What is the management for abnormal serum ferritin levels?

Management of Abnormal Serum Ferritin Levels

Low Ferritin (Iron Deficiency)

For iron deficiency, use a ferritin cut-off of <45 µg/L in anemic patients, or <30 µg/L in healthy adults without anemia, to guide treatment decisions. 1, 2

Diagnostic Thresholds

• Adults >15 years: Ferritin <30 µg/L indicates iron deficiency 2
• Anemic patients: Ferritin <45 µg/L has optimal sensitivity/specificity 1
• Athletes (females): Ferritin <35 µg/L defines deficiency 1
• Children 12-15 years: Use cut-off of 20 µg/L 2
• Children 6-12 years: Use cut-off of 15 µg/L 2

Critical caveat: In inflammatory conditions (check C-reactive protein), iron deficiency can exist with ferritin 45-100 µg/L; confirm with transferrin saturation <20%, soluble transferrin receptor, or reticulocyte hemoglobin 1, 3

Treatment Algorithm for Low Ferritin

Step 1: Identify and treat underlying cause 1, 3

• Evaluate dietary iron intake
• Review menstrual blood losses in premenopausal women
• Screen for gastrointestinal bleeding sources
• Test for Helicobacter pylori infection
• Consider celiac disease, atrophic gastritis, or bariatric surgery history

Step 2: Initiate oral iron therapy (first-line) 1, 2, 3

• Dose: Ferrous sulfate 325 mg daily OR 28-50 mg elemental iron daily 1, 2
• Alternative dosing: Every-other-day administration may improve tolerance 3
• Timing: Take on empty stomach for optimal absorption; if not tolerated, take with meals 1
• Enhancers: Co-administer 500 mg vitamin C or take with meat protein 1
• Avoid: Tea, coffee, calcium, and fiber around dosing times 1
• Recheck labs: Repeat hemoglobin, ferritin after 8-10 weeks 2

Step 3: Switch to intravenous iron if: 1, 3, 4

• Oral iron intolerance (nausea, abdominal pain, constipation)
• Malabsorption (celiac disease, post-bariatric surgery, atrophic gastritis)
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss requiring rapid repletion
• Pregnancy (second and third trimesters)
• Failure to respond to oral iron after adequate trial

Special Populations

Chronic Kidney Disease (Hemodialysis): 1

• Target ferritin >200 ng/mL (lower limit) to reduce ESA requirements 1
• Maintain transferrin saturation >20% 1
• Monitor ferritin every 3 months during maintenance 1
• Even with elevated ferritin (500-1200 ng/mL): Consider IV iron if transferrin saturation <25% and hemoglobin suboptimal on high ESA doses 1

Celiac Disease: 1

• Ensure strict adherence to gluten-free diet to improve iron absorption
• Start with oral iron supplementation
• Progress to IV iron if stores do not improve

Athletes: 1

• Screen females twice yearly, males once yearly
• Recommend diet rich in heme iron (red meat, seafood)
• Oral supplementation above RDA after medical consultation
• Avoid parenteral iron unless malabsorption documented

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Elevated Ferritin (Iron Overload)

For hemochromatosis, target ferritin of 50 µg/L during induction phlebotomy, then maintain 50-100 µg/L during maintenance phase. 1

Phlebotomy Protocol for Hemochromatosis

Induction Phase: 1

• Volume: 400-500 mL per session
• Frequency: Weekly or every 2 weeks
• Target: Ferritin <50 µg/L
• Monitoring: Check ferritin monthly (or every 4th phlebotomy); when <200 µg/L, check every 1-2 sessions 1
• Stop criteria: If hemoglobin <11 g/dL, discontinue and reassess 1
• Reduce frequency: If hemoglobin <12 g/dL 1

Maintenance Phase: 1

• Target: Ferritin 50-100 µg/L (stricter) or <200 µg/L (women)/<300 µg/L (men) for elderly patients 1
• Frequency: Every 1-4 months based on ferritin rise (average ~100 µg/L per year) 1
• Monitoring: Check ferritin every 6 months 1

Dietary Modifications for Iron Overload

1

• Avoid: Iron supplements, iron-fortified foods, supplemental vitamin C (especially before depletion)
• Limit: Red meat consumption, alcohol intake (restrict during depletion; abstain if cirrhosis)
• Caution: Avoid raw/undercooked shellfish and seawater wound exposure (risk of Vibrio vulnificus infection in iron overload)
• Important: Dietary modifications do NOT substitute for phlebotomy therapy

Chelation Therapy (Alternative to Phlebotomy)

Deferoxamine for chronic iron overload when phlebotomy not feasible: 5

• Subcutaneous route (preferred): 1000-2000 mg (20-40 mg/kg/day) over 8-24 hours via continuous infusion pump
• Intravenous route: 20-40 mg/kg/day (children) or 40-50 mg/kg/day (adults) over 8-12 hours, 5-7 days/week
• Maximum: Do not exceed 15 mg/kg/hour infusion rate
• Pediatric limit: Average doses should not exceed 40 mg/kg/day until growth cessation 5
• Adult limit: Average doses should not exceed 60 mg/kg/day 5

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Monitoring Pitfalls

• False-normal ferritin: Ferritin is an acute phase reactant; check CRP to exclude inflammation masking true iron deficiency 1, 2
• Transferrin saturation: May remain elevated (>50%) in hemochromatosis even when ferritin is at target; this does not require additional intervention unless symptomatic 1
• Over-treatment risk: Ferritin <20 µg/L can cause symptomatic iron deficiency even in hemochromatosis patients; avoid excessive phlebotomy 1
• Hemodialysis patients: Safety of IV iron with ferritin >500 ng/mL is uncertain; balance potential hemoglobin benefit against unknown risks 1