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

Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.
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PMID:Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease. 811 Oct 53

Several life-threatening complications of the common disorder sickle cell disease require management with red blood cell transfusions and, hence, long-term iron-chelating therapy. The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) has not previously been determined in patients with sickle cell disease. We compared the efficacy of L1 to that of standard-dose subcutaneous deferoxamine in four regularly transfused patients with homozygous sickle cell disease, who had evidence of severe iron overload and a history of poor compliance with deferoxamine. Determination of 24-hour urinary iron excretion conducted over 5 days immediately after transfusion showed that the mean daily urinary iron excretion induced by L1 at 75 mg/kg/d (0.48 +/- 0.23 mg/kg) was equivalent to that induced by deferoxamine at 50 mg/kg/d (0.39 +/- 0.06 mg/kg). In two of three patients studied, a significant (P < .025) increase in mean daily urinary iron excretion was achieved when the dose of L1 was increased to 100 mg/kg/d. Total iron balance studies, which quantitated both urinary and stool iron excretion on L1 and deferoxamine, determined that mean total daily iron excretion induced by deferoxamine (0.88 +/- 0.05 mg/kg) was significantly greater (P < .05) than that induced by L1 (0.53 +/- 0.17 mg/kg), attributable to the significantly greater stool iron excretion during deferoxamine treatment (0.50 +/- 0.16 mg/kg/d) compared with that measured during L1 treatment (0.12 +/- 0.08 mg/kg/d, P < .01). Stool iron excretion accounted for a significantly greater percentage of total iron excretion during deferoxamine treatment (59% +/- 20%) than during L1 treatment (23% +/- 14%, P < .01). These iron balance studies are the first to compare total iron excretion induced by L1 with that achieved by deferoxamine. They demonstrate that the mean total daily iron excretion during L1 treatment (0.53 +/- 0.17 mg/kg) is sufficient to maintain net negative iron balance in most regularly transfused patients with sickle cell disease. Because long-term compliance with L1 has been shown previously to be superior to that with deferoxamine in patients with homozygous beta-thalassemia, the use of L1 should increase the long-term effectiveness of iron chelation in patients with sickle cell disease.
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PMID:Iron-balance and dose-response studies of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease. 816 1

A five year prospective observational study was initiated in 1985 at Howard University to describe the nutritional, clinical, dietary, lifestyle, environmental, and socioeconomic characteristics of women who enrolled in the hospital prenatal clinic. The participants were nulliparous, between the ages of 18 and 35 years, free of diabetes and abnormal hemoglobins (sickle cell disease, thalassemia, and hemoglobin C), and had been admitted prior to the 29th week of gestation. During the three year period from 1985-1988, the incidence of low birth weight (LBW) in 239 deliveries to project participants was 8.3%, whereas that of women simultaneously enrolled in the prenatal clinic with the same eligibility requirements, but not recruited for the research project, was 21.9% (P = 0.001). The incidence of LBW in infants of African American women with these eligibility requirements who were delivered by private physicians but were not enrolled in the project, was 6.3%. The reduction in LBW of infants delivered to participants in this study is attributed to the enhanced social and psychological support by project staff during their pregnancies. The caring, sensitive demeanor of the research project staff may have empowered the participants to (a) give greater compliance (91 vs. 70%) in the ingestion of the routine physician-prescribed vitamin/mineral supplement, which provided nutrients low (less than 70% of the 1989 RDAs) in their customary diets, such as folate, pyridoxine, iron, zinc, and magnesium and (b) show greater accountability in keeping prenatal clinic appointments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple factors as mediators of the reduced incidence of low birth weight in an urban clinic population. 820 43

