL and transferrin saturation <20% in hemodialysis patients 1
- Functional iron deficiency: ferritin <800 ng/mL and transferrin saturation <20% 1
- Higher ferritin targets (>200 ng/mL) and transferrin saturation (>20%) are associated with better hemoglobin response and lower ESA requirements 1
Heart Failure
- Current guidelines define iron deficiency as ferritin <100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation <20% 1
- Recent evidence suggests that transferrin saturation <20% (with ferritin <400 ng/mL) is the more reliable indicator for IV iron benefit in heart failure patients 2
- IV iron in heart failure patients with these parameters improves exercise capacity, quality of life, and reduces hospitalizations 1
Cancer-Related Anemia
- Absolute iron deficiency: ferritin <30 ng/mL and transferrin saturation <15% 1
- Functional iron deficiency: ferritin <800 ng/mL and transferrin saturation <20% in patients receiving ESAs 1
- IV iron has superior efficacy to oral iron when used with ESAs in cancer patients 1
Special Considerations for High Ferritin States
- In inflammatory states (cancer, chronic kidney disease, heart failure), ferritin may be elevated as an acute phase reactant despite iron deficiency 1
- The DRIVE study demonstrated that IV iron can be beneficial in patients with ferritin 500-1200 ng/mL if transferrin saturation is <25% 1
- Safety concerns exist with IV iron administration when ferritin >800 ng/mL, though benefit may still occur with low transferrin saturation 1
- Consider monitoring for iron overload when ferritin exceeds 500 ng/mL, particularly with long-term therapy 3
Alternative Iron Status Markers
- Reticulocyte hemoglobin content (CHr <30 pg) may better predict response to IV iron than traditional markers 1, 4
- Percentage of hypochromic red cells and soluble transferrin receptor may be useful when ferritin and transferrin saturation results are discordant 4
Common Pitfalls
- Relying solely on ferritin without considering transferrin saturation may miss functional iron deficiency 2
- Inflammatory states falsely elevate ferritin, masking iron deficiency 1
- Using the same cutoffs across different clinical contexts leads to under-treatment 5
- Failure to reassess iron parameters after initiating therapy may result in iron overload 3
When evaluating for IV iron therapy, always consider the clinical context, presence of inflammation, and use of ESAs rather than applying rigid cutoffs universally. The decision to administer IV iron should balance the potential benefits against risks of iron overload, particularly in patients with elevated ferritin levels.