Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant erythropoietin (r-EPO) was administered to 37 patients with advanced, transfusion-dependent and chemo-resistant multiple myeloma (MM), at the fixed dose of 10,000/U s.c., 3 times a week, for 2 months. Thirteen patients (35.1%) achieved a significant response in terms of complete abolition of red cell transfusions. Factors significantly predictive of response were: a) inappropriate production of endogenous EPO, as expressed by a reduced observed/predicted ratio; b) presence of a consistent number of circulating erythroid precursors BFU-E; c) low serum levels of tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with inhibitory activity on erythropoiesis; d) a single line of previously received chemotherapy. Renal failure, bone marrow plasma cell infiltration, serum levels of IL-6 and other main clinical and laboratory parameters did not affect significantly the response to r-EPO. High fluorescence reticulocytes (HFR) and soluble transferrin receptor (sTfR) values were useful to detect an early stimulation of erythropoiesis in responders, while a high percentage of circulating hypochromic erythrocytes (HE), as assessed by an automated counter, identified those patients developing functional iron deficiency during r-EPO treatment. We conclude that about one-third of severely anemic patients with advanced MM, unresponsive to chemotherapy, may benefit by r-EPO therapy. The clinical management of these patients can be accomplished using non-invasive parameters, such as sTfR, HFR and HE.
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PMID:Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis. 922 86

Much progress has been made in recent years in the management of anemia associated with chronic and renal failure with recombinant human erythropoietin (r-Hu EPO). However, there remains much debate surrounding the diagnosis and treatment of iron deficiency. To ensure that full benefit from erythropoietin therapy is received, most patients require iron supplement during treatment. There are, however, few guidelines for the use of iron therapy. Iron deficiency results in an inadequate response to r-Hu EPO and is the main cause of resistance to this treatment. Oral iron therapy is of limited value in patients receiving r-Hu EPO. Thus, intravenous iron supplementation should be administered only in patients who do not tolerate available intravenous iron preparations or who are on continuous ambulatory peritoneal dialysis with no evidence of functional iron deficiency. This article provides guidelines for the diagnosis of absolute or functional iron deficiency in patients with renal anemia and suggests treatment schedules for intravenous iron supplementation. We hope that all dialysis patients will be able on this basis to achieve a satisfactory iron status and benefit fully from r-Hu EPO therapy.
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PMID:Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin-treated patients. 924 71

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.
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PMID:Safety aspects of parenteral iron in patients with end-stage renal disease. 935 60

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.
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PMID:Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO). 949 Dec 86

Recombinant human erythropoietin is used in clinical practice mainly for treatment of anemia of renal failure. In the past years, however, its use has been approved for other indications, including prevention of anemia in surgical patients or in patients undergoing platinum-based chemotherapy, treatment of anemia of prematurity, of anemia induced by zidovudine therapy in HIV-infected patients, and of anemia induced by chemotherapy of nonmyeloid malignancies. Erythropoietin should routinely be given subcutaneously to maximize its effects. Most patients undergoing rHuEpo treatment develop functional iron deficiency, a situation in which iron supply to the erythroid marrow is inadequate for the erythrocyte precursor demand. Iron supplementation should, therefore, be given to all individuals receiving rHuEpo except for those patients with increased serum iron and transferrin saturation. Outside the setting of uremia, only a portion of patients can clearly benefit from erythropoietin therapy; therefore, the use of rHuEpo should be individualized in nonrenal applications.
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PMID:How and when to use erythropoietin. 957 Jul 2

A 17 year old male suffered from iron deficiency of undetermined cause for 2 years. Iron substitution was able to correct it for short periods. With the exception of fatigue and recurring abdominal pain attributed to oral iron therapy no further symptoms were present. The physical status on admission was unremarkable. The laboratory detected intestinal disorders, an anemia of the chronic type without evidence for malignancy or renal failure suggested an inflammatory gastro-intestinal disorder. In spite of a twice negative noninvasive test for gluten-intolerance the clinician favored in his differential diagnosis non tropical sprue over inflammatory bowel disease (IBD, Crohn's disease, Whipple's disease). Histopathology of small bowel specimens did not indicate sprue. An ileo-colonoscopy revealed severe ulcerating ileitis and mild chronic colitis. The histologic specimen revealed a severe ileal inflammation with cosinophilia and the colon specimens epitheloid microgranuloma. These findings are highly compatible with the diagnosis of Crohn's disease. Iron deficiency anemia is common in Crohn's disease. In the current case it is due to disturbed iron uptake. Iron deficiency anemia as sole symptom of Crohn's disease is extremely rare.
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PMID:[Severe chronic iron deficiency in a 17-year-old student]. 962 33

The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.
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PMID:Acute-phase inflammatory process contributes to malnutrition, anemia, and possibly other abnormalities in dialysis patients. 989 76

