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

Over the past decade experimental haematologists have identified and eventually characterised a number of polypeptide growth factors capable of stimulating the proliferation and differentiation of haemopoietic progenitor cells in vitro. The molecular cloning of these growth factors has now allowed their use in vivo, and some of them have shown promise in recent clinical trials. Most of the work has been done on erythropoietin and myeloid growth factors, which are discussed in this review. Erythropoietin has been used successfully as replacement therapy in the anaemia of end-stage renal failure, but may also prove clinically useful in other chronic anaemias and, in combination with other growth factors, as a stimulant of bone marrow regeneration following bone marrow transplant. Myeloid growth factors, and, in particular, granulocyte colony-stimulating factor, have been shown to accelerate neutrophil recover in cancer patients following chemotherapy, with a reduction in the number of severe infections and mucositis.
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PMID:Clinical use of haematopoietic growth factors. 265 Jul 78

Clinical trials have clearly demonstrated the efficacy of recombinant human erythropoietin (r-HuEPO) (EPOGEN [epoetin alfa]; AMGEN Inc, Thousand Oaks, CA) in the treatment of the anemia associated with end-stage renal disease (ESRD). Nearly all dialysis patients treated with r-HuEPO have responded by reaching target hematocrit levels within 8 to 12 weeks. Maintenance therapy has been effective, and some patients have had stable blood counts for greater than 2 years. The drug has been well tolerated, has resulted in elimination of transfusion dependency, and has evoked no antibody formation. Significant management issues include maintenance of sufficient iron stores to sustain red cell production and the control of blood pressure (BP) elevation associated with increased peripheral vascular resistance resulting from rising hematocrit (HCT) levels. Preliminary results of quality-of-life assessments confirm the beneficial effects of r-HuEPO therapy. This drug should become standard therapy for patients with the anemia of ESRD.
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PMID:The promise of recombinant human erythropoietin. 265 1

The effect of long-term hemodialysis in 58 nonanemic end-stage renal disease patients treated with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) has been examined in detail. Increased dialyzer prescription (Kt/V) was correlated with the need for a lower maintenance dose of r-HuEPO. After 1 year of therapy, stable increases in hemoglobin, hematocrit, and reticulocyte levels were obtained without other clinically significant hematologic changes. In a randomly selected subgroup of 14 patients, 5 developed predialysis increased diastolic pressures. In this group, an early increase in cardiac output and ejection fraction was accompanied by a decrease in total peripheral resistance index (TPRI). Later changes showed a steady increase in TPRI with an associated mild increase in mean arterial pressure. A slight increase in cardiac responsiveness to fistula occlusive maneuvers was also found. Hospital admissions and mortality rates were not significantly different from those of a cohort control population. At a fixed Kt/V there were slight decreases in solute clearances with correction of anemia, with phosphate, urate, and creatinine changing significantly. Corrective measures required simple compensatory adjustments in dialysis blood-flow rates. Intradialytic complications were noticeably improved. Patients receiving long-term r-HuEPO replacement therapy do remarkably well without major complications.
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PMID:Practical considerations of recombinant human erythropoietin therapy. 266 48

Extensive testing has proven that recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) corrects the anemia of end-stage renal disease and eliminates the need for transfusions in virtually all patients. Patients whose hematocrit levels are less than 0.30 or who are transfusion dependent are candidates for therapy. A dosage of 50 to 150 U/kg body weight intravenously three times a week produces an increase in hematocrit by approximately 0.01 to 0.02 per week. Once the hematocrit reaches 0.30 the dose is adjusted so that a target hematocrit of 0.32 to 0.38 is maintained. Eighty percent of patients need maintenance doses of r-HuEPO of less than or equal to 150 U/kg; the other 20% of patients require larger doses. Reasons for poor responses include iron deficiency, inflammation due to surgery or infection, and osteitis fibrosa. Most patients require iron supplementation to prevent functional iron deficiency. BP increased in one third of patients, and in 3% seizures occurred during the initial phase of therapy, often associated with a sudden increase in BP. This hypertension can be controlled with medication. Increased dialyzer clotting may occur, which is prevented when heparin doses are adjusted, and dialyzer solute clearances may decrease slightly. Treatment with r-HuEPO does not elicit an antibody response. The mechanism of action of r-HuEPO is identical to that of natural erythropoietin, and therefore is an appropriate therapy for the long-term management of anemia in chronic renal failure.
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PMID:Guidelines for recombinant human erythropoietin therapy. 266 49

