Korean Guideline for Iron Chelation Therapy in Transfusion-Induced Iron Overload

Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in malaysian Chinese β-thalassaemia major patients / La terapia de quelación con deferoxamina no normaliza los niveles de ferritinaa pero atenúa el daño oxidativo y mejora el nivel antioxidante total en los pacientes sinomalayos que padecen de talasemia β

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in β-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxaminechelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese β-thalassaemia major patients.

La beta-talasemia mayor causa anemia severa, y los pacientes con este padecimiento pueden hacerse dependientes de las transfusiones de sangre por el resto de sus vidas. Las transfusiones regulares de sangre dan lugar a una sobrecarga de hierro que conduce al dano oxidativo, el cual a su vez puede acelerar la mortalidad. El objetivo de esta investigación fue estudiar las tasas de oxidantesantioxidantes en pacientes de beta-talasemia mayor en el Centro Médico de la Universidad de Malaya, tanto aquellos bajo tratamiento de quelación con deferoxamina, como aquellos sin terapia de quelación alguna. Se recogieron muestras de sangre de 39 pacientes chinos y 20 controles. Se extrajeron plasma y lisados de celulas mononucleares perifericas (CMSP), y se realizaron pruebas bioquimicas para evaluar el estrés oxidativo. El estrés oxidativo era evidente en estos pacientes en forma de productos avanzados de oxidación de proteinas (PAOP), y los hidroperoxidos de lipidos eran elevados, en tanto que la actividad de glutatión peroxidasa y el poder reductor ferrico/antioxidante (FRAP) era reducida. La actividad de la catalasa en los pacientes de CMSP era elevada, posiblemente como un mecanismo compensatorio frente a la actividad de glutatión peroxidasa reducida tanto en los globulos rojos como en las CMSP. Los niveles más bajos de FRAP y los más altos de PAOP en los pacientes no quelados en comparación con los pacientes quelados, indicaban un bajo nivel de estrés oxidativo en los pacientes quelados. Los niveles de ferritina tanto en los pacientes quelados como en los no quelados, eran altos, y los niveles promedio de actividades enzimaticas del higado fueron elevados en la mayoria de los pacientes, independientemente de la terapia de quelación. En conclusión, este estudio indica que la terapia de quelación con deferoxamina no normaliza el nivel de ferritina, pero en cambio atenua el daño oxidativo, y mejora el nivel antioxidante total en los pacientes sinomalayos afectados por la betatalasemia mayor.

Complete Hematopoietic Recovery after Continuous Iron Chelation Therapy in a Patient with Severe Aplastic Anemia with Secondary Hemochromatosis

A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.

Comparative effects of single and combined chelation therapy in chronic lead toxicity: role of reactive oxygen species

To investigate and compare the efficacy of different chelation therapies either single [CaNa[2]EDTA or meso-DMSA] or combined regimen [CaNa[2]EDTA + meso-DMSA] in the treatment of chronic lead acetate exposure and suggested role of reactive oxygen species [ROS] in the mechanism of lead toxicity. This study was carried out on thirty adult male albino rats classified into 5 groups [6 rats/each group] and subjected to the treatments with lead acetate in a dose of 5mg/kg daily for 6 weeks [i.p] for 6 weeks, then injected with CaNa[2]EDTA [0.3 mmol/kg daily, i.p.] for 2 consecutive weeks or meso-DMSA [0.5 mmol/kg daily, i.p.] for 2 consecutive weeks or both CaNa[2]EDTA 0.3 mmol/kg daily, [i.p.] and meso-DMSA [0.5 mmol/kg daily, i.p.] for 2 consecutive weeks. Lead was estimated by flame atomic absorption spectrometry, serum thiobarbituric acid reactive substances [TBA-RS], tissue TBA-RS, serum protein thiols [PrSH], tissues non-protein sulfhydryl compounds [NPSH], hemoglobin and serum creatinine were determined spectrophotometry. Brain glutathione peroxidase [GPx] was determined by high performance liquid chromatography [HPLC].Treatment of adult male albino rats with lead acetate produced significant increases in lead levels of serum, liver, kidney, brain and bone amounting to 205%, 126%, 152%, 275% and 133%, respectively as compared to control healthy group. Also, there were marked elevations in thiobarbituric acid reactive substances [TBA-RS] which are indicators of oxidative stress in serum, liver, kidney and brain calculated as 159%, 95%, 192% and 153%, respectively. In addition, serum protein thiol [PrSH] was decreased amounted to 32%. Meanwhile, there was marked decrease in non-protein sulfhydryl groups [NPSH] of kidney reaching 36%. Moreover, measured serum creatinine was significantly elevated recording 245%, whereas hemoglobin concentration was markedly decreased amounted as 23% in comparison with the control group. On the other hand, administration of each of the single chelating agents [calcium disodium ethylenediaminetetraacetic acid, CaNa[2]EDTA, i.p. in a dose of 0.3 mmol/kg daily for 2 consecutive weeks or meso-dimercaptosuccinic acid, meso-DMSA, i.p. in a dose of 0.5 mmol/kg daily for 2 consecutive weeks] and the combined chelation therapy [CaNa[2]EDTA 0.3 mmol/kg daily, i.p. and meso-DMSA 0.5 mmol/kg daily, i.p] for 2 consecutive weeks after lead acetate treatment resulted in significant ameliorating effects in the previous mentioned parameters. It is to be concluded that the reactive oxygen species play important roles in chronic lead toxicity. Moreover, each of meso-DMSA or the combined chelation therapy is more effective than CaNa[2]EDTA in reducing serum and brain lead levels as well as brain TBA-RS. However, the combined chelation therapy was more effective than meso-DMSA in decreasing serum TBA-RS; Effects that might be considered on choice of such chelating agents during chronic lead intoxication