The anemia of renal failure is caused by the lack of sufficient quantities of endogenous erythropoietin. With the availability of recombinant human erythropoietin (rHuEPO), however, it has become apparent that to achieve a given target, hematocrit requires proper management of iron replacement, as well as the administration of rHuEPO. Iron deficiency, either absolute or functional, will occur in most, if not all, patients on hemodialysis receiving rHuEPO because of the increased demand for iron driven by the accelerated erythropoiesis that occurs with exogenous rHuEPO administration, coupled with ongoing blood losses from dialyzer and tubing, blood sampling, gastrointestinal blood loss, and blood losses at the time of dialysis needle placement and removal. Blood loss is less of a problem in patients on peritoneal dialysis, but poor iron intake and increased demand for iron are also seen, the latter in patients receiving rHuEPO. It is essential, therefore, for renal health professionals to understand iron metabolism in dialysis patients in order to properly balance the therapy of renal anemia with rHuEPO and supplemental iron.
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PMID:Iron deficiency in patients with renal failure. 1008 82

In iron deficiency and lead poisoning, the enzyme ferrochelatase catalyzes the incorporation of zinc, instead of iron, into protoporphyrin IX, resulting in the formation of zinc protoporphyrin (ZPP). In healthy blood donors, there is a good inverse correlation between serum ferritin and ZPP levels. In renal failure patients and in patients with anemia caused by a variety of chronic disorders, two different types of iron deficiency are found: (a) absolute iron deficiency and (b) relative, or functional, iron deficiency. The latter occurs when iron, despite adequate stores, is not delivered rapidly enough to the erythroblasts. ZPP is not only indicative of absolute iron deficiency, but it is also, for now, the best indicator of iron-deficient erythropoiesis, along with the percentage of hypochromic red blood cells. By contrast, serum ferritin and transferrin saturation may not adequately assess functional iron deficiency. Elevated ZPP levels in renal failure patients can be caused by different pathogenetic mechanisms, such as chronic inflammatory disease, lead poisoning, and the presence of uremic factors, all of which could potentially inhibit heme biosynthesis. However, ZPP levels do not consistently predict an erythropoietic response to iron supplementation in maintenance hemodialysis patients, and thus, iron overload during i.v. iron supplementation cannot be detected by measuring ZPP.
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PMID:Erythrocyte zinc protoporphyrin. 1008 87

The effect of recombinant human erythropoietin (rHuEpo) on megakaryopoiesis remains controversial. Treatment with rHuEpo in renal failure patients has been associated with a slight elevation of platelet counts. In animal studies, high doses of rHuEpo produced an increase of platelet counts followed by a gradual return to normal after 7 to 15 days or even a substantial degree of thrombocytopenia. However, because iron deficiency is also known to be associated with thrombocytosis, (functional) iron deficiency during rHuEpo could be contributing to these observations. We investigated the impact of iron supply on changes in platelet counts induced by rHuEpo. Rats were either fed normal food (normal rats) or received 1% carbonyl iron for 2 weeks or 3 months, as well as during the experiment, to achieve iron supplementation or overload, respectively. Rats of all three categories then received daily intravenous injections of rHuEpo (10, 50, or 150 U) or normal saline (0 U) for 20 days. With 0 to 10 U rHuEpo, platelets remained stable. In normal rats receiving 50 to 150 U rHuEpo, platelets increased to 120% to 140% of baseline at 4 to 12 days to level off at 120% at 16 to 20 days. This response was less sustained in splenectomized animals. Iron-supplemented rats receiving 50 to 150 U rHuEpo also increased platelets initially, but the peak was at day 4, followed by a gradual return to baseline and even a moderate thrombocytopenia later on. Iron-overloaded rats receiving 50 to 150 U rHuEpo also had increased platelets at day 4, but the duration of platelet increase was shorter, and they experienced a more pronounced degree of thrombocytopenia in proportion to the dose of rHuEpo. Because the early elevation of platelets was of larger magnitude than hematocrit changes, it is unlikely that it could be accounted for by shrinkage of plasma volume. Because it was observed in all three iron conditions, there appears to be some direct positive effect of rHuEpo on platelet production. However, after this transient effect, expanded erythropoiesis appears to exert a negative impact upon platelet production. Secondary thrombocytopenia was not related to splenic pooling, and its very slow correction after cessation of rHuEpo therapy is not compatible with changes in platelet survival. Rather, it is consistent with stem cell competition between erythroid and megakaryocytic development. However, this secondary thrombocytopenia is masked by (functional) iron deficiency in rats not receiving an adequate iron supply from food or stores.
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PMID:The effect of recombinant human erythropoietin on platelet counts is strongly modulated by the adequacy of iron supply. 1023 80


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