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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron chelation with deferoxamine was studied in ten patients with sickle cell anemia who had received 2 to 37 liters of red blood cells. Urinary excretion of iron in response to 1.5 gm of deferoxamine administered intravenously ranged from 5.9 to 28.7 mg/24 hours and was closely related to the amount of iron acquired from transfusions. Administration of ascorbic acid did not improve deferoxamine-induced excretion of iron. Urinary excretion of iron in response to 0.75 gm of DFO intramuscularly was 4.7 to 6.9 mg/24 hours in three patients who had received 15 to 37 liters of red cells. The data indicate that measurement of DFO-induced excretion of iron is of value in detecting increased iron stores in children with sickle cell anemia who have received repeated transfusions and that chelation therapy will retard the accumulation of iron.
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PMID:Excretion of iron in response to deferoxamine in sickle cell anemia. 63 13

Total body iron burden was estimated by two indirect methods in 23 patients with sickle cell anemia. Concentrations of serum ferritin correlated directly and significantly with age of the patients. Eleven of 15 patients under 20 years of age had normal levels of serum ferritin. Deferoxamine-induced urinary excretion of iron was considerably less than that reported in patients with thalassemia major who were receiving regular blood transfusions. These data imply that patients with sickle cell anemia generally do not acquire excessive iron burdens during the first two decades of life. The risks of transfusional hemosiderosis in patients with sickle cell anemia who are included in hypertransfusion programs are discussed.
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PMID:Iron burden in sickle cell anemia. 63 16

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.
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PMID:[Treatment of post-transfusion iron overload by deferoxamine]. 273 4

Red blood cell (RBC) membranes from patients with the thalassemic and sickle hemoglobinopathies carry abnormal deposits of iron presumed to mediate a variety of oxidative-induced membrane dysfunctions. We hypothesized that the oral iron chelator deferiprone (L1), which has an enhanced capacity to permeate cell membranes, might be useful in chelating these pathologic iron deposits from intact RBCs. We tested this hypothesis in vitro by incubating L1 with RBCs from 15 patients with thalassemia intermedia and 6 patients with sickle cell anemia. We found that removal of RBC membrane free iron by L1 increased both as a function of time of incubation and L1 concentration. Thus, increasing the time of incubation of thalassemic RBCs with 0.5 mmol/L L1 from 0.5 to 6 hours, enhanced removal of their membrane free iron from 18% +/- 9% to 96% +/- 4%. Dose-response studies showed that incubating thalassemic RBC for 2 hours with L1 concentrations ranging from 0.125 to 0.5 mmol/L resulted in removal of membrane free iron from 28% +/- 15% to 68% +/- 11%. Parallel studies with sickle RBCs showed a similar pattern in time and dose responses. Deferoxamine (DFO), on the other hand, was ineffective in chelating membrane free iron from either thalassemic or sickle RBCs regardless of dose (maximum, 0.333 mmol/L) or time of incubation (maximum, 24 hours). In vivo efficacy of L1 was shown in six thalassemic patients whose RBC membrane free iron decreased by 50% +/- 29% following a 2-week course of L1 at a daily dose of 25 mg/kg. As the dose of L1 was increased to 50 mg/kg/d (n = 5), and then to 75 mg/kg/d (n = 4), 67% +/- 14% and 79% +/- 11%, respectively, of their RBC membrane free iron was removed. L1 therapy--both in vitro and in vivo--also significantly attenuated the malondialdehyde response of thalassemic RBC membranes to in vitro stimulation with peroxide. Remarkably, the heme content of RBC membranes from L1-treated thalassemic patients decreased by 28% +/- 10% during the 3-month study period. These results indicate that L1 can remove pathologic deposits of chelatable iron from thalassemic and sickle RBC membranes, a therapeutic potential not shared by DFO. Furthermore, membrane defects possibly mediated by catalytic iron, such as lipid peroxidation and hemichrome formation, may also be alleviated, at least in part, by L1.
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PMID:Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. 765 28

We report four sickle cell anemia patients who have received multiple blood transfusions and have been non-compliant on Desferal chelation therapy. Abdominal ultrasonography demonstrated an echogenic pancreas in all four patients. Magnetic resonance imaging in three patients revealed decreased signal intensity in all sequences in the pancreas and liver. All four patients had marked iron deposition on liver biopsy. To our knowledge, increased echogenicity of the pancreas secondary to hemosiderosis (2 degrees hemochromatosis) in sickle cell patients has not been reported in the radiologic literature.
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PMID:Transfusional hemosiderosis in sickle cell anemia: another cause of an echogenic pancreas. 851 39

Red blood cells (RBCs) from patients with sickle cell anemia and thalassemia carry abnormal accumulations of molecular Fe(III) at the cytosol/membrane interface. The avidity of the red cell membrane for this iron has not been defined. Using open ghost membranes prepared from sickle RBC, we examined the ability of membrane-associated Fe(III) to resist removal by 15 chelators representing a 40-log range of affinities for Fe(III). Efficacy of chelators was compared with literature values for their idealized affinity for iron as represented by the cummulative stability constant (beta n), their effective stability constant reflecting affinity under biologic conditions (Keff), and an indicator of their ability to chelate Fe(III) in the presence of an insoluble phase of iron (Ksol). Deferoxamine, a very high affinity chelator having log beta n = 30.6, was found to be the lowest affinity chelator able to remove RBC membrane Fe(III). Regardless of chelator beta n, only those agents able to preserve log Keff > or = 12 were able to do so, indicating that the membrane's effective avidity for Fe(III) is on the order of 10(12). Additional confirmation that membrane avidity for Fe(III) is extremely high is found in the observation that only chelators having log Ksol > 0 were effective. Potential physiologic iron chelators in cytoplasm of pathologic red cells are unable to prevent or reverse iron accumulation on the membrane because they do not have sufficiently high affinity for iron. These data argue that RBC membrane Fe(III) is truly pathologic.
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PMID:Extremely high avidity association of Fe(III) with the sickle red cell membrane. 870 94

