What lab results warrant IV iron replacement in patients with iron deficiency anemia, particularly those with chronic kidney disease, cancer, or inflammatory bowel disease?

Lab Results Warranting IV Iron Replacement

IV iron replacement is warranted when transferrin saturation (TSAT) is <20% and/or serum ferritin is below disease-specific thresholds, particularly in patients with chronic kidney disease (CKD), inflammatory bowel disease (IBD), chronic heart failure (CHF), or cancer, especially when hemoglobin is <10 g/dL or oral iron has failed. 1

Disease-Specific Laboratory Thresholds

Chronic Kidney Disease

• Absolute iron deficiency: TSAT <20% with ferritin <100 ng/mL (predialysis and peritoneal dialysis patients) or <200 ng/mL (hemodialysis patients) 1
• Functional iron deficiency: TSAT <20% even when ferritin is 100-800 ng/mL, particularly in patients receiving erythropoietin 1
• IV iron is indicated when these thresholds are met and hemoglobin remains <11-12 g/dL despite adequate erythropoietin dosing 1
• Upper safety limits: Maintain TSAT <50% and ferritin <800 ng/mL to avoid iron overload 1

Inflammatory Bowel Disease

• Primary indication: TSAT <20% and/or ferritin <100 μg/L in the presence of inflammation 1
• Strong recommendation for IV iron when:
  • Hemoglobin <10 g/dL (100 g/L) 1
  • Clinically active IBD present 1
  • Previous intolerance to oral iron 1
  • Need for erythropoiesis-stimulating agents 1
• Ferritin up to 100 μg/L may still reflect iron deficiency in inflammatory states 1
• Upper safety limits: TSAT >50% and ferritin >800 μg/L 1

Chronic Heart Failure

• Iron deficiency definition: Ferritin <100 μg/L and/or TSAT <20% 1
• IV iron is indicated for both absolute and functional iron deficiency meeting these criteria, as it provides prognostic benefit 1
• Oral iron should be avoided in CHF due to poor absorption from gut edema and lack of prognostic benefit 1

Cancer Patients

• General threshold: TSAT <20% and ferritin <100 μg/L 2, 3
• Iron deficiency affects 18-82% of cancer patients and warrants screening 3
• IV iron preferred over oral due to chronic inflammatory state and impaired absorption 2, 3

Key Diagnostic Considerations

Distinguishing Absolute vs. Functional Iron Deficiency

• Absolute iron deficiency: TSAT <20% with ferritin <100 ng/mL (or <30 ng/mL without inflammation) 1
• Functional iron deficiency: TSAT <20% despite ferritin 100-700 ng/mL, indicating inadequate iron mobilization from stores 1
• Inflammatory block: Abrupt ferritin increase with sudden TSAT drop; trial 50-125 mg IV iron weekly for 8-10 doses to differentiate 1

Impact of Inflammation on Interpretation

• Ferritin is an acute phase reactant and increases with inflammation, making TSAT more reliable in inflammatory conditions 1, 4
• In inflammatory states, ferritin up to 100 μg/L may still indicate iron deficiency 1
• TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency and is less affected by inflammation 5, 4, 2

Clinical Scenarios Requiring IV Iron

Mandatory IV Iron Indications

• Hemodialysis patients: Most require IV iron to maintain hemoglobin 11-12 g/dL due to dialyzer blood losses and impaired oral absorption 1, 6
• Hemoglobin <10 g/dL with iron deficiency: Regardless of underlying condition 1
• Oral iron failure: Inadequate response, intolerance, or contraindication to oral iron 5, 3
• Ongoing blood loss: Chronic bleeding conditions where oral iron cannot keep pace 3
• Pregnancy (2nd and 3rd trimesters): When iron deficiency is documented 3

Preferred IV Iron Situations

• Malabsorption conditions: Celiac disease, post-bariatric surgery, atrophic gastritis 3
• Active IBD: Oral iron may exacerbate disease activity and is poorly absorbed 1
• Chronic inflammatory conditions: CKD, CHF, cancer where hepcidin elevation blocks oral iron absorption 2, 3, 6

Monitoring Parameters

Pre-Treatment Assessment

• Baseline TSAT and ferritin required to confirm iron deficiency, determine dosing, and avoid overload 5
• Complete blood count with hemoglobin 1
• C-reactive protein to assess inflammatory state 1

Post-Treatment Monitoring

• IBD patients: Monitor every 3 months for at least 1 year after correction, then every 6-12 months 1
• Re-treatment threshold: Ferritin drops below 100 μg/L or hemoglobin below 12-13 g/dL (gender-dependent) 1
• CKD patients: Maintain TSAT ≥20% and ferritin ≥100 ng/mL 1
• Response assessment: Check iron parameters 4-8 weeks after last infusion; expect hemoglobin increase within 1-2 weeks 5

Common Pitfalls to Avoid

• Do not rely solely on ferritin in inflammatory conditions: Use TSAT as the primary marker when inflammation is present 4, 2
• Do not withhold IV iron based on "normal" ferritin: Ferritin 100-300 μg/L with TSAT <20% indicates functional iron deficiency requiring treatment 1
• Do not use oral iron in hemodialysis patients: Elevated hepcidin prevents intestinal absorption 6
• Do not exceed safety thresholds: Stop IV iron if TSAT >50% or ferritin >800 ng/mL chronically 1
• Do not assume anemia is solely from iron deficiency in CKD: Multiple mechanisms contribute; detailed hematological investigation needed 1