Steven R. Ellis, PhD Research Director

Before delving into the journal article itself, I thought I would provide a little background on how the body handles iron.  Iron, while essential for life, is also very toxic because of its propensity to form reactive oxygen species which can damage many cellular components.  The body regulates the amount of iron, carefully maintaining its levels between acceptable limits.  Somewhat surprisingly, once iron gets into the body, it stays; and is only loss through bleeding (the iron in hemoglobin) or by a small amount of cellular sloughing that occurs each day.  Thus, the main way that iron levels are maintained is by carefully controlling uptake into the body from the diet.  The amount of iron absorbed through the gut is just enough to offset the small amount normally lost each day, with most iron in the diet passing through the gut and not being absorbed into the body.  This careful system of regulation is subverted when a person is transfused, as the iron of hemoglobin in red blood cells is added directly into a person's circulation bypassing the normal system of regulation in the gut.  As stated earlier, iron once in the body, does not get efficiently eliminated, and so iron will begin to accumulate with each transfusion.  This excess iron is then stored in tissues like the liver, heart, and pancreas where it can eventually lead to organ damage and as such, the complications of iron overload.  Chelation therapy is used to treat or prevent iron overload.  During chelation therapy, small molecules bind  iron forming a complex which is then eliminated from the body in the urine and feces, thereby providing a means for reducing the body's iron load. 

Roggero and colleagues studied records from 31 transfusion dependent DBA patients in Italy dating from the year 2000.  The data collected included the number of transfusions, the volume of blood received, liver iron concentration, and other related parameters.  Despite the risks of iron overload, this study found that 54% of patients showed evidence of severe iron overload as defined by liver iron concentration.  Over half of this severe iron overload could be attributed to inappropriate prescription (how chelation therapy was delivered) and a smaller, but very substantial percentage, to poor compliance by the patient, both of which could potentially be remedied.  It should be noted, that these values were not for the US population which could differ.  However, since a similar study has not been performed on the US population, it is unclear where we stand in this regard. 

One of the more intriguing observations from the Italian study came from comparing iron overload in DBA patients with iron overload in thalassemia patients receiving similar amounts of iron.  The authors state that iron overload was significantly higher in their DBA population when compared to matched thalassemia patients.  There are many complexities associated with comparing iron overload between DBA and thalassemia patients, so the authors were unwilling at the time to conclude that there is an intrinsically higher propensity of DBA patients to develop iron overload.  If, however, these results are confirmed in other studies, it may suggest that there may be disease-specific differences in how the body manages excess iron. 

This study concludes that iron overload is a serious and relatively common occurrence in DBA patients.  I would suspect that this comes as no real surprise to anyone familiar with DBA.  And yet, the magnitude of the problem, at least in Italy, suggests a need for a similar study in the US, and if necessary, that appropriate actions be taken.  Finally, there has been tremendous progress in our understanding of the mechanisms through which the body regulates iron homeostasis.  Whether some of these mechanisms will be harnessed to create a potential alternative to chelation therapy remains to be seen.