Management of transfusional iron overload – differential properties and efficacy of iron chelating agents

Figures & data

Table 1 Clinical implication of ferritin levels and liver iron concentration

Liver iron concentration (mg/g dw)	Ferritin level^a(ng/mL)	Clinical implications
<2	<500	Low iron stores; consider decreasing or holding chelation temporarily^b
2–7	500–1499	Ideal range; continue current chelation
>7–15	1500–2500	Increased iron stores; increase chelator dose^c and/or change chelator if ferritin and/or liver iron trend is not improving
>15	>2500	Elevated iron stores associated with increased risk of complications and death; increase chelator dose^c and/or change chelator; consider combination chelation therapy

Notes:

a Ferritin should be obtained when patient is clinically well and vitamin C replete;

b chelation should not be held if cardiac iron loading is present (cardiac T2* <20 ms) ;

c chelator dose should not exceed approved range (see Table 3).

Table 2 Clinical implications of cardiac iron assessment by T2* magnetic resonance imaging

Cardiac T2* (ms)	Clinical implication
≥20	No significant cardiac iron loading; continue current chelation
10 to <20	Mild to moderate cardiac iron loading with increased risk of cardiac complications; consider intensification of chelation such as increased dose^a and/or continuous infusion (for deferoxamine); combination therapy with deferiprone and deferoxamine if available
<10	Severe cardiac iron loading with high risk of cardiac complications; intensify chelation such as increased dose^a and/or continuous infusion (for deferoxamine); combination therapy with deferiprone and deferoxamine if available

Note:

a Chelator dose should not exceed approved range (see Table 3).

Table 3 Properties of iron chelators

Property	Deferoxamine	Deferasirox	Deferiprone
Stoichiometry (chelator: iron)	Hexadentate (1:1)	Tridentate (2:1)	Bidentate (3:1)
Usual dose	25–60 mg/kg/day over 8–24 hours	20–40 mg/kg/day once daily	75–100 mg/kg/day in three divided doses
Route of administration	Subcutaneous, intravenous	Orally dispersible tablet	Oral tablet or suspension
Half-life	20–30 minutes	7–16 hours	1.5–2.5 hours
Excretion	Urinary, fecal	Fecal	Urinary
Ability to remove liver iron	+++	+++	++^Table Footnote*
Ability to remove cardiac iron	++^#	++^Table Footnote**	+++
Typical adverse events	Local reactions	Gastrointestinal	Gastrointestinal
	Sensorineural hearing loss	Rash	Neutropenia/Agranulocytosis
	Ophthalmic changes	Rise in creatinine	Arthralgia
	Allergic reactions	Proteinuria	Elevated hepatic enzymes
	Bone abnormalities	Elevated hepatic enzymes
	Increased risk of Yersinia and Klebsiella infections	Gastrointestinal bleeding (rare)
		Fulminant hepatic failure (rare)
	Pulmonary at high doses	Renal insufficiency (rare)
	Neurological at high doses
Availability	Licensed	Licensed	Licensed in Europe and Asia as second-line agent; not licensed in North America

Notes:

* Reports of insufficient liver iron removal in some patients at doses of 75 mg/kg/day, but higher dosing, especially for subjects with high transfusional iron burden may be more effective;

# with continuous infusion;

** data are limited regarding efficacy with very low cardiac T2* and in heart failure; cardiac iron removal also may be less effective in patients with high liver iron concentration.