Iron Poisoning: The Five Stages and Deferoxamine
For most of the twentieth century, iron tablets were among the leading causes of poisoning death in small children — not because they are exotic, but because they are everywhere: sugar-coated, brightly coloured, and left within reach as a mother's prenatal supplement. A toddler mistakes them for sweets and swallows a handful. What follows is a slow, staged illness with a treacherous quiet spell in the middle — and a striking antidote that reaches into the blood and pulls the loose iron out.
A 2-year-old is brought to the emergency department after her mother found the prenatal vitamin bottle open and pills scattered on the floor. The child has vomited three times — once with a streak of blood — and passed a loose, dark stool. She is irritable but alert. A plain abdominal X-ray shows a scatter of dense, radio-opaque tablets in the stomach. The mother is reassured when, an hour later, the vomiting settles and the girl seems brighter — but the toxicologist is not. This is the deceptive lull, the second of five stages, and beneath the calm the absorbed iron is already seeding a metabolic acidosis. The team starts whole-bowel irrigation and draws a serum iron level, timed to the ingestion, to decide whether she needs the antidote.
Why iron is a poison
Iron injures in two waves: first the gut wall it touches, then every cell it reaches. In the lumen, concentrated iron salts are directly corrosive: they burn the gastrointestinal mucosa, producing vomiting, haematemesis, diarrhoea and abdominal pain, and can strip the lining enough to bleed. But the deeper danger is systemic. Absorption is normally throttled by the gut, yet a large overdose overwhelms that control, and the blood's iron-carrier protein transferrin becomes saturated. Iron that exceeds transferrin's binding capacity circulates as free iron — and free iron is a ferocious catalyst of free-radical (oxidative) reactions. It drives lipid peroxidation of cell membranes, poisons mitochondria so cells can no longer make ATP, and forces anaerobic metabolism, producing a lactic (metabolic) acidosis. The liver, receiving the first and highest load through the portal vein, and the vasculature are hit hardest. This is why iron is best thought of not as a stomach irritant but as a cellular poison — a small heavy-metal-like toxin that wrecks the mitochondrion.
The number that matters is elemental iron, not the tablet's total weight. A 325 mg tablet of ferrous sulfate is not 325 mg of iron — the salt is mostly its anion. Different iron salts carry very different fractions of usable (elemental) iron: ferrous fumarate is about a third elemental iron, ferrous sulfate roughly a fifth, and ferrous gluconate only about an eighth. Toxicity is judged by milligrams of elemental iron per kilogram of body weight: below roughly 20 mg/kg is usually benign, whereas ingestions above about 40–60 mg/kg threaten serious systemic poisoning. The same principle governs the therapeutic doses in the Haematology chapter, where oral iron is prescribed for iron-deficiency anaemia — the very supplement bottle a curious child empties is the source of the poisoning here.
Think of transferrin as a fleet of taxis that safely escorts iron through the blood, never letting a passenger wander loose. In an overdose the taxis are all full within minutes, and the extra iron is left to roam the streets on foot — unescorted free iron, colliding with everything and starting fires (free radicals) wherever it goes. The antidote, deferoxamine, is a tow-truck sent out specifically for those stranded, unescorted passengers: it clamps onto free iron only, leaving the taxi-bound iron and the body's essential iron (in haemoglobin and enzymes) untouched, and hauls the captured iron out through the kidneys.
The five clinical stages
Iron poisoning does not unfold all at once — it moves through five phases, and the second is a trap. The classic teaching divides the course into five overlapping stages defined by time and mechanism. The single most important idea is the second stage: an apparent recovery, a quiet window in which the corrosive gut symptoms settle and a child can look deceptively well — while absorbed iron is quietly driving a worsening cellular acidosis underneath. Sending such a patient home during this lull is a well-described disaster.
A child who was vomiting, then stops and looks well a few hours after an iron ingestion has not necessarily recovered — they may have entered the latent second stage. The reassuring interval is exactly when the absorbed iron is committing its systemic damage. Serial pH / lactate and a timed serum iron level, not the child's outward appearance, tell you where the poisoning is heading. "Looks better" is not "is better" in iron overdose.
- Iron is corrosive to the GI mucosa; absorbed free iron is a mitochondrial/cellular poison driving lactic acidosis.
- Toxicity is measured in elemental iron per kg — not tablet weight; salts differ (fumarate ≈ ⅓, sulfate ≈ ⅕, gluconate ≈ ⅛).
- Free iron saturates transferrin, then catalyses free-radical damage and mitochondrial injury.
- The five stages: (1) GI, (2) latent/apparent recovery, (3) shock & acidosis, (4) hepatic failure, (5) late strictures.
- The second (latent) stage is a trap — apparent recovery while systemic poisoning advances underneath.
Assessment: levels and the X-ray
Two investigations anchor the workup. The first is a serum iron level, but its value depends entirely on timing: peak absorption is usually around 4–6 hours post-ingestion, so a level drawn too early can be falsely low and one drawn very late can miss the peak after iron has redistributed into tissues. A level measured at the right window helps grade severity — very high levels correlate with the shock/acidosis stage. The second is a plain abdominal X-ray: many iron tablets are radio-opaque and appear as a scatter of dense pills, confirming ingestion, estimating the burden, and guiding decontamination. A negative film does not exclude poisoning — chewable, liquid or fully dissolved preparations may not show — but visible tablets are a strong indication to clear the gut. More useful than any single number is the metabolic picture: a rising lactate and a widening metabolic acidosis mark a patient who is deteriorating regardless of a reassuring appearance.
