At what level does iron toxicity occur?

Iron Toxicity Levels and Management

Iron toxicity occurs at serum iron concentrations of ≥350 μg/dL with symptoms or ≥500 μg/dL without symptoms, with severe toxicity typically occurring at ingestions of ≥60 mg/kg of elemental iron. 1, 2

Diagnostic Thresholds for Iron Toxicity

Serum Iron Concentration Thresholds

• Serum iron concentration ≥350 μg/dL with symptoms indicates toxicity requiring treatment 1
• Serum iron concentration ≥500 μg/dL without symptoms indicates toxicity requiring treatment 1
• Serum iron concentration ≤300 μg/dL between 2-4 hours post-ingestion with only minor GI symptoms suggests low risk for developing subsequent toxicity (negative predictive value 100%) 1

Ingested Dose Thresholds

• Acute iron ingestions >60 mg/kg of elemental iron are potentially serious 2
• Ingestion of ≥28 mg/kg of elemental iron has been identified as the minimum cut-off triggering serious toxicity and need for chelation therapy in children 3
• Severe toxicity has been reported with ingestions of 100-130 mg/kg of elemental iron 4, 2

Clinical Manifestations of Iron Toxicity

Acute Iron Toxicity Stages

1. Gastrointestinal Phase (0-6 hours)

   • Vomiting, diarrhea, abdominal pain, gastrointestinal bleeding 2, 5

2. Apparent Stabilization Phase (6-24 hours)

   • Deceptive improvement in symptoms 5

3. Systemic Toxicity Phase (24-72 hours)

   • Metabolic acidosis, shock, coagulopathy, hepatic failure 2, 5

4. Late Complications (2-8 weeks)

   • Gastrointestinal scarring, pyloric stenosis, hepatic cirrhosis 5

Chronic Iron Overload Manifestations

• Chronic fatigue, joint pain, abdominal pain 6
• Skin pigmentation changes 6
• Endocrine manifestations: diabetes mellitus, hypogonadism 6
• Cardiac manifestations: cardiomyopathy, dysrhythmias, heart failure 6, 7
• Hepatic manifestations: elevated liver enzymes, progressive fibrosis, cirrhosis, hepatocellular carcinoma 6

Management of Iron Toxicity

Acute Iron Poisoning Management

1. Gastrointestinal Decontamination

   • Gastric lavage with sodium bicarbonate solution for recent ingestions 2, 4
   • Whole-bowel irrigation with polyethylene glycol-electrolyte solution for large ingestions or when tablets are visible on abdominal radiography 2

2. Chelation Therapy

   • Deferoxamine is indicated for:
     • Serum iron >500 μg/dL
     • Serum iron >350 μg/dL with symptoms
     • Estimated ingestion >60 mg/kg with symptoms 2, 5
   • Dosing: continuous IV infusion at 15 mg/kg/hr (maximum 6 g/24 hr) 2, 4

3. Supportive Care

   • Fluid resuscitation for shock
   • Correction of metabolic acidosis
   • Blood component replacement for hemorrhage 5

4. Extracorporeal Removal

   • Hemodialysis may be beneficial in severe cases with massive overdose and life-threatening toxicity 4

Chronic Iron Overload Management

1. Phlebotomy

   • First-line treatment for hereditary hemochromatosis 6

2. Iron Chelation Therapy

   • Used to treat secondary iron overload 6
   • Options include deferoxamine, deferiprone, and deferasirox

3. Monitoring

   • Regular assessment of iron status (ferritin and hemoglobin) in patients on long-term parenteral nutrition 7
   • MRI with quantitative assessment of iron content for cardiac and hepatic iron load 6

Special Considerations

Pediatric Considerations

• Children aged 9-18 months are at highest risk for iron deficiency due to rapid growth and frequently inadequate dietary iron intake 7
• In children with hemoglobinopathy receiving transfusion and chelation, cardiac iron overload (T2* <20 ms) typically occurs after 10 years of age 7
• Preterm and low-birthweight infants are at greater risk for iron deficiency than full-term infants 7

Parenteral Iron Administration

• Iron supplementation should preferentially be given enterally rather than parenterally when tolerated 7
• Routine parenteral iron supplements should be given at a dose of 200-250 μg/kg/day in preterm infants and 50-100 μg/kg/day (maximum 5 mg/day) in infants and children 7
• Systemic iron toxicity with hepatocellular damage has been observed in a pediatric patient receiving 16 mg/kg of iron sucrose 7

Important Clinical Pitfalls

• Delayed diagnosis of iron overload can lead to irreversible organ damage 6
• Treatment monitoring is crucial to assess treatment success and prevent cardiac complications 6
• Hepatocellular carcinoma risk persists in cirrhotic patients even after adequate iron removal, necessitating continued surveillance 6
• Early treatment before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 6