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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r-HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r-HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO.
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PMID:High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study. 222 80

Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. Circulating EPO levels in MDS patients were elevated, with a mean value approximately 35-fold higher than that of controls. The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone.
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PMID:In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes. 223 91

In a double-blind, placebo-controlled trial of rHu-EPO (recombinant human erythropoietin) comprizing 19 haemodialysis patients (rHu-EPO: n = 9, placebo: n = 10) the patients' opinion about the influence of the treatment on the quality of life was investigated. At the commencement of the trial and after eight weeks, a score was registered by means of a structured interview with a range of 0-10 concerning the complaints most frequently expressed by haemodialysis patients. Erythropoietin was effective in the treatment of renal anaemia. In the therapeutic group, the mean haematocrit value increased from 0.206 to 0.338 (p less than 0.0005), while no change in the haematocrit value was observed in the placebo group. In the therapeutic group, significant decreases were found in the interview scores for fatigue, vertigo (p less than 0.001), dyspnoea (p less than 0.0025), muscular weakness (p less than 0.01) and palpitations (p less than 0.05). No significant differences were found in the placebo group. The treatment had no serious side-effects. On the basis of this material, it is concluded that erythropoietin treatment of haemodialysis patients is effective and that a marked improvement in the quality of life can be observed already after treatment for eight weeks.
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PMID:[Quality of life of hemodialysis patients before and after erythropoietin therapy. A double-blind, randomized, placebo controlled study]. 223 69

The dose of recombinant human erythropoietin (r-HuEPO) required to correct the anemia of end-stage renal disease (ESRD) varies among patients. The response to r-HuEPO is impaired if absolute or relative iron deficiency exists. Aluminum may cause a microcytic anemia in patients with ESRD, but the mechanism remains incompletely defined. Twenty-two patients in the Canadian Multicentre EPO trial were studied for 6 months. In this randomized double-blind placebo-controlled trial, free erythrocyte protoporphyrin (FEP) was used as an indicator of iron-deficient deficient erythropoiesis. The relationship of FEP to the estimates of iron availability (serum iron, transferrin saturation, ferritin) and iron utilization (corrected reticulocyte count, hemoglobin) was evaluated by multiple linear regression analysis. The effect of aluminum on FEP was evaluated by adjusting the statistical model for this variable. All patients were iron replete as assessed by serum ferritin. FEP was not related to serum aluminum before administration of r-HuEPO, but it was significantly correlated with aluminum in the treated group. In hemodialysis patients treated with r-HuEPO, the proportion of the variability explained by the parameters of iron utilization and iron availability was 0.27. The effect of aluminum increased this to 0.59. In hemodialysis patients not receiving r-HuEPO, the proportion of variability in FEP explained by the model increased from 0.16 to 0.28 by adjusting for aluminum. The data support the hypothesis that aluminum interferes with the bioavailability of stored iron for erythropoiesis and thus may result in a microcytic anemia in patients with ESRD or may blunt their response to r-HuEPO therapy.
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PMID:Bioavailability of iron in hemodialysis patients treated with erythropoietin: evidence for the inhibitory role of aluminum. 223 35

Six splenectomized beagles of either sex (13.8 +/- 2.2 kg) were randomly treated either with 500 U/kg recombinant human erythropoietin (rhu-EPO) (verum group, n = 3) or an equivalent volume of the vehicle (placebo group, n = 3). Both solutions were given intravenously for 3 days. At day 4 after onset of treatment, the dogs were anesthetized and subjected to isovolemic hemodilution using 6% Dextran 60 (MW 60,000) down to a hematocrit of 0.10. During the recovery period vehicle or rhu-EPO was given every other day until the hematocrit reached control values. Every day venous blood samples were withdrawn, and the hematocrit as well as the concentrations of hemoglobin and 2,3-diphosphoglycerate were determined. In addition, the platelets and reticulocytes were counted. Treatment with rhu-EPO shortened the time of hematocrit recovery from 20 (placebo) to 11 days (p less than 0.05). The reticulocyte count peaked at day 2 (verum) versus day 5 (placebo). These findings indicate a successful stimulation of red blood cell production after extreme hemodilution in animals treated with erythropoietin. Therefore, rhu-EPO may allow to optimize blood donation programs as well as preoperative hemodilution and yield both, higher amounts of autologous blood and an accelerated reversal of dilutional anemia.
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PMID:Erythropoietin accelerates the recovery from extreme hemodilution: a randomized, placebo-controlled study in dogs. 226 48

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.
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PMID:Effect of recombinant human erythropoietin on renal function in humans. 229 99