To further define the nature of abnormal iron deposits on the membranes of pathologic red blood cells, we have used sickle cell anemia (HbSS), HbSC, and beta-thalassemic erythrocytes (RBCs) to prepare inside-out membranes (IOM) and insoluble membrane aggregates (AGGs) containing coclustered hemichrome and band 3. Study of IOM from HbSC and thalassemic patients showed that amounts of heme iron and, especially, free iron were much higher in patients who had undergone surgical splenectomy. The membrane AGGs from HbSS and beta-thalassemic RBCs contained much more globin than heme, with this discrepancy being variable from patient to patient. Although these AGGs were enriched (compared with the ghosts from which they were derived) for heme, as expected, less than 10% of total ghost heme was recovered in them. Remarkably, these AGGs also were enriched for nonheme iron, markedly so in some patients. Iron binding studies showed that the association of free iron with these hemichrome/band 3 AGGs is explained by the fact that free iron binds to denatured hemoglobin. These results document that free iron is nonrandomly associated with the membranes of sickle and beta-thalassemic RBCs. Whether this plays a causative role in the premature removal of such cells from the circulation remains to be seen.
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PMID:Nonrandom association of free iron with membranes of sickle and beta-thalassemic erythrocytes. 821 9

Thirteen patients with sickle cell disease (SCD) undergoing transfusion therapy and 8 control patients were examined by magnetic resonance imaging to discriminate bone marrow change due to iron deposition from hematologic marrow hyperplasia. Using T1-weighted spin echo images, only two subjects showed extremely low signal intensity marrow compatible with iron deposition. However, using T2-weighted fast spin echo images with fat suppression, cranial bone marrow in SCD patients with transfusion therapy showed considerably lower signal than that of controls. The main cause of marrow signal decrease in SCD patients with transfusion therapy was considered to be iron deposition due to repeated transfusion therapy rather than red marrow hyperplasia.
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PMID:Iron deposition in cranial bone marrow with sickle cell disease: MR assessment using a fat suppression technique. 825 45

The effect of riboflavin supplementation (5mg twice daily for 8 weeks) on reduced blood glutathione (GSH) and iron status was assessed in 18 patients with sickle cell disease (SCD-HbSS). Twelve SCD patients and 13 normal (Hb-AA) subjects served as the control. The total iron binding capacity (TIBC) and serum ferritin (SF) were significantly higher (p < 0.01), but GSH level, haemoglobin and transferrin saturation (TS) were significantly lower (p < 0.001) in SCD patients than in normal subjects. The administration of riboflavin elicited a significant increase (p < 0.01) in serum iron and TS but a non significant increase in SF and circulating Hb. The GSH level varied little in riboflavin supplemented but decreased significantly in unsupplemented SCD. The disparity in GSH concentration might reflect availability of FAD for regeneration of GSH from glutathione. Likewise, the haematological improvement in the supplemented group supports the assertion that riboflavin enhances erythropoiesis. For an effective management of SCD in Africa, a closer attention should be directed to the riboflavin status in haemolytic disorders.
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PMID:Clinical trial of riboflavin in sickle cell disease. 829

Transfusion-induced hemosiderosis is a serious and potentially life-threatening complication for some patients with sickle cell anemia. The use of high-dose intravenous deferoxamine (DFO) has become widespread in spite of a paucity of published data on safety and efficacy. We report a randomized double-blind study of the dose-response relationship of intravenous DFO in six subjects with sickle cell anemia and severe transfusion-induced hemosiderosis (serum ferritin 4100 to 14,176 ng/ml). Each subject received three different doses of intravenous DFO for 3 days each while consuming a constant diet. Total iron excretion (urine and fecal) was 91% greater at 180 mg/kg/day DFO than at 60 mg/kg/day DFO, and fecal iron excretion became a relatively larger proportion of total excretion at higher doses. Subsequent treatment for 3 months with 150 mg/kg/day DFO caused a 33% to 60% reduction in serum ferritin and demonstrable improvement in hepatic function in all patients. No toxicity was encountered, but DFO at 180 mg/kg/day was associated with a significant increase in fecal zinc excretion when compared with that observed at lower doses.
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PMID:Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship. 832 Apr 90

