Iron toxicity and iron chelation therapy
For patients requiring regular blood transfusions, iron toxicity is a serious risk. Iron toxicity occurs when the capacity of the patient's transferrin is no longer sufficient to bind with and regulate circulating iron thereby maintaining proper iron levels. In order to avoid the onset of iron toxicity in transfusion patients, iron chelation therapy is routinely implemented. Iron chelation is an important therapy for such patients where iron overload if left untreated can have serious consequences. Indeed in patients with thalassaemia major, the availability of iron chelation therapy led to one of the most marked improvements in morbidity and mortality associated with a genetic disease. In a landmark study investigating whether deferoxamine (Desferal®) prevented complications of iron toxicity and transfusional iron overload, survival to at least 25 years of age in poorly chelated β-thalassemia major patients was just one-third that of patients whose iron levels were well managed by deferoxamine [1].
Effective iron chelation therapy reduces iron toxicity and extends life expectancy in thalassaemia major
Adapted with permission [1].
When the capacity of transferrin to bind iron is exceeded, non-transferrin-bound iron (NTBI) develops in the plasma and iron toxicity sets in. The uptake of NTBI is non-specific, uncontrolled and often occurs in susceptible tissues. Within the cells, iron toxicity occurs when pools of intracellular labile iron accumulate and mediate tissue damage via the formation of harmful reactive oxygen species (ROS) [2;3]. The major goal of iron chelation therapy is to bind NTBI and intracellular labile iron, thereby effectively eliminating toxic levels of iron. Due to the cumulative nature of iron loading, continuous (24-hour) control of NTBI levels is desirable for the avoidance of iron toxicity damage.
Assessing and managing iron toxicity and iron overload
Although a liver iron concentration (LIC) of <7 mg Fe/g dry weight (dw) has been proposed as a generally attainable target in treating iron overload and avoiding iron toxicity, optimal targets are lower (3.3-7.0 mg Fe/g dw) [4]. Only a small fraction of the total body iron is available for chelation at any given time, therefore it may take some time to attain normal tissue iron levels. However, with iron chelation therapy a reduction in morbidity and mortality is achievable within a relatively reasonable timeframe. For any given patient, reaching their target body iron levels depends to a large extent on their ability to comply with long-term iron chelation therapy, which itself is largely determined by the side effects, tolerability, perceived efficacy and convenience of the iron-chelating agent.
  References
(1) Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW: Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994; 331(9):567-573.
(2) Britton RS, Leicester KL, Bacon BR: Iron toxicity and chelation therapy. Int J Hematol 2002; 76(3):219-228.
(3) Hershko C, Link G, Cabantchik I: Pathophysiology of iron overload. Ann NY Acad Sci 1998; 850:191-201.
(4) Olivieri NF, Brittenham GM: Iron-chelating therapy and the treatment of thalassemia. Blood 1997; 89(3):739-761.
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