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Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload.

BACKGROUND AND OBJECTIVE: Chelation therapy is often necessary for patients who undergo chronic transfusion therapy for myelodysplastic syndromes. In these patients, deferoxamine, the most widely used chelating agent, has been reported to be effective in reducing the iron burden and the transfusion requirement. Unfortunately, compliance with the drug, that is usually administered by slow subcutaneous infusion via a battery operated pump, is often poor, especially in elderly patients. DESIGN AND METHODS: To verify efficacy and tolerability of deferoxamine by subcutaneous bolus injection as compared to the conventional pump-driven slow infusion, eleven patients affected by oncohematologic diseases were given 2 g of deferoxamine diluted in 10 mL of distilled water over twelve hours by continuous infusion, or by bolus injection in two divided doses. RESULTS: Mean urinary excretion was comparable with the two methods, being 9,183 +/- 4,349 micrograms/48 h after two daily subcutaneous bolus injections and 8,291 +/- 3,970 micrograms/48 h with the slow infusion. The bolus injection was preferred by all eleven patients, who chose to continue chelation therapy by this method. INTERPRETATION AND CONCLUSIONS: The iron excretion induced by bolus injection is not statistically different from that induced by subcutaneous infusion. The side effects are acceptable. Subcutaneous bolus injection of deferoxamine is an acceptable alternative to slow, pump-driven infusion.

Adult↗

Prevalence of iron deficiency and iron overload in the adult Icelandic population.

The aim of this cross-sectional study was to estimate the prevalence of iron deficiency and overload in the adult population in Iceland, a developed Scandinavian country. The study population consisted of 4240 individuals aged 25-74 years randomly selected from the national roster. Basic hematological, S-iron, S-total iron binding capacity (TIBC), and S-ferritin measurements were obtained on 2588 individuals (61.0%). The results indicated unusually large iron stores in the adult Icelandic population and significantly larger iron stores in the rural compared to the urban population. Iron deficiency was rare except in urban premenopausal women, where 1 in 4 showed evidence of iron deficiency and 3.2% had iron deficiency anemia. Seven patients with hereditary hemochromatosis were identified from a subgroup of 1887 subjects, resulting in a prevalence of 0.37%. Two of the hereditary hemochromatosis patients had been gastrectomized. Measures to improve the iron balance in urban premenopausal women cannot therefore include increased iron fortification of food but must be more directed towards the target group.

Adult↗

Iron overload states.

Hereditary hemochromatosis is a common disorder of iron metabolism that increasingly is diagnosed and treated prior to the development of cirrhosis or diabetes. The discovery of a candidate gene for hereditary hemochromatosis undoubtedly will result in improved diagnosis of hereditary hemochromatosis and to a better understanding of certain aspects of iron absorption, hepatic iron uptake and release, and whole body iron metabolism. In turn, this enhanced understanding of iron biology can be applied to the observations seen in patients with other hepatic diseases such as chronic viral hepatitis.

Hemochromatosis↗

Ankylosing spondylitis: a chronic inflammatory disease with iron overload in granulocytes and platelets.

The cellular stores of iron in granulocytes and platelets isolated from 29 patients with ankylosing spondylitis were measured by the nuclear microprobe technique. The mean iron content in polymorphonuclear cells (PMNs) was 32 (SD 3) micrograms/g dry weight and in platelets 11 (2.6) micrograms/g dry weight. Corresponding values for age and sex matched healthy controls were 5.2 (1.9) and 4.6 (0.8) micrograms/g (p less than 0.001). Significant correlations were found in the patient group between (PMN) iron and the circulating levels of transferrin, total iron, and lactoferrin (p less than 0.05). PMN iron was not related to serum ferritin. Platelet iron correlated with transferrin (p less than 0.01) but not with the other iron binding proteins. Significant relationships were also found between the PMN iron stores and the inflammatory activity defined by erythrocyte sedimentation rate (ESR) and the immunoglobulins A and G. These data further illustrate the altered iron kinetics in chronic inflammatory disease and record the fact that the redistribution of iron associated with the inflammatory process also includes granulocytes and platelets.

Blood Platelets↗

The selection and evaluation of new chelating agents for the treatment of iron overload.

A large-scale systematic evaluation of potential iron chelators for the treatment of hemosiderosis was conducted. The compounds were identified and evaluated using a hypertransfused mouse screen in which deferrioxamine B was a standard. This screen was designed to measure iron depletion in the tissues as well as iron excretion. Groups of 10 previously hypertransfused BDF1 male mice received a single daily i.p. injection of either vehicle, standard, or test compound for 7 days. Iron in daily urine pools and individual spleen and liver homogenates was determined by atomic absorption. More than 70 chelators were evaluated, including natural and synthetic hydroxamic acids, phenols, catechols and tropolones known to have a high affinity for iron (III) in vitro. Ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) was shown to be considerably more effective than deferrioxamine B (i.p.) and, in addition, was orally active. Factors determining the efficacy of this and other chelating agents are discussed.

Animals↗