Transfusion-induced Iron Overload Research Articles

Bone disease in β-thalassaemia

Regular blood transfusion and iron-chelation therapy have substantially extended the life-expectancy of patients with β-thalassaemia major. Unfortunately, the consequences of transfusion-induced iron overload and blood-transmitted hepatitis remain major causes of morbidity and mortality. Bone disease is an another, increasingly recognised, cause of serious morbidity in thalassaemic patients. Patients commonly present with bone deformities, scoliosis, chronic bone pain, osteoporosis, fractures, growth failure, or nerve compression. The case reported in today's Lancet by Enrico Parano and colleagues highlights the severe bone reactions that can occur in thalassaemia intermedia. Extraordinary intrathecal bone reaction in β-thalassaemia intermediaWe report on a patient with thalassaemia which was refractory to blood transfusions. The clinical picture was striking, and highlights the potential severity of intrathecal bone reactions after chronic intractable haemolytic anaemia. Full-Text PDF

Prolonged Clinical Use of a Heme Oxygenase Inhibitor: Hematological Evidence for an Inducible but Reversible Iron-Deficiency State

The heme oxygenase inhibitor tin (Sn4+)-mesoporphyrin, administered to two 17-year-old Crigler-Najjar type I patients during a 400-day study to lower plasma bilirubin levels, also produced changes, beginning approximately 50 days after initiation of treatment, in hematological and iron metabolism indices consistent with the development of iron deficiency anemia. These indices were responsive to iron supplementation and reverted to normal after termination of inhibitor treatment. Tin-mesoporphyrin enhances biliary heme excretion and inhibits intestinal heme oxygenase when administered orally or parenterally; the changes in blood indices could thus reflect, in part, blockade of heme catabolism and therefore of uptake of heme-derived iron, by intestinal epithelium. This action of the inhibitor suggests that such agents may facilitate studies involving aberrant metabolism of heme-derived iron in humans and that they merit further investigation with respect to their potential value in enhancing iron disposal in certain disorders such as those related, for example, to transfusion-induced iron overload states.

166 THE RELATIONSHIP BETWEEN DISTURBED LIVER FUNCTION, IRON AND MARKERS OF HEPATITIS B UIRUS INFECTION IN BRITISH CHILDREN WITH BETA THALASSAEPIIA

Although chronic liver dysfunction in β Thalassaemia major has been associated with transfusion induced iron overload. Chronic Hepatitis B virus (HBV) infection has also recently been implicated. We, therefore, studied 16 children (8 male, 8 female) aged 1-14 years, to assess the influence of iron overload measured by serum ferritin and the volume of transfused blood, and the presence of markers of HBV infection (HBs Ag, HBc Ab, HBs Ab) on liver dysfunction. Thirteen children had elevated serum transaminases; 6 of these had received > 10D units of blood and had had serum ferritin levels of > 6,000mcg/L. All 16 received chelation therapy with a fall in serum ferritin levels from a maximum of 1280-13, 900mcg/L to a minimum of 370-5, 450mcg/L. Concommitant improvement in liver function occured in 10. Although 11 patients had visited HBV endemic areas and 6 had been transfused there, only 2 developed markers of HBV infection. Both had clinical, biochemical and serological evidence of acute HBV infection; they had abnormal liver function prior to the HBV infection, and transaminases returned to these levels after the acute HBV infection. Thus in children, iron overload rather than HBV infection is the major cause of chronic liver dysfunction. However, active immunisation against HBV is necessary to protect these children who commonly receive transfusion whilst in endemic areas.

OCULAR TOXICITY OF HIGH-DOSE INTRAVENOUS DESFERRIOXAMINE

Desferrioxamine was given intravenously, at higher doses than previously reported, to counter the effects of transfusion-induced iron overload in four patients with beta thalassaemia major. In two of them retinal abnormalities developed, presenting with night blindness and field defects, which improved on withdrawal of the drug.

Reassessment of the use of desferrioxamine B in iron overload.

Treatment of transfusion-induced iron overload by daily intramuscular injection of the chelator desferrioxamine has not produced impressive urinary iron excretion. We attempted to augment net iron excretion by altering both the route and quantity of chelator administered. Two ascorbic acid-replete patients excreted a mean of 14.5 mg of iron per 24 hours after a single intramuscular injection of 750 mg of desferrioxamine. Excretion increased to a mean of 44.9 mg when this dose was delivered by a continuous 24-hour intravenous infusion. When the intravenous dose of chelator was increased incrementally to as high as 16,000 mg per 24 hours, iron excretion increased up to 180 mg per day. At these high-dose levels, efficiency of binding of iron to chelator was compromised. Constant exposure of the labile iron pool to a chelating agent markedly enhances net iron excretion in splenectomized transfusion-dependent patients.

The inhibitory effect of vitamin E on desferrioxamine-induced iron excretion in rats.

The influence of vitamin E on the mobilization and excretion of storage iron induced by DF was studied in normal and iron-overloaded rats. Vitamin E administration in pharmacologic doses resulted in complete inhibition of the effect of DF on storage iron in iron-overloaded rats while no such effect could be demonstrated in rats with normal iron stores. The mechanism of the observed inhibition of DF action by vitamin E is at present unknown. Nevertheless this drug interaction has to be considered in view of ongoing therapeutic trials where both antioxidants and iron chelating drugs are administered simultaneously to thalassemic patients with transfusion induced iron overload.