After the development of monophasic combined oral contraceptives (COCs), containing a fixed dose of estrogen and progestogen, biphasic and triphasic COCs were introduced in the 1980s; in these the dose of ethinyl estradiol and progestogen changes during the pill cycle. In the so-called every day pills, the 21 pills of active steroid combination are followed by 7 inactive pills containing starch, iron, or bran. Method failures of OCs are among the lowest ranging from 0.2-1/100 woman-years. User failures can be as high as 6.2/100 women-years. The individual difference in peak plasma levels of estrogens in women taking identical OCs can be 10-fold. Conditions that affect the bioavailability of contraceptive steroids are: 1) drug interaction (vitamin C, drugs that induce liver enzymes, and antibiotics); 2) vomiting; 3) vegetarianism; 4) missing pills; and 5) malabsorption. Metabolic effects of COCs pertain to carbohydrate metabolism, lipid metabolism, hemostasis, and vitamins. Prescribing of COCs involves counseling clients about contraindications to COCs, starting routines, and the pill-free interval, as well as follow-up and monitoring, the problem of missing pills, and selection criteria for OC use. Medical conditions in which COC use requires special consideration are sickle cell disease, trophoblastic disease, HIV disease, gallstones, epilepsy, valvular heart disease, oligomenorrhea/amenorrhea, inflammatory bowel disease, and surgery. Side effects of COCs may include depression, nausea, vomiting, headaches, urinary tract infection, and lower genital tract infections. 6 months after stopping the OC 1% of users become amenorrheic. Many of the common causes of amenorrhea, such as weight loss amenorrhea and polycystic ovarian disease, may be treated with the COC until the couple desires to have a baby. The new progestogens desogestrel, norgestimate, and gestodene are highly selective compared to first and second generation progestogens.
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PMID:Combined oral contraceptives: acceptability and effective use. 832 4

In this paper we have reviewed the social and technical aspects of carrier screening and prenatal diagnosis of the inherited haemoglobinopathies. The characteristics of programmes based on carrier screening and prenatal diagnosis ongoing in a number of at-risk Mediterranean populations have been described. The most relevant and common aspects of these programmes are the continuous educational campaign directed to the population at large, the voluntary basis and non-directive counselling. The target population has been most commonly couples before or after marriage. The vast majority of couples counselled accepted prenatal diagnosis. All programmes have encountered a high degree of success as indicated by the marked reduction in the birth rate of infants with thalassaemia major. No significant adverse effects have been reported. A programme with similar characteristics and for which the preliminary results are encouraging, is operating for sickle cell anaemia in the Cuban population. In a population with high frequency of hydrops fetalis, screening for deletion alpha-thalassaemia is recommended to prevent the negative effects on a pregnant woman of the presence of an hydropic fetus. Thalassaemia carrier screening is now carried out by automatic red cell indices and HbA2 determination. Definition of atypical cases may require iron studies, globin chain synthesis determination and/or alpha, beta- and delta-globin gene analysis. Identification of the carrier state is followed by definition of the mutation on enzymatically amplified DNA. Known mutations may be detected by restriction endonuclease analysis, non-denaturing polyacrylamide gel electrophoresis, allele-specific primers or allele-specific probes. The most promising procedures, which are also amenable to complete automation are reverse oligonucleotide hybridization and primer-specific amplification. Unknown mutations are defined by denaturing gradient gel electrophoresis, single-strand conformation polymorphism analysis, and chemical mismatch cleavage analysis followed by direct sequencing. The same methods on enzymatically amplified chorionic villus DNA are used for prenatal diagnosis. The potential pitfall resulting from maternal contamination can be avoided by careful dissection of the maternal decidua from the chorion and by the simultaneous amplification of a suitable polymorphism.
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PMID:Screening and prenatal diagnosis of the haemoglobinopathies. 839 56

To examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75, P < 0.0001) and in those with thalassemia major (R = 0.76, P < 0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76, P < 0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only approximately 57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores.
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PMID:Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. 841 2


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