What is the recommended treatment for severe anemia in an adult with end‑stage renal disease on regular hemodialysis who has normal ferritin, low serum iron, low transferrin saturation and mildly low mean corpuscular hemoglobin concentration?

Treatment for Severe Anemia in ESRD on Hemodialysis with Functional Iron Deficiency

This patient requires immediate intravenous iron supplementation followed by erythropoiesis-stimulating agent (ESA) therapy, as the severe anemia (Hb 6.5 g/dL) with low TSAT (18%) indicates functional iron deficiency that must be corrected before ESA therapy can be effective. 1

Immediate Management: Intravenous Iron Repletion

Initiate IV iron immediately with 100-125 mg at each hemodialysis session for 8-10 consecutive doses (total 800-1,000 mg). 1, 2, 3 This aggressive repletion is essential because:

• Your patient's TSAT of 18% is below the critical 20% threshold, indicating insufficient iron availability for erythropoiesis 1, 2
• Normal ferritin does NOT exclude functional iron deficiency in hemodialysis patients—the combination of low TSAT with normal ferritin is the hallmark of functional iron deficiency 2, 4, 5
• Oral iron is completely inadequate for hemodialysis patients due to ongoing blood losses from dialysis procedures, tubing retention, frequent phlebotomy, and poor intestinal absorption 2, 3

Critical pitfall to avoid: Do not withhold iron based on "normal" ferritin alone. 2 In ESRD patients on hemodialysis, iron deficiency is defined by TSAT ≤20% and/or ferritin <100 ng/mL (or <200 ng/mL in some guidelines). 1, 4 Your patient meets criteria with TSAT 18%.

Concurrent ESA Therapy Initiation

Start ESA therapy immediately alongside IV iron given the life-threatening hemoglobin of 6.5 g/dL. 1, 6 The recommended approach:

• Initial ESA dose: 50-100 Units/kg three times weekly intravenously (preferred route for hemodialysis patients) 6
• Target hemoglobin: Aim for 10-11 g/dL, NOT higher, as targeting >11 g/dL increases mortality, cardiovascular events, and stroke risk 1, 6
• Rationale for concurrent therapy: With Hb 6.5 g/dL, waiting for iron repletion alone would delay critical anemia correction and increase transfusion risk 1

Monitoring Strategy

Weekly hemoglobin monitoring until stable, then monthly once target is reached. 6 For iron parameters:

• Check TSAT and ferritin monthly during the repletion phase (while not receiving IV iron that week) 1
• Once stable, monitor iron parameters at least every 3 months 1, 2
• If individual IV iron doses are 200-500 mg, wait 7+ days before checking iron parameters for accuracy 1

Dose Adjustments Based on Response

If hemoglobin rises >1 g/dL in any 2-week period: Reduce ESA dose by 25% to avoid overshooting target. 6

If hemoglobin increases <1 g/dL after 4 weeks of ESA therapy: Increase ESA dose by 25%. 6

After completing initial 8-10 dose IV iron course:

• If TSAT remains ≤20% and/or ferritin <100 ng/mL, repeat another course of 100-125 mg weekly for 8-10 weeks 1, 2
• Once TSAT ≥20% and ferritin ≥100 ng/mL are achieved, transition to maintenance IV iron 25-125 mg weekly 1, 2

Upper Safety Limits: When to Stop IV Iron

Withhold IV iron when TSAT >50% and/or ferritin >800 ng/mL. 1, 2, 3 Hold for up to 3 months, then recheck parameters before resuming at a reduced dose (one-third to one-half of previous). 1

Important caveat: Recent hepatic MRI studies show high rates of iatrogenic iron overload in dialysis patients, with direct correlation between cumulative IV iron dose and hepatic iron stores. 1 Some experts now suggest stopping iron when ferritin exceeds 500 ng/mL due to insufficient evidence of benefit and potential cardiovascular toxicity from oxidative stress and hepcidin elevation. 1, 3

Transfusion Considerations

With Hb 6.5 g/dL and hematocrit 21.1%, assess for symptomatic anemia (chest pain, dyspnea, altered mental status, hemodynamic instability). 1 If symptomatic, transfusion may be necessary as a bridge while awaiting ESA/iron response, though the goal is to minimize transfusions to reduce alloimmunization risk. 1

Why This Patient Has Functional Iron Deficiency

The constellation of normal ferritin, low serum iron, and TSAT 18% with normal MCV/MCH indicates functional iron deficiency—adequate iron stores that cannot be mobilized for erythropoiesis. 2, 4, 5 This occurs in ESRD due to:

• Elevated hepcidin levels blocking iron release from stores 1, 4
• Chronic inflammation (ferritin is an acute-phase reactant) 2, 4
• Increased iron demand from any prior or planned ESA therapy 2, 4

The MCHC of 30.8 (low) further supports iron-restricted erythropoiesis despite normal ferritin. 5