Iron overload blood transfusion

Since there is no major mechanism for excretion of iron except by cell desquamation and occult blood loss, iron overload is always a possibility when iron therapy is prescribed. Iron overload may also be caused by chronic blood transfusions. Two other conditions may be encountered haemachromatosis and iron poisoning. 

Hereditary hemochromatosis is an autosomal recessive disease of increased intestinal iron absorption and deposition in hepatic, cardiac, and pancreatic tissue. Hepatic iron overload results in the development of fibrosis, hepatic scarring, cirrhosis, and hepatocellular carcinoma. Hemochromatosis can also be caused by repeated blood transfusions, but this mechanism rarely leads to cirrhosis. 

A second form of storage iron is haemosiderin (Weir et al., 1984). This is deposited in humans as a response to the condition of iron overload. Haemosiderin forms as insoluble granules with electron dense cores surrounded by a protein shell. It exists in two forms primary haemosiderin is the result of iron overload due to excessive adsorption of iron in the gut, whereas the secondary form is caused by the numerous blood transfusions which are used to treat thallassaemia (a form of anaemia). Electron diffraction indicated that the iron core in primary haemosiderin is a 3-line ferrihydrite with magnetic hyperfine splitting only below 4 K and, in the secondary form, consists of poorly ordered goethite. As goethite is less soluble in ammonium oxalate buffer solution (pH 3) it has a lower intrinsic toxicity (Mann et al., 1988). 

Chronic iron overload 0.5 to 1 g IM daily. In addition 2 g IV infusion given separately with each unit of blood transfused. 

Deferasirox dispersible tablet For chronic iron overload due to blood transfusion... 

Deferasirox is a tridentate chelator with a high affinity for iron and low affinity for other metals, eg, zinc and copper. It is orally active and well absorbed. In the circulation, it binds iron, and the complex is excreted in the bile. Deferasirox was recently approved for the oral treatment of iron overload caused by blood transfusions, a problem in the treatment of thalassemia and myelodysplastic syndrome. 

Hoffbrand AY Al-Refaie F Davis B, et al. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood I 998 91 295-300. 

Under normal circumstances, transferrin is one-fourth to one-third saturated with iron. The level of saturation may decrease in systemic infection or cancer and in iron deficiency anemia, the most common nutritional deficiency in the United States. In individuals with iron deficiency anemia, transferrin levels are increased. The level of saturation with iron increases in iron overload syndromes such as hereditary hemochromatosis or as a result of repeated blood transfusions, as is the case in thalassemia patients. Determinations of total plasma iron (TI) and plasma total iron binding capacity (TIBC) are routinely performed in the clinical biochemistry laboratory. The TIBC value reflects transferrin levels in plasma the amount of iron that can be bound by transferrin is equal to TIBC x 0.7. Total plasma iron levels in iron deficiency anemia become abnormal before hemoglobin levels show any change. 

Patients with sickle cell disease often require blood transfusions. Most abnormalities of liver function in sickle cell patients result from infections transmitted by blood or as a result of iron overload from blood transfusion. Haemolysis due to sickle cell disease may result in increases in bilirubin. Patients may present with severe pain in the right... 

Conventional treatments for hemochromatosis and for nutritional iron overload include reduction of dietary iron and periodic removal of blood (phlebotomy) until iron stores are reduced. In transfusion siderosis, it is necessary to eliminate iron via the urine by the intravenous infusion of highly specific chelating agents such as desferral (see Iron Transport Siderophores). This process is painful, laborious, and costly. The development of new orally effective iron chelators is expected. 

Symptoms and signs of iron overload in transfusion-dependent anemias occur after a total transfusion burden of about 100-150 units of blood (49). 

Iron-overload disease, or hemochromatosis, may occur as a consequence of an, as yet, undefined genetic defect, or as a secondary effect of another medical disorder, such as thalassemia. In the former condition, primary hemochromatosis, iron accumulates in various tissues because of a lack of control of iron absorption from the gut. In the latter, or secondary hemochromatosis, the accumulation of iron results from the breakdown of red blood cells and the consequent need for frequent blood transfusions, which lead to an increase in the levels of tissue iron. In both cases the predominant store for iron is hemosiderin (147). 

Patients with inherited or acquired anemias that require regular blood transfusions frequently have symptoms or laboratory evidence of iron overload. Deferoxamine given subcutaneously at 40 mg kg over 8-12 h has been the standard of therapy for these patients. Patients receiving higher doses (e.g., 125 mg kg demonstrated ocular toxicity of blurriness, loss of night vision, and optic neuropathy. Auditory toxicity has been noted as well. Up to 25% of patients on chronic deferoxamine have some impairment of high-frequency hearing. 

In some adults, iron overload can be the result of a genetic defect (idiopathic hemochromatosis) that causes malfunction of the normal homeostasis mechanism and, in turn, excessive absorption of iron. Iron overload can also be caused by too many blood transfusions, which results in too much iron in the various iron-containing organs. 

Indications Chronic iron overload due to blood transfusions Category Chelator, iron Half-life 8-16 hours... 

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