Combined Treatment for Band Keratopathy

No abstract available.

The management of environmental lead exposure in the pediatric population: lessons from Clitty Creek, Thailand.

During the month of September-October 1997, a depression storm caused massive flooding in the area of western Kanchanaburi province, Thailand, causing lead-contaminated water from a nearby lead refinery plant to spill into the surrounding areas of Clitty Creek; exposing the village downstream to large amounts of lead. The Ministry of Public Health, together with the Ministry of Science, the Ministry of Industry, and officials from the Kanchanaburi Office of Public Health, began measures for environmental deleading and assessment of exposure and health risks of the population. METHOD: This was a retrospective cohort study of the effects that environmental remediation and chelation therapy had on the blood lead levels of children residing in Lower Clitty Creek Village during the period between 1997-2001. Sixty-eight children were followed yearly for their blood lead levels and hematocrit, beginning in early 1998. Simultaneously, programs for environmental remediation had begun. The blood lead levels (BLLs) of children were followed over a 3-year period. The BLLs during the 2 year period of environmental remediation alone were compared. Subsequently, when chelation therapy was instituted, levels pre and post chelation therapy, as well as the efficacy of the two different chelation methods were compared using standard 2-tailed t-test. RESULTS: The initial average BLL was 27.75 +/- 5.4 mg/dl (1998). After environmental remediation began, BLL at one year (1999) was 30.64 +/- 4.49 mg/dl (p = 0.072), and at two years (2000) was 30.30 +/- 5.1 mg/dl (p = 0.537). There were 18 children with BLLs > 25 who were elected to receive chelation therapy with CaNa2EDTA (11) and DMSA (7). Post chelation average BLL was 18.73 +/- 7.50 mg/dl. The difference between pre and post chelation BLL was statistically significant (p < 0.001: paired t-test). The differences in average BLLs between pre and post chelation for the EDTA group was 15.37 mg/dl and for the DMSA group it was 8.91 mg/dl. Children treated with EDTA appeared, on average, to have 6.47 mg/dl (p < 0.05: 95% CI (0.821-12.12)) lower BLL than those treated with DMSA. CONCLUSION: The incident at Clitty Creek serves to illustrate the importance of environmental remediation as a priority to treating lead poisoning in children. Only when effective environmental deleading has taken place can medical intervention in the form of chelation therapy begin.

Tratamiento de la insuficiencia arterial periférica con quelación / treatment of peripheral arterial insuficiency by means of chelation

A 100 pacientes con insuficiencia arterial periférica de los miembros inferiores por aterosclerosis comprobada mediante cirugía o angiografías fueron tratados con quelación con ácido etilendiaminotetracético. El estudio oscilográfico y el índice doppler tobillo-brazo realizados antes y después del tratamiento mostraron una diferencia estadística significativa con un aumento promedio del índice de 0.319 por lo que los autores lo proponen como una alternativa terapéutica en pacientes con ateroesclerosis severa