Sickle-cell anemia is one of the most common hemoglobinopathies. The therapy consists of symptomatical measures like giving analgetics, decreasing blood viscosity, and red cell transfusions. We present a cascuistic of a 23-year-old Turkish female patient with a homozygous form of sickle-cell disease, who was treated with analgetics, multiple red blood cell transfusions and Desferal because of severe pain crises. From November 1992 until June 1993 we performed automated red cell exchange transfusions with six fresh, washed and leukocyte-depleted red blood cell units with a continuous flow cell separator (Cobe Spectra). We propose to prefer the exchange with the cell separator to the conventional transfusion therapy by manual exchange or a chronic transfusion program in severe sickle-cell crises.
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PMID:[Effective erythrocyte exchange by means of a cell separator in sickle cell anemia]. 948 Jan 28

Chronic red blood cell transfusion can prevent many of the manifestations of sickle cell disease. The medical costs of chronic transfusion and management of associated side effects, especially iron overload, are considerable. This study was undertaken to evaluate the financial impact of chronic transfusion for stroke prevention in patients with sickle cell anemia. Outpatient charges pertaining to hospital-based Medicare uniform bill (UB-92) codes, professional fees, and iron chelation were evaluated. Data were collected on 21 patients for a total of 296 patient months (mean, 14; median, 14 months/patient). Charges ranged from $9828 to $50 852 per patient per year. UB-92, chelation, and physician-related charges accounted for 53%, 42%, and 5% of total charges, respectively. Of UB-92 charges, 58% were associated with laboratory fees and 16% were related to the processing and administration of blood. Charges for patients who required chelation therapy ranged from $31 143 to $50 852 per patient per year (mean, $39 779; median, $38 607). Deferoxamine accounted for 71% of chelation-related charges, which ranged from $12 719 to $24 845 per patient per year (mean, $20 514; median, $21 381). The financial impact of chronic transfusion therapy for sickle cell disease is substantial with charges approaching $400 000 per patient decade for patients who require deferoxamine chelation. These data should be considered in reference to cost and efficacy analyses of alternative therapies for sickle cell disease, such as allogeneic bone marrow transplantation.
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PMID:Financial analysis of chronic transfusion for stroke prevention in sickle cell disease. 1100 85

We designed a study to obtain follow-up on behavioral aspects of compliance with home deferoxamine administration, explore social factors that might influence compliance, and evaluate the effectiveness of a pilot intervention program for patients with thalassemia or sickle cell disease who were receiving chronic transfusion therapy. Thirty-one patients between the ages of 6 and 21 years and their primary caregivers were administered a 24-hour recall Interview about home care. Fifteen went on to participate in a Desferal Day Camp, which combined educational strategies with peer support. Behavioral measures of treatment adherence were similar for most patients with sickle cell disease and thalassemia. Patient compliance with days of deferoxamine administration at follow-up was associated with initial compliance, perceived support, and patient and caregiver knowledge. Increased sharing of responsibilities for home care by patients and caregivers and caregiver knowledge were associated with lower ferritin and liver iron levels. A subsample of 3 patients who were extremely noncompliant with days of deferoxamine administration was examined separately; these patients were found to be moderately compliant with the number of hours and amount of deferoxamine administered and to share fewer home care tasks with primary caregivers. Participation in Desferal Day Camp did not result in increases in knowledge or peer support, suggesting that future interventions should focus on family support and on improving self-regulatory skills. The crucial role of collaboration among patients, families, and health care providers in developing interventions to enhance adherence was emphasized.
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PMID:Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. 1120 66

In this review, current concepts and goals of iron chelation therapy for thalassemias, sickle cell disease, and myelodysplastic syndromes are discussed. The primary goal of iron chelation therapy is to prevent the accumulation of iron reaching harmful levels by matching iron intake from blood transfusion, with iron excreted by iron chelation. Over 30 years of experience with deferoxamine has shown iron chelation to be an effective therapeutic modality. However, chelation efficiency is limited because most of the body's iron stores are not directly chelatable, and only a small fraction of body iron is chelatable at any moment. Once iron has been deposited in organs other than the liver, for example the heart, removal by chelation is slow and inefficient. Chelation efficiency can be improved by designing regimes where chelators are available 24 hr a day to bind labile iron pools in cells and plasma. Deferoxamine has a short plasma half-life and the parenteral infusions required to achieve steady plasma levels are demanding, with consequent variable adherence to therapy. Once-daily oral administration of deferasirox achieves continuous chelation with trough concentrations sufficient to decrease plasma labile iron species progressively, and achieves an efficiency of chelation not obtainable with deferiprone or deferoxamine monotherapy.
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PMID:Concepts and goals in the management of transfusional iron overload. 1796 73


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