Secondary Iron Overload

How to Cite This Chapter: Agarwal A, Verhovsek M, Mach T. Secondary Iron Overload. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed September 25, 2022.
Last Updated: July 21, 2019
Last Reviewed: July 21, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Secondary iron overload encompasses the following etiologies:

1) Iron-loading anemias, including thalassemias, sickle cell disease, sideroblastic anemias, chronic hemolytic anemia, pyruvate kinase deficiency, dehydrated hereditary stomatocytosis.

2) Iron overload secondary to excessive intake (iatrogenic or transfusional): Chronic or frequent red blood cell (RBC) transfusions, inappropriate iron therapy (oral or IV).

3) Miscellaneous causes: Porphyria cutanea tarda, aceruloplasminemia, congenital atransferrinemia.

Clinical Features and Natural HistoryTop

Clinical features are similar to primary hemochromatosis.

Natural history is specific to the etiology of secondary iron overload and will not be explored in detail in this chapter.


As in primary hemochromatosis, serum ferritin is a useful screening test for iron overload. Magnetic resonance imaging (MRI) or liver biopsy (or both) are used to quantify hepatic iron concentration and guide therapy.

1. Blood tests: A general cutoff of ferritin >1000 microg/L can be applied for most cases of secondary iron overload, although it is increasingly recognized that in non–transfusion-dependent thalassemias (NTDTs) (eg, beta thalassemia intermedia and hemoglobin H disease) and other inherited hemolytic anemias iron overload can be present at ferritin levels ≥300 microg/L. Transferrin saturation is useful in confirming the presence of iron overload.

2. MRI: MRI R2 or R2* scans of the liver with validated image analysis provide noninvasive quantification of hepatic iron overload and are considered the standard of care in the assessment of iron overload in transfusion-dependent thalassemia, NTDT, and sickle cell disease. Selected patients may also require specialized MRI iron assessment of other organs (eg, the heart, pancreas, or pituitary).

3. Liver biopsy for hepatic iron concentration and histopathologic iron staining can be used to directly assess hepatic iron concentration while also examining the liver tissue for findings of fibrosis. If noninvasive MRI assessment is available, liver biopsy is less likely to be used because of the procedural risks and potential for inaccurate estimation of the total hepatic iron content when hepatic iron distribution is patchy.


Treatment should be focused on the underlying condition whenever possible.

Phlebotomy is useful for certain types of secondary iron overload. It is clearly indicated in porphyria cutanea tarda (reduction in skin manifestations), and small volume phlebotomy (“miniphlebotomy”) can often be safely and successfully used in patients with NTDTs with normal or near-normal baseline hemoglobin.

In patients who are ineligible for phlebotomy, including all who are transfusion-dependent, pharmacologic iron chelation strategies are used. Deferoxamine is a parenteral therapy that can be administered via a continuous subcutaneous or IV infusion 8 to 24 hours per day at a total daily dose of 20 to 60 mg/kg/d. Options of oral iron chelation include deferasirox 10 to 40 mg/kg/d or deferiprone 75 to 100 mg/kg/d (total daily dose divided into tid dosing). Selection of iron chelation regimens depends on coexisting comorbidities, medication availability, and patient preference for administration route and frequency, as well as organs affected by iron overload and severity of iron loading. In our experience, iron chelation is typically managed by specialized medical teams.


Patients with iron overload require ferritin monitoring at regular intervals (eg, every 1-4 months). Selected patients, as outlined (see Diagnosis, above), also benefit from MRI monitoring of hepatic iron concentrations. Specialized liver MRI will often be completed annually to monitor therapeutic effects.


Previously, when the availability of iron chelation agents was limited, complications of organ iron overload were one of the main causes of early mortality in patients with transfusion-dependent thalassemia. With the advent and growing availability of a variety of iron chelation drugs, it is expected that patients with these conditions will now have dramatically improved life expectancy.

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