In anemic patients (hemoglobin <12 g/dL), what ferritin and transferrin saturation thresholds indicate the need for intravenous iron in cancer patients versus non‑cancer patients, and what are the recommended dosing regimens?

IV Iron Parameters and Dosing for Anemic Patients: Cancer vs Non-Cancer

In cancer patients on chemotherapy with anemia, initiate IV iron when ferritin is <100 ng/mL (absolute deficiency) or when TSAT <20% with ferritin 100-800 ng/mL (functional deficiency); in non-cancer patients with chronic kidney disease, use lower thresholds of ferritin <30 ng/mL or TSAT <20% with ferritin up to 500 ng/mL. 1

Cancer Patients (On Chemotherapy)

Iron Deficiency Definitions and Thresholds

Absolute Iron Deficiency:

• Ferritin <100 ng/mL (regardless of TSAT) 1
• Alternative definition: Ferritin <30 ng/mL with TSAT <20% 1
• These patients should receive IV iron monotherapy to correct deficiency 1

Functional Iron Deficiency:

• TSAT <20% AND ferritin 100-800 ng/mL 1
• Alternative range: TSAT 20-50% OR ferritin 30-800 ng/mL 1
• IV iron should be given before or during ESA therapy if ESAs are being considered 1
• IV iron monotherapy may be considered without ESA, though evidence is limited 1

Dosing Regimens for Cancer Patients

For Functional Iron Deficiency:

• 1000 mg total iron dose given as single dose or multiple doses according to product label 1

For Absolute Iron Deficiency:

• Dose according to approved product labels until correction of iron deficiency 1
• Continue until ferritin reaches ≥100 ng/mL and TSAT ≥20% 1

Critical Caveats for Cancer Patients

• Iron treatment should be limited to patients actively receiving chemotherapy 1
• In patients receiving cardiotoxic chemotherapy (anthracyclines), administer IV iron before or after chemotherapy (not same day) or at end of treatment cycle to avoid potential cardiotoxicity potentiation 1
• Do not administer IV iron during neutropenia due to increased infection risk 1
• High-molecular weight iron dextran (Dexferrum) is not recommended due to anaphylaxis risk 1

Upper Safety Limits for Cancer Patients

• Withhold iron if TSAT >50% OR ferritin >800 ng/mL 1
• The ferritin upper limit of 800 ng/mL represents a conservative threshold, though some guidelines suggest clinical judgment for ferritin >500 ng/mL 1

Non-Cancer Patients (Chronic Kidney Disease)

Iron Deficiency Definitions and Thresholds

Absolute Iron Deficiency:

• Ferritin <30 ng/mL (no TSAT requirement per KDIGO guidelines) 1
• This is a lower threshold than cancer patients due to different pathophysiology 1

Functional Iron Deficiency:

• TSAT ≤30% with ferritin ≤500 ng/mL (per KDOQI guidelines) 1
• Target goals: Achieve TSAT ≥20% and ferritin ≥100 ng/mL 2
• Many patients require TSAT 20-50% and ferritin 100-500 ng/mL for optimal response, especially if receiving erythropoietin 2

Dosing Regimens for Non-Cancer Patients

Loading Phase:

• 100-125 mg IV iron per session for 8-10 doses total 2
• Can be given up to three times weekly for hemodialysis patients 2

Maintenance Phase:

• 25-125 mg weekly, ranging from three times weekly to once every 2 weeks 2
• Total of 250-1000 mg iron within any 12-week period 2

Monitoring for Non-Cancer Patients

• Check TSAT and ferritin 7 days after final loading dose (not sooner, as earlier measurements are falsely elevated) 2
• During loading phase: Monitor iron parameters at least every 3 months, or monthly if not receiving regular IV iron 2
• After achieving target hemoglobin: Continue monitoring every 3 months 2

Upper Safety Limits for Non-Cancer Patients

• Immediately withhold iron if TSAT >50% OR ferritin >800 ng/mL 2
• Recheck parameters in 2-4 weeks 2
• When parameters normalize, resume at one-third to one-half of previous maintenance dose 2

Key Differences Between Populations

Ferritin Thresholds

• Cancer patients: Higher threshold (ferritin <100 ng/mL for absolute deficiency) because ferritin is an acute-phase reactant elevated by inflammation 1
• Non-cancer CKD patients: Lower threshold (ferritin <30 ng/mL) reflects true iron stores without confounding inflammation 1

Treatment Context

• Cancer patients: IV iron restricted to those on active chemotherapy 1
• Non-cancer CKD patients: IV iron appropriate regardless of dialysis status or erythropoietin use 2, 3, 4

Dosing Strategy

• Cancer patients: Typically single course of 1000 mg total 1
• Non-cancer CKD patients: Loading phase followed by ongoing maintenance therapy 2

Clinical Response Expectations

Cancer Patients:

• Hemoglobin response (≥2 g/dL increase) in approximately 10-30% when IV iron added to ESA therapy 1
• Maximal benefit seen with Hb <11 g/dL and ferritin <500 ng/mL 1, 5
• Response may occur as early as week 3 with ≥1.0 g/dL increase 5

Non-Cancer CKD Patients:

• Approximately 55% reach target Hb of 12 g/dL with IV iron alone (without erythropoietin) 4
• Mean Hb increase of 1.8 g/dL after 3 months of treatment 4
• If no response despite achieving TSAT ≥20% and ferritin ≥100 ng/mL, consider second 10-dose course before concluding iron-refractory 2

Common Pitfalls

• Ferritin misinterpretation in cancer: A ferritin of 60 ng/mL in a cancer patient may actually represent absolute deficiency due to inflammation elevating baseline ferritin 1
• Premature monitoring: Avoid measuring iron parameters within 7 days of IV iron administration, as circulating iron interferes with assays 2
• Hypophosphatemia: Asymptomatic hypophosphatemia occurs in approximately 46% of cancer patients receiving ferric carboxymaltose 5
• Infection risk: Meta-analysis shows 33% increased infection risk with IV iron; avoid during neutropenia in cancer patients 1