Iron Overload: Consequences, Assessment, and Monitoring

In patients suffering from transfusion-dependent anemia, excess iron secondary to regular transfusions cannot be physiologically excreted. This leads to a state of chronic iron overload with iron accumulating in the liver, heart, and endocrine organs, and ultimately results in significant morbidity and mortality. Historically, iron overload was assessed through measurement of serum ferritin or direct determination of liver iron concentration (LIC) by means of biopsy. Although both correlate well with iron overload severity, several limitations pertinent to both are of concern. This has led to the identification of novel noninvasive iron assessment measures, namely magnetic resonance imaging (MRI) R2 and T2*. Moreover, investigations of other potential indices like nontransferrin-bound iron (NTBI) and labile plasma iron (LPI) are yielding promising results. Optimal iron overload assessment and monitoring is a key element in the development of improved strategies of iron chelation therapy that can be tailored to meet the patient's specific needs.

[1]  C. McLaren,et al.  Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major , 1993, American journal of hematology.

[2]  C. McLaren,et al.  Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. , 1994, The New England journal of medicine.

[3]  S. Shalitin,et al.  Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients , 2005, European journal of haematology.

[4]  T. Ganz,et al.  Liver iron concentrations and urinary hepcidin in beta-thalassemia. , 2007, Haematologica.

[5]  J. Wood.  Cardiac iron across different transfusion-dependent diseases. , 2008, Blood reviews.

[6]  Z. Cabantchik,et al.  LPI-labile plasma iron in iron overload. , 2005, Best practice & research. Clinical haematology.

[7]  N. Olivieri,et al.  Progression of iron overload in sickle cell disease. , 2001, Seminars in hematology.

[8]  A. Hoffbrand,et al.  Hepatic iron concentration combined with long‐term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major , 2000, British journal of haematology.

[9]  A. Cnaan,et al.  Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. , 2004, Haematologica.

[10]  D. Farmakis,et al.  Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. , 2007, Haematologica.

[11]  J. Villeneuve,et al.  Variability in hepatic iron concentration measurement from needle-biopsy specimens. , 1996, Journal of hepatology.

[12]  C. McLaren,et al.  Hepatic iron concentration and total body iron stores in thalassemia major. , 2000, The New England journal of medicine.

[13]  A. Piga,et al.  Results of long-term iron-chelating therapy. , 1996, Acta haematologica.

[14]  A. Taher.  Iron overload in thalassemia and sickle cell disease. , 2005, Seminars in hematology.

[15]  E. Neufeld,et al.  Urinary hepcidin in congenital chronic anemias , 2007, Pediatric blood & cancer.

[16]  E. Vichinsky,et al.  Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients , 2007, Pediatric blood & cancer.

[17]  Roger Williams,et al.  Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. , 2000 .

[18]  F. Jensen,et al.  Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias. , 2003, Blood.

[19]  O. Simonetti,et al.  Design and Methods Study Population , 2022 .

[20]  A. Aessopos,et al.  Thalassemia intermedia today: should patients regularly receive transfusions? , 2007, Transfusion.

[21]  M. Cappellini,et al.  Survival and Disease Complications in Thalassemia Major , 1998, Annals of the New York Academy of Sciences.

[22]  E. Rachmilewitz,et al.  Non‐Specific Serum Iron in Thalassaemia: an Abnormal Serum Iron Fraction of Potential Toxicity , 1978, British journal of haematology.

[23]  M. Cappellini,et al.  Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia , 2008, Haematologica.

[24]  G. Link,et al.  Pathophysiology of Iron Overload a , 1998, Annals of the New York Academy of Sciences.

[25]  D. Pennell,et al.  Normalized left ventricular volumes and function in thalassemia major patients with normal myocardial iron , 2007, Journal of magnetic resonance imaging : JMRI.

[26]  G. Anderson.  Mechanisms of iron loading and toxicity , 2007, American journal of hematology.

[27]  H. Eiskjaer,et al.  Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool. , 2003, Blood.

[28]  S. Marelli,et al.  Non-transferrin-bound iron, iron-related oxidative stress and lipid peroxidation in beta-thalassemia intermedia. , 2000, Transfusion science.

[29]  P. Jarritt,et al.  Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major. , 2004, Blood.

[30]  M. Cappellini,et al.  Oxidative status and malondialdehyde in β‐thalassaemia patients , 2002 .

[31]  C. Tiribelli,et al.  Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases. , 2008, Liver.

[32]  W. Breuer,et al.  The importance of non-transferrin bound iron in disorders of iron metabolism. , 2000, Transfusion science.

[33]  D N Firmin,et al.  Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. , 2001, European heart journal.

[34]  G. Lucarelli,et al.  Needle liver biopsy in thalassaemia: analyses of diagnostic accuracy and safety in 1184 consecutive biopsies , 1995, British journal of haematology.

[35]  Marvin D Nelson,et al.  Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease. , 2004, Blood.

[36]  I. Papassotiriou,et al.  Magnetic resonance imaging in the evaluation of iron overload in patients with beta thalassaemia and sickle cell disease , 2004, British journal of haematology.

[37]  S. Fucharoen,et al.  Liver injury due to iron overload in thalassemia: histopathologic and ultrastructural studies , 1996, Biometals.

[38]  T. S. St. Pierre,et al.  Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. , 2005, Blood.

[39]  J. H. MacMillan,et al.  Survival in Medically Treated Patients with Homozygous β-Thalassemia , 1994 .

[40]  M. Cappellini,et al.  Thalassemia intermedia: revisited. , 2006, Blood cells, molecules & diseases.