[Iron accumulation in the liver of patients with thalassemia major assessed with low field strength magnetic resonance: correlation with clinico-instrumental parameters]. / Accumulo di ferro nel fegato di pazienti con talassemia major valutato mediante risonanza magnetica con bassa intensità di campo: correlazione con i parametri clinico-strumentali.

Eight transfusion dependent patients (3 women and 5 men) with thalassemia major undergoing long-term treatment with Desferoxamine were submitted to MRI, with T2* GE sequences and low field strength. The ratio between liver mean signal intensity and skeletal muscle (L/M) and the ratio between the former and subcutaneous fat (L/F) were calculated in all patients. The results were compared with those of a control group of 7 healthy volunteers (7 men). L/M and L/F ratios were separately correlated with the following parameters: patient's age, transfusion history, serum ferritin, ferritin peak and its onset, transaminases (AST and ALT) and chelation index. The latter is a complex parameter allowing the actual assessment of iron content and of the real efficacy of chelation therapy. In all patients, both the L/M and the L/F ratios decreased significantly (L/M ratio: 0.67 +/- 0.45 vs. 1.2 +/- 0.21, p < 0.02; L/F ratio: 0.39 +/- 0.15 vs. 0.84 +/- 0.11, p < 0.001) relative to the control group. No significant correlation was found between the ratios and any hematochemical parameter, except for r = 0.77 (p < 0.04) between L/F ratio and the chelation index. Our study demonstrates that MRI may play a major role in the examination of thalassemic patients even at low field strength and with GE sequences, which yield good quality images with a relatively short acquisition time. Thus, MRI can be suggested for routine liver studies thanks to its high quality depiction of the liver and to its qualitative and semiquantitative yield. The good correlation between L/F ratio and the chelation index permits MR evaluation of the efficacy of different chelation treatments.

Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy.

Nineteen transfusion-dependent beta-thalassemia major patients were included in the study. Six of these patients underwent chelation therapy with desferrioxamine by subcutaneous infusion (50 mg/kg/12 hr) and 13 received intravenous infusion (50 mg/kg/6 hr or 100 mg/kg/24 hr). BUN, creatinine, creatinine clearance, beta 2-microglobulin, urinary beta 2-microglobulin and urinary growth hormone excretion were evaluated during desferrioxamine treatment. Thirteen out of nineteen patients presented tubular damage indicated by increased excretion of urinary beta 2-microglobulin. 85% (11 of 13) of these patients showed more serious tubular damage, as demonstrated by concurrent increased urinary growth hormone excretion. Moreover, a positive correlation between urinary growth hormone excretion and urinary beta 2-microglobulin was observed (P < 0.05).

Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis.

A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine.

Toxic effects of high-dose deferoxamine treatment in patients with iron overload: an electrophysiological study of cerebral and visual function.

BACKGROUND AND METHODS: It is well known that deferoxamine (DFO) treatment in thalassemia major can produce ocular toxicity. In one experience, Visual evoked potentials (VEPS) to pattern reversal were formed to be altered in 4 out of 10 patients under conventional treatment with DFO, before supplementary high-dose i.v. deferoxamine. In all 4 cases the alterations consisted of bilaterally delayed P100 latency, always obtained by stimulation with high spatial frequency (15' checks) and associated in three cases with low spatial frequency (55'). Computerized EEG (cEEG) studies showed a generalized increase of slowing activity. All patients underwent high-dose DFO treatment. RESULTS: At the control performed at the end of treatment in all 4 cases with previous VEP alterations, a further delay in P100 latency was observed bilaterally while two of the six patients, without previous involvement, showed delayed responses when using checks of 15'. The EEG slowing activity was not modified. Three weeks after terminating i.v. DFO therapy, the patients were still under subcutaneous treatment (50 mg/kg/day); a more evident VEP recovery towards the initial values was observed in those patients without initial alterations. No significant changes were found between electrophysiological parameters and serum ferritin levels. CONCLUSIONS: Our results indicate that high-dose DFO therapy in patients with iron overload induces reversible visual impairment without significant changes in brain electrical activity. The employment of VEP in intensive chelation programs in thalassemia major is discussed.