Recombinant human erythropoietin (rHu-EPO) was given during 12 to 20 months in 15 long term haemodialysis anaemic (mean Hb: 6.6 +/- 1 g/dl) patients who required no blood transfusion. Patients over 65, or with severe arterial disease or with uncontrolled hypertension were not included in this trial. Correction of anaemia (mean Hb 12.1 +/- 0.6 g/dl) was achieved in all patients and maintained all along the study. An improved sense of wellbeing and increased exercise tolerance were reported by all patients. Appropriate maintenance dosage of rHu-EPO was 74 +/- 6 U/kg i.v. twice weekly. High dose oral and/or intravenous iron therapy was necessary in the absence of previous marked iron overload. One retinal venous thrombosis was the sole severe side-effect encountered. A slight but significant increase of blood pressure was observed with the need of intensifying previous anti-hypertensive therapy in one patient and of starting one in one another. Fine adjustment of the dry weight was necessary to maintain blood pressure in the normal range. Heparin requirements increased in the majority of patients because of hollow fibre clotting but there was no evidence of decreased efficacy of dialysis. In two patients clotting of arteriovenous fistula was not obviously related to the rHu-EPO treatment.
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PMID:[Treatment of anemia in chronic hemodialysis patients with recombinant human erythropoietin: long-term results in 15 patients]. 237 41

It has been shown that the regular administration of EPO permits the correction of anemia in end stage renal failure patients. We analyzed the effect of chronic administration of EPO in 13 stable, regularly-dialysed end stage renal failure patients over an 18 month period. The effects of EPO were evaluated according to standard criteria including clinical status, blood pressure control, hematology and biochemistry data, protein nutritional status and dialysis efficiency. Following a 2 week control period, EPO was administered intravenously after the dialysis session according to a 2 phase protocol. The first period (correction phase) consisted of a stepwise EPO dose increment, starting at 24 IU/kg x 3 times and doubling the dose every 14 days according to hemoglobin response in order to achieve a target hemoglobin level of 11 g/dl. In the second period (maintenance phase) EPO dose was optimized to maintain the hemoglobin level between 10 and 11 g/dl, by adjusting either the dose or the frequency of injection. Anemia was corrected in all patients within 10 weeks with EPO dose increasing from 72 to 360 IU/kg/week. The stabilisation of hemoglobin was achieved with an average EPO dose of 275 IU/kg/week (50 to 476 IU/kg/week). Concomitantly, a subjective and clinical improvement was noted in all patients. The dialysis efficacy, although remaining in an acceptable range, fell significantly by 10% over the first 3 months of treatment, remaining stable afterwards, yielding an effective urea clearance near to 120 1/week. The dietary protein intake calculated from urea kinetic modelling ranged between 1.1 and 1.2 g/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Recombinant human erythropoietin: 18 months of continuous use in substitution hemodialysis]. 237 43

In children with renal anemia the concentration of DPG of red blood cells and the O2-affinity of hemoglobin (P50) were determined before and under treatment with EPO. Before treatment the concentration of DPG was 6.25 mmoles/l cells and the P50 28.9 Torr. A rise of the hematocrit to about 0.30 was accompanied by an increase of DPG to 7.95 mmoles/l cells and of P50 to 32.1 Torr, respectively. Thus improvement of renal anemia by stimulation of erythropoiesis by means of EPO was accompanied by a decreased O2-affinity of hemoglobin and therefore by an additionally improved O2-supply to the tissues.
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PMID:Influence of erythropoietin treatment on 2,3-bisphosphoglycerate and O2-affinity of red blood cells in children with renal anemia. 238 18

The anemia associated with end-stage renal disease (ESRD) is primarily due to a deficiency in renal-derived erythropoietin. Through advances in genetic engineering, the gene for erythropoietin has been isolated and cloned, and recombinant human erythropoietin (r-HuEPO; EPOGEN, AMGEN Inc, Thousand Oaks, CA) is now available for clinical use. Study results indicate that r-HuEPO is highly effective in ameliorating symptomatic anemia in patients with chronic renal failure. Sustained dose-dependent increases in hematocrit values are achieved in at least 97% of patients, with improvement in quality of life, exercise tolerance, decrease in total body iron stores, and virtual elimination (40-fold reduction) of transfusion requirements. Hypertension is the most common side effect, but is easily controlled. To date, anti-erythropoietin antibodies have not been detected in patients treated with this product. Doses between 100 and 150 U/kg body weight are sufficient to increase hematocrit levels to normal in 2 months or less, with iron replacement therapy needed in most patients. The correction of anemia in ESRD patients promotes an increase in appetite, causing ingestion of more protein, potassium, and sodium. The resulting need for increased dialysis may burden existing dialysis facilities. Experience with 36 patients receiving r-Hu-EPO demonstrates that high-flux short-time hemodialysis is as effective as conventional hemodialysis. There were no significant differences between the groups in laboratory parameters including blood urea nitrogen, creatinine, potassium, phosphate, mean arterial pressure, and weight loss, although hematocrit values were slightly higher in the high-flux dialysis patients. Adverse effects resulting from r-HuEPO treatment were minor and were not more common in the group receiving high-flux short-time hemodialysis.
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PMID:Clinical efficacy of recombinant human erythropoietin in hemodialysis patients. 264 16


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