Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions

Article Abstract:

Thalassemia major is a severe hereditary anemia which affects children. It most frequently occurs within populations bordering the Mediterranean and in Southeast Asia; symptoms include severe anemia, fatigue, and cardiovascular complications. An excess of iron from frequent transfusions often accumulates in the blood of these patients. This condition of iron overload has been treated with deferoxamine, a drug that binds with the iron and allows it to be excreted. Recently, intravenous administration of deferoxamine has been used to treat thalassemia patients. Previously, deferoxamine had been administered by intramuscular injection or subcutaneous infusion. The effect of intravenous deferoxamine infusions was assessed in eight patients with thalassemia major who regularly received blood transfusions. Within nine days after starting the deferoxamine infusions, half of the patients developed complications of the lungs ranging from moderate to life-threatening severity. These pulmonary syndromes involved tachypnea (rapid breathing) and hypoxemia, or inadequate blood oxygen level. Abnormalities were also observed when pulmonary function tests, chest X-rays, and lung biopsies were performed. Inflammation of the lungs was evident and lymphocytes, eosinophils, and mast cells (immune system cells) were found in fluid samples, which signaled the body's reaction to disease, but no infectious agent was isolated. The correlation between administration of intravenous deferoxamine and pulmonary distress strongly suggested that the patients' lung complications were caused by the drug. Based on these findings, the researchers have recommended that patients be carefully monitored for pulmonary function during intravenous deferoxamine infusions. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Causes of, Lung diseases

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Toxic effects associated with the administration of deferoxamine in the premature baboon with hyaline membrane disease

Article Abstract:

When babies are born prematurely, damage to the lungs is believed to occur because of oxygen injury; an example is hyaline membrane disease, which affects the immature lungs of premature infants. The damage is believed to occur on a cellular level through the formation of toxic oxygen-containing molecules. However, this hypothesis has largely been based on tissue culture experiments and little information is available to show the linkage between oxygen level and damage in living animals. An experiment was designed using 12 baboons delivered prematurely by caesarian section. The ages of the animals were obtained from observing the day of mating, and the pregnancies were further confirmed by the use of ultrasound imaging. Each animal was assigned either to a group treated with deferoxamine or to a control group not receiving this drug. Deferoxamine is a compound that is able to reduce the chemical intermediates which are possibly responsible for the damage caused by high oxygen to the newborn. Each animal was placed on a ventilator with 100 percent oxygen for 6 days. Five of the seven untreated animals survived the experimental period and were then killed to provide tissues for examination. One of the animals treated with deferoxamine died after injection. As a result the other experimental animals received a decreased dose level. Four of the 5 treated baboons died during the experimental period. The experiment shows no protective effect of deferoxamine treatment against the development of lung lesions in premature baboons, and demonstrates a previously unreported toxicity to the drug. (Consumer Summary produced by Reliance Medical Information, Inc.)

Models, Active oxygen, Hyaline membrane disease

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Acute changes in renal function associated with deferoxamine therapy

Article Abstract:

Deferoxamine is a drug that rids the body of excess iron by binding the metal to another chemical; treatment with this drug is known as chelation therapy. Excess iron in the body can be produced by accidental swallowing of iron pills or by iron overload from multiple transfusions to treat blood diseases such as thalassemia. Patients with thalassemia have nightly infusions of deferoxamine to control iron overload. Although deferoxamine therapy is thought to be safe, some patients have encountered some adverse effects, such as hearing and vision loss and kidney damage. A study of three patients, two with thalassemia and one with iron tablet overdose, who were each receiving deferoxamine therapy, revealed that the drug increased the level of creatinine, a by-product of metabolism, by two to eight times. When the drug was discontinued, the clearance of creatinine resolved. The two patients with thalassemia had an increase in sodium, potassium, chloride and phosphate in the urine, which caused them to lose a large amount of fluid. Although each patient's experiences were different, it is thought that deferoxamine played a role in causing kidney failure. The toxic effects of deferoxamine on the kidneys should be considered when caring for patients undergoing chelation therapy. Increased fluids and constant monitoring of kidney functioning are suggested. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Chelation therapy, Exchange transfusion, Whole blood, Whole blood exchange transfusion

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