Management: decontamination and the antidote
Start with a high-yield fact: activated charcoal does not bind iron. This is one of the classic exceptions on every toxicology exam. Activated charcoal — the workhorse of poisoning decontamination — adsorbs organic molecules poorly matched to a small metal ion, so it is useless for iron. Instead, when there is a large ingestion or visible tablets on X-ray, the decontamination of choice is whole-bowel irrigation with polyethylene glycol solution, which physically flushes undissolved tablets through the gut before they can be absorbed. This connects directly to the Decontamination chapter, which lists iron alongside lithium, lead and drug packets as the settings where charcoal fails and whole-bowel irrigation earns its place. Around this, care is aggressively supportive: fluid resuscitation for corrosive GI losses and shock, correcting the metabolic acidosis, and managing coagulopathy and hepatic failure as they appear.
The antidote is deferoxamine — a chelator built to grab free iron. Deferoxamine is a chelating agent with an extraordinary affinity for ferric iron. Given by intravenous infusion, it binds free (unbound) iron in the plasma to form a stable complex, ferrioxamine, which the kidneys then excrete in the urine. Crucially it targets the loose, toxic iron while sparing iron already safely held in transferrin, haemoglobin and cytochromes — so it detoxifies without stripping the body of essential iron. A classic (if inconsistent) clue that chelation is working is urine that turns a reddish "vin rosé" colour as ferrioxamine is excreted. Deferoxamine is reserved for genuine severe toxicity — shock, a significant metabolic acidosis, a high serum iron level, or persistent/serious systemic symptoms — not for the well child with a trivial ingestion. Its main dose-limiting hazards are hypotension if infused too fast and, on prolonged use, a risk of pulmonary toxicity (ARDS). This places deferoxamine in the same family taught in the Heavy-metals & Chelation chapter — alongside dimercaprol, EDTA and DMSA (succimer) — each a molecular claw matched to a particular metal, and it belongs to the antidote toolkit of the Enhanced-elimination & Antidotes chapter.
Ferrous fumarate ≈ 33% elemental iron; ferrous sulfate ≈ 20%; ferrous gluconate ≈ 12%. So a 300 mg fumarate tablet delivers ~99 mg of elemental iron, whereas a 300 mg gluconate tablet delivers only ~36 mg. For a 12 kg toddler, an ingestion crossing roughly 40–60 mg/kg elemental iron — a few high-strength adult tablets — is enough to threaten the shock/acidosis stage. Always convert to elemental iron and to mg/kg before judging risk; the tablet count alone is misleading.
- Activated charcoal does NOT bind iron — a classic decontamination exception.
- For large ingestions or visible tablets, use whole-bowel irrigation with polyethylene glycol.
- Time the serum iron level (peak ~4–6 h); track lactate and the metabolic acidosis, not appearance.
- Antidote: deferoxamine chelates free iron → ferrioxamine, renally excreted (urine may turn 'vin rosé').
- Reserve deferoxamine for severe toxicity: shock, acidosis, high iron level, or serious symptoms.
- Watch deferoxamine's hazards: hypotension with fast infusion; ARDS with prolonged use.
- Giving activated charcoal for iron — it does not adsorb metal ions and wastes time better spent on whole-bowel irrigation.
- Being reassured by the latent second stage and discharging the child — apparent recovery hides an advancing systemic acidosis.
- Judging risk by tablet weight or count instead of milligrams of elemental iron per kg — the salts differ several-fold.
A 3-year-old is brought in 5 hours after swallowing an unknown number of her mother's ferrous sulfate tablets. She vomited repeatedly earlier but now looks bright and playful. An abdominal X-ray shows several radio-opaque tablets in the stomach. What is the most appropriate next step?
- Iron is corrosive to the gut and, once absorbed, a free-radical cellular poison that saturates transferrin and drives a lactic acidosis and hepatic injury.
- Five stages: GI (0–6 h) → latent apparent-recovery (6–24 h, the trap) → shock & acidosis → hepatic failure (2–3 d) → late strictures (weeks).
- Assess with a timed serum iron level, a plain X-ray for radio-opaque tablets, and the metabolic (acidosis/lactate) trend; judge dose by elemental iron per kg.
- Charcoal fails; use whole-bowel irrigation, aggressive supportive care, and deferoxamine (chelates free iron → ferrioxamine) for severe toxicity.
- Goldfrank's Toxicologic Emergencies — Iron and deferoxamine.
- Rang & Dale's Pharmacology — Metals and chelating agents.
- Katzung Basic & Clinical Pharmacology — Heavy metal intoxication and chelators.
- British National Formulary (BNF) — Desferrioxamine (deferoxamine) and iron overdose.
- UpToDate / TOXBASE — Acute iron poisoning: clinical features and management.
- AACT/EAPCCT Position Statement — Whole-bowel irrigation and the role of activated charcoal.
