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

In a national longitudinal-cohort study of 59,462 end-stage renal disease (ESRD) patients, we examined dosing and effectiveness of erythropoietin (EPO) during the first year of its use in clinical practice (July 1989 through June 1990). In unadjusted and multivariate analyses of Medicare claims data, the mean dose of EPO prescribed was: relatively small and similar for initial and maintenance therapy, 2752 (95% confidence interval 2740 to 2764) and 2668 (95% confidence interval 2654 to 2682) units, respectively; lower when initial therapy was started later (591 units lower in September 1989 and 760 units lower in November 1989 vs. July 1989, P < 0.0001); lower by 135 units during initial therapy and by 116 units during maintenance therapy for females (who weigh less) compared to males (P < 0.001); and lower by 400 units for patients treated in for-profit versus not-for-profit centers. In multivariate analysis: hematocrit response was less and mean maintenance dose was 298 units and 621 units greater for patients whose ESRD was due to multiple myeloma and sickle cell disease, respectively, compared to those with hypertension-related ESRD (P < 0.01); and hematocrit response was logarithmically related to dose [hematocrit = 0.97 ln (dose), P < 0.0001]. Forty-four percent of patients had a hematocrit > or = 30 after four months of therapy. The percent of patients transfused during three month periods before and after therapy decreased from 20% to 5%, respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early dosing practices and effectiveness of recombinant human erythropoietin. 851 Mar 92

Erythropoiesis is increased in cultures of human blood progenitors when oxygen tension is reduced from 20% (room air) to 5% (low oxygen, closer to physiological bone marrow levels). The effects of low oxygen on gamma-globin synthesis and colony growth in methyl cellulose cultures of blood mononuclear cells from normal individuals and patients with sickle cell diseases were examined. Low oxygen increased colony numbers by 1.5- to 2-fold and erythropoietin sensitivity by almost 2-fold. The interval required for maximal colony growth in cultures from patients with sickle cell disease (sickle colonies) was reduced from 17 days in 20% oxygen to 13 days in 5% oxygen. Relative synthesis of gamma-globin was examined by labeling with 3H-leucine and electrophoresis on Triton acid urea polyacrylamide gels. The % gamma was 1.7-fold higher in normal and 1.4-fold higher in sickle cultures on day 13 in low oxygen. On day 16 the expected temporal decline was not seen in low oxygen, and the % gamma was 2-fold higher in normal and 1.8-fold higher in the sickle studies. Hemin increased colony growth and gamma-globin synthesis in normal cultures in air, and the effects of hemin and low oxygen were additive. In sickle cultures, hemin and low oxygen had additive effects on colony growth, but only low oxygen increased gamma-globin synthesis. Interleukin-3 increased colony numbers on day 13, primarily by acceleration of peak growth. Interleukin-3 also increased gamma-globin synthesis in low oxygen in normal but not sickle cultures. Thus, low oxygen increases in vitro sensitivity to erythropoietin, colony numbers, and relative gamma-globin synthesis in normal and sickle cultures.
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PMID:Low oxygen enhances sickle and normal erythropoiesis and fetal hemoglobin synthesis in vitro. 853 30

The spectrum of anemias treated with recombinant human erythropoietin is rapidly broadening. Lifelong treatment with very high doses is now under evaluation for beta-thalassemia and sickle cell anemia. These indications make it worthwhile to search for methods that will allow a permanent systemic delivery of the hormone. Here, we review experimental gene-transfer-based procedures for erythropoietin delivery in vivo. In mice, both ex vivo and direct in vivo approaches for gene transfer have resulted in the long-term production of therapeutic levels of the hormone. Gene transfer of erythropoietin could become a viable alternative to the injection of the purified recombinant protein once reliable procedures for controlling transgene expression are available.
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PMID:Gene transfer for erythropoiesis enhancement. 879 20

Our purpose is to illustrate our contributions to the study of the haemoglobinopathies observed in Belgium. We described a new deletion leading to major thalassaemia and have established that the erythropoietin production is adequate in this disease. We were particularly interested in some manifestations of iron overload (polyendocrinopathy, roles of the decreased phagocytosis and of the desferrioxamine therapy in the predisposition to infections, protective role of desferrioxamine in the protection against the progression of HIV-1 infection). The prevention of thalassaemia major has deserved our particular attention. As concerns sickle cell anemia, we have underlined some particular aspects of the clinical expression of the disease. The use of new therapeutic approaches (bone marrow transplantation, hydroxyurea) has also been outlined.
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PMID:[Study of hemoglobinopathies found in Belgium]. 884 87

Chronic leg ulcers may result from vasoocclusive complications associated with the decreased oxygen-carrying capacity of hemoglobin in patients with sickle cell disease or its variants. Nonsurgical management includes the use of anti-sickling drugs and chemical manipulation of the hemoglobin composition. It has been suggested that the use of recombinant human erythropoietin (r-HuEPO) may help by stimulating proliferation of red blood cell precursors; it also has been proposed that r-HuEPO may act as a growth factor to non-hematologic tissues. Surgical management is a choice of last resort, often requiring microsurgical techniques, such as free-flap transfer.
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PMID:Leg ulcers in patients with sickle cell disease. 906 48