Effective monitoring of chronic hemodialysis patients treated with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) includes an initial evaluation of the patient, the patient's anemia, and the patient's iron stores. Assessment of iron stores includes obtaining hematocrit and hemoglobin levels, reticulocyte count, red cell indices, serum ferritin level, transferrin percent saturation, and the patient's transfusion history. If iron stores are inadequate to support the increased erythropoiesis induced by the therapy, appropriate iron replacement therapy should be provided. Monitoring also involves assessment of BP (and its control), because development or exacerbation of hypertension is the most significant side effect associated with this treatment. Because the dose-response relationship for r-HuEPO therapy has been clearly documented, a target hematocrit and target rate of increase in hematocrit can be established. As anemia improves, continued monitoring of hematocrit, hemoglobin, red cell indices, serum ferritin level, and transferrin percent saturation will ensure that depleted iron stores are noted and treated as necessary. Heparin requirements during dialysis, blood chemistries, and blood access problems should also be monitored. No data currently exist suggesting that dialyzer reuse is compromised by r-HuEPO therapy. Quality-of-life surveys show improvement with r-HuEPO treatment and effective reduction of anemia. There is also some indication that morbidity is lessened and survival improved when anemia is treated with r-HuEPO therapy.
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PMID:Monitoring considerations in recombinant human erythropoietin therapy. 266 80

Onset or exacerbation of hypertension has been observed as a possible complication of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for the anemia of end-stage renal disease. This effect is attributed to an overly rapid rise in the hematocrit level and the accompanying consequences, which include increased hemoglobin, blood viscosity, and red cell mass, as well as normalization of the cardiac index of anemia. The sluggish response to these changes by compensatory mechanisms, resulting in increased peripheral vascular resistance, may be the means by which BP becomes elevated during therapy. Although more than one third of patients receiving r-HuEPO therapy have developed sustained increases in diastolic pressure of 10 mmHg or more, this potential problem is controllable. Prevention or correction of hypertension is accomplished by initiating therapy with a low-dose regimen that is slowly increased, thereby preventing a rapid rise in the hematocrit level. Drug intervention, together with dialysis prescription modification and restriction of dietary salt and fluid to regulate weight, can effectively control BP. Discontinuation of therapy for severe and uncontrollable hypertension rarely becomes necessary.
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PMID:Management of blood pressure changes during recombinant human erythropoietin therapy. 266 81

Iron deficiency frequently complicates both acute and chronic phases of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for dialysis-associated anemia. During acute correction of anemia, iron needed for new hemoglobin production may outstrip available body iron stores. During maintenance r-HuEPO therapy, blood lost both through the dialysis process and the uremic predisposition to gastrointestinal bleeding promotes ongoing negative iron balance. Failure to recognize and treat iron deficiency may lead to impaired efficacy of r-HuEPO in the anemic patient by converting the anemia associated with chronic renal failure to the anemia associated with iron deficiency. The risk of iron deficiency is assessed by weighing available iron stores, as reflected by the level of serum ferritin, against anticipated iron needs for new hemoglobin synthesis, as measured by the difference between the current and target hemoglobin. Using this approach, body iron reserves can be determined, iron deficits predicted, and appropriate iron replacement therapy planned. Once patients are identified as being at risk for iron deficiency, they are treated prophylactically with oral iron supplements. Parenteral iron therapy is reserved for those at greatest risk for iron deficiency during acute r-HuEPO treatment and those intolerant or unresponsive to oral iron supplements during chronic r-HuEPO treatment. Although no dose-response relationship has been observed in the restoration of iron balance with oral iron supplements, those taking supplements show distinctly higher projected iron stores and daily iron balance than those not given supplements.
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PMID:Iron deficiency in patients with dialysis-associated anemia during erythropoietin replacement therapy: strategies for assessment and management. 266 82

The clinical manifestations of uremia are only incompletely reversed by chronic hemodialysis. Signs and symptoms can include abnormalities in electrophysiologic indices, clinical mental status, and neuropsychological test performance, as well as decreases in exercise tolerance, sexual potency, and general quality of life. Though retention of uremic toxins is responsible for many of these symptom complexes, some may be caused, or substantially aggravated, by the anemia that almost invariably accompanies chronic renal failure. Treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) increases hematocrit values and thus reduces the anemia, in turn improving brain and cognitive function, exercise tolerance, sexual potency, and quality of life.
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PMID:Recombinant human erythropoietin: impact on brain and cognitive function, exercise tolerance, sexual potency, and quality of life. 266 83

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.
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PMID:Who should receive recombinant human erythropoietin? 266 84

Recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) has proven to be an effective agent in treating the anemia of chronic renal failure. Of patients enrolled in recent phase III trials in the United States, 97% have responded with near normalization of hematocrit within 12 weeks of therapy. Small numbers of patients, however, may exhibit sluggish or minimal responsiveness to treatment. In these patients, loss of responsiveness due to red cell substrate depletion (in particular, iron deficiency) or underlying inflammatory disease may occur at any time during the treatment calendar, whether at induction of therapy or during maintenance treatment. Primary unresponsiveness at initiation of treatment may also result from such potentially reversible abnormalities as aluminum intoxication, poorly controlled hyperparathyroidism, and, possibly, severe azotemia. These abnormalities can be investigated in a systemic fashion and frequently corrected so that successful treatment can resume.
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PMID:Resistance to recombinant human erythropoietin therapy: a real clinical entity? 266 85


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