Iron chelation therapy

What it is

Chelation is how iron overload is removed, and the overload comes in two forms: the chronic transfusional overload of beta thalassemia major, and acute overload after an overdose. Three chelators are used: deferoxamine, deferasirox and deferiprone. They differ in route, in how often they are given, in the iron they target, and in what has to be monitored while they are given.

How it is treated

• Deferoxamine, DFO, is parenteral, an IV or SubQ infusion given 5-7 days a week over an 8-12h infusion. Its main use is acute iron overload and transfusional hemosiderosis, and the iron it targets is liver, with some cardiac. Adverse effects are ototoxicity, retinal damage and growth retardation, so monitoring is by audiometry, vision and ferritin. It is the gold standard in acute overload.
• Deferasirox, DFX, is oral, a tablet or dispersible form, once daily, for chronic transfusional iron overload; the iron it targets is liver, with some cardiac. Adverse effects are GI upset, liver enzymes and renal issues, so monitoring is by LFTs, renal function and ferritin. Being oral and once daily it is the most convenient of the three.
• Deferiprone, DFP, is oral, a tablet or syrup, three times daily. It is often used when DFO or DFX is not tolerated, or for cardiac iron, where it is very effective and is the best of the three for cardiac iron removal. Adverse effects are agranulocytosis, neutropenia and arthropathy, so a weekly CBC for neutropenia is needed, with ferritin.

Acute iron overdose is treated apart, and deferoxamine IV is the chelator in it. A dose ingested above 20mg/kg of elemental iron, or an unknown amount, is what leads into it, and from there the patient takes one of three paths. An asymptomatic patient: consider WBI, obtain a KUB x-ray and obtain a 4 hours post ingestion serum iron level, and a patient still asymptomatic at 6 hrs postingestion is discharged. Only GI symptoms: volume resuscitation, assess acid-base status, obtain a KUB x-ray, consider WBI and obtain a 4 hours post ingestion serum iron level. Systemic toxicity: stabilize the patient, volume resuscitation, assess acid-base status, obtain a serum iron level and a KUB x-ray, and consider WBI. Upper endoscopy, or gastrotomy and surgical removal of iron tablets, is considered with life-threatening toxicity where iron persists in the GI tract despite WBI. Deferoxamine IV is started when the serum iron level is above 500 microg/dL, or when there is metabolic acidosis, or when symptoms persist or develop. The usual starting dose is 90 mg/Kg given IV at a rate of 10 - 15 mg/kg/hr in adults and children over 3 years old, and 15 mg/kg/hr is not exceeded except in extreme cases. Urine color is not a guide to therapy; iron levels are followed closely instead. Chelation should proceed until the serum iron level is under 100 microg/dL, or until the patient is doing clinically better.