The mechanism of resistance to recombinant human erythropoietin (EPO) in hemodialysis patients with hemoglobinopathy is not yet fully understood. Poor responses to EPO have been reported in anemic dialysis patients with sickle cell disease and thalassemia. We present the first case of a hemodialysis patient with EPO resistance and hemoglobin J-Meinung, which is initially found by hemoglobin electrophoresis and finally proven by molecular genetic analysis. Additionally, the patient was diagnosed as having chronic active hemolysis with hallmarks of splenomegaly, an increased serum bilirubin and reticulocyte index, and a reduced haptoglobin level. We discuss the possible mechanisms and proper treatment options in such patients with a poor response to EPO.
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PMID:Resistance to recombinant erythropoietin in a hemodialysis patient with heterozygous hemoglobinopathy J-Meinung. 915 14

Anemia with a relatively low erythropoietin level has been described in several medical conditions associated with chronic inflammatory diseases such as rheumatoid arthritis, cancer, sickle cell disease, chronic renal failure, acquired immunodeficiency syndrome, and severe autonomic nervous system failure. This case report describes the development of anemia with a relatively low erythropoietin level in a 65-year-old man with non-insulin-dependent diabetes mellitus, normal renal function, and negative hematologic, thyroid, and autoimmune disease work-ups. The serum erythropoietin level was 14 mU/mL (N: 10-20 mU/mL). The hemoglobin was 7.5 g/dL and the hematocrit was 24%. The patient was treated with recombinant erythropoietin at 50 U/kg subcutaneously three times weekly. The hemoglobin level increased over a 4-week period. When erythropoietin was stopped, the anemia recurred in 2 months. We conclude that the patient's anemia was caused by a relative lack of endogenous erythropoietin release. The exact mechanism of this anemia is unknown. We recommend including a test for erythropoietin level in the evaluation of any unexplained anemia.
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PMID:Anemia secondary to low erythropoietin in a patient with normal renal function. 936 36

The ability of circulating progenitor cells from 22 patients with sickle cell disease (SCD) to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin). In both conditions, SCD patients presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5x10[5]MNC) when compared to control subjects. The study of the expression of erythropoietin receptors revealed an increased level in SCD patients. Moreover, there was a correlation between both stimulated and autocrine (without stimulus) BFU-E and the expression of erythropoietin receptors. These results are of particular interest since they indicate that the phenomenon of spontaneous BFU-E-derived colonies observed in SCD patients may be due to an increased expression of erythropoietin receptors.
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PMID:Early circulating erythroid progenitor cells and expression of erythropoietin receptors in sickle cell disease. 957 75

Hydroxyurea (HU) induces HbF production and can reduce painful crises in some patients with sickle cell anemia (SS). However, HbF induction alone cannot explain the beneficial effect of HU treatment as some patients experience clinical improvement while showing only minor increases in HbF. Other actions of HU, in particular its effects on vascular endothelium, adhesion molecule expression and cytokine production may also play a role in the final therapeutic outcome. In order to analyze these effects we studied the levels of interleukin-3 (IL-3), interleukin-6, granulocyte-macrophage colony-stimulating factor, erythropoietin, stem cell factor, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule-1, soluble E-selectin and soluble P-selectin in 7 SS patients before and during 5 months of HU treatment. Use of HU seems to have no detectable effect on soluble adhesion molecules, but the steady state levels of soluble vascular adhesion molecule-1 are enhanced in SS patients compared to normal controls. Of the cytokines studied, only IL-3 showed an increase during therapy, suggesting HU may induce early erythroid progenitors capable of producing HbF by a direct or indirect effect on IL-3 production. Remarkably, the steady state stem cell factor levels in sickle cell patients seemed to be decreased compared to healthy controls.
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PMID:Cytokines and soluble adhesion molecules in sickle cell anemia patients during hydroxyurea therapy. 969 Nov 43

In the management of patients requiring chronic transfusion, various parameters may be used to evaluate the degree of erythroid marrow suppression. The aim of our study was to assess which of these parameters provide the most useful assessment of erythropoiesis. We studied 27 chronically transfused patients, 19 with sickle cell disease (SS patients) and 8 with thalassemia. Thirty-one nonchronically transfused SS patients and 74 healthy children served as controls. We measured serum transferrin receptor levels, reticulocyte counts, hemoglobin (Hb) concentrations and erythropoietin levels. The serum transferrin receptor levels were very elevated in control SS patients and remained significantly elevated in those on transfusion therapy, but were normal in thalassemia patients, indicating a more complete suppression of erythropoiesis. The reticulocyte counts were elevated in all SS patients, even when on chronic transfusion, but were in the normal range in patients with thalassemia. Erythropoietin levels were elevated in patients with thalassemia and in all the SS patients. Hb levels negatively correlated with serum transferrin receptor and erythropoietin in all SS patients. In the transfused SS patients, a higher HbS level correlated with higher reticulocyte counts, transferrin receptor, and erythropoietin levels. In thalassemia patients, erythropoiesis was more completely suppressed, as reflected both by normal reticulocyte counts and near-normal transferrin receptor levels. Though the reticulocyte counts were not significantly different in the transfused SS patients, the serum transferrin receptor levels were less elevated than in SS patients not on transfusion. The serum transferrin receptor level appears to be the most useful marker of marrow erythropoietic activity in chronically transfused SS patients. We recommend that reticulocyte counts be integrated with periodic measurements of serum transferrin receptor levels.
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PMID:Serum transferrin receptor as a marker of erythropoiesis suppression in patients on chronic transfusion. 992 3


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