Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The release of free, reactive iron from cellular iron stores has been implicated as an important contributor to tissue damage in a variety of clinical situations, including ischemia and reperfusion injury, hemorrhagic shock, and burn injury. Deferoxamine mesylate (DFO), the only iron chelator currently approved for clinical use, is used for the treatment of iron overload, including acute iron poisoning and treatment of chronic iron overload in transfusion-dependent anemias such as beta-thalassemia. However, it is not suitable for acute care situations because of its toxicity, primarily hypotension when given at high intravenous doses, and its short plasma half-life. We have produced a high-molecular-weight iron chelator by chemically coupling DFO to hydroxyethyl starch. This novel chelator (HES-DFO) was administered to healthy male subjects by intravenous infusion over a 4-hour period. The drug was well tolerated, and signs of DFO acute toxicity were not observed. Maximum plasma chelator levels of approximately 3 mmol/L were achieved with HES-DFO, which is more than an order of magnitude higher than has been reported with injections of DFO. Drug residence time in plasma was markedly prolonged, with an initial half-life of 22 to 33 hours. Urinary iron excretion was 7.1 +/- 2.2 mg in 48 hours in the highest dose group, as compared with 0.06 +/- 0.15 mg in control subjects who received normal saline infusions. Intravenous infusion of HES-DFO is well tolerated, produces substantial and prolonged plasma chelator levels, and markedly stimulates urinary iron excretion.
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PMID:First human studies with a high-molecular-weight iron chelator. 1063 95

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs.
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PMID:Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States. 1792 47