Humans lack effective means to excrete excess iron.
Long-term transfusions produce iron overload.
Each unit of red blood cell transfusion adds 200-250 mg of iron into the body’s iron burden..
Repeated transfusions are administered for sickle cell anemia, thalassemia major, myelodysplastic syndromes, myelofibrosis, aplastic anemia and other hematologic disorders.
In thalassemia major patients that receive transfusions in infancy, iron induced liver disease, endocrine disorders and cardiomyopathy frequently lead to death and adolescents.
With sickle cell anemia patients ultimately develop liver disease with cirrhosis as well as heart and pancreatic iron deposition.
Transfused red blood cells phagocytized by reticuloendothelial macrophages in the liver and bone marrow and spleen with the release of iron from heme.
Early in the course of chronic blood transfusions extra iron is stored within the reticuloendothelial macrophages, and when their capacity is exceeded iron is released into the plasma.
Iron released from the macrophages is bound to transferrin with an associated increase in plasma iron concentration and transferrin saturation.
When transferrin saturation increases, liver cells are recruited to serve as storage sites for the extra iron.
Eventually with continued transfusions macrophage and hepatocyte capacity to store iron is exceeded and it enters the plasma, exceeding the transport capacity of circulating transferrin as non-transferrin bound iron.
Iron overload can be treated with deferoxamine (Desferal) which can be given subcutaneously or intravenously for 8 to 12 hours each night to be effective.
Subcutaneous desferoxamine improves life expectancy of those who could adhere to infusions over 12 hours it for at least five days each week.
Other oral iron chelators deferasirox (Exjade) and Deferiprone (Ferripox) are available for patients as well.
With deferiprone up to 100 mg/day the iron excretion can go up to 0.6 mg per kilogram of body weight per day as compared to 0.3 to 0.5 mg per kilogram per day from blood transfusions in patients with thalassemia major.
MRI imaging of the liver allows quantification of tissue iron and permits the tailoring of chelation therapy based in organ specificI iron loading.
Thalassemia major, an inherited failure to synthesize the beta-globulin chain of hemoglobin, is the most common disease resulting in transfusion dependency worldwide.
Regular transfusions or administed in transfusion dependent patients to achieve a target level of 9 to 10. 5 g.
Transfusion dependent patients or monitored for overload with the use of serum ferritin measurements and hepatic and myocardial MRI and iron chelation is administered shortly after transfusion of ten red cell units or when the serum ferritin level is 1000 nanograms per milliliter or higher.
Three iron chelators, which can be used alone or in combination, or currently available for managing iron overload.
Subcutaneous desferoxamine, and the oral agents deferiprone, and deferasitox.
Desferoxamine and deferasitox are approved of patients older than 2 years of age, whereas deferipone is approved for second line therapy in patients older than six years of age.
All chelators can reduce systemic, hepatic, and myocardial iron in overload situation as mono therapies or in combination.
The choice of iron key later is based on guidelines, clinical judgment and patients preferences.
Continuous peripheral deep Roximine is the first choice for patients will already have cardiac dysfunction.