Transfusional Iron Overload
Patients who require repeated blood transfusions inevitably must contend with the cumulative toxicity of chronic iron overload (1). Each unit of red blood cells contains about 200 mg of heme iron — more than 100 times the iron typically absorbed from the diet each day (2).
Survival benefit in severe chronic anemia
For patients with severe chronic anemia, regular blood transfusions may represent life-saving therapy. However, regular transfusions can themselves represent a significant morbidity and mortality risk, if appropriate iron reduction therapy is not provided (1).
Survival benefit in severe chronic anemia
Patients with thalassemia major experienced substantial increases in life expectancy when given regular, as opposed to irregular, blood transfusions.
Adapted with permission from Modell, Berdoukas (3).
Transfusion-dependent anemias
Examples of transfusion-dependent anemias include:
- Aplastic anemia
- Diamond-Blackfan anemia (red blood cell aplasia)
- Dyserythropoietic anemias
- Fanconi anemia (hypoplastic anemia)
- Myelodysplastic syndromes
- Sickle cell anemia
- Thalassemia major
Iron overload and transfusion burden
Regularly transfused patients can accumulate excess iron at up to 0.5 mg/kg/day (4). After receiving 20 lifetime units of packed red blood cells, patients can become iron overloaded. No matter how many years pass between transfusions, the dangers are the same, because the body has no way actively excrete excess iron. Iron overload is proportional to transfusion burden (2,5).
Iron overload is proportional to transfusion burden (1)Iron overload is proportional to transfusion burden
Impact of transfusional iron overload on survival
Iron overload has been shown to be an independent mortality risk factor in sickle cell disease, myelodysplastic syndromes, and thalassemia major.
Iron overload is associated with increased mortality in SCDIron overload is associated with increased mortality in SCD
Mortality over a 12-year period in patients with and without iron overload. Adapted with permission from Ballas, et al (6).
More about transfusional iron overload in SCD
Transfusion burden in myelodysplastic syndromes (MDS)
Transfusion burden in myelodysplastic syndromes (MDS)
Cox proportional hazard regression analysis of survival based on transfusion requirement in 426 patients with MDS.
U PRC = units of packed red cells.
Adapted with permission from Malcovati, et al (7).
More about transfusional iron overload in MDS
Liver iron concentration and survival in thalassemia major
Liver iron concentration and survival in thalassemia major
In a study of patients with thalassemia major, high liver iron concentrations (LIC) were significantly associated with premature death (iii), compared to low (i) or moderate (ii) LICs. High LIC was defined as > mg Fe/g of liver dry weight; moderate was 7-15 mg/g; low was <7 mg/g.
Adapted with permission from Telfer, et al (8).
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Iron and Hepatic Damage
The development of liver fibrosis
directly correlates
to liver iron concentrations and serum ferritin levels.
References
- (1) Andrews NC, Disorders of iron metabolism. N Engl J Med. 1999;341(26):1986-95.
- (2) Porter JB, Practical management of iron overload. Br J Haematol. 2001;115(2):239-52.
- (3) Modell B, Berdoukas V, The clinical approach to thalassemia. 1984, New York: Grune and Stratton. p. 171.
- (4) Gabutti V, Piga A, Results of long-term iron-chelating therapy. Acta Haematol. 1996; 95(1):26-36.
- (5) National Institutes of Health, National Heart, Lung, and Blood Institute: The Management of Sickle Cell Disease. 2002, Bethesda, MD: NIH.
- (6) Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001;38(1 Suppl 1):30-6.
- (7) Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome [editorial]. Haematologica. 2006;91:1588-90
- (8) Telfer PT, Prestcott E, Holden S, et al., Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol 2000; 110(4):971-7.