Detection of functional iron deficiency during erythropoietin treatment: a new approach.

Macdougall, Iain C.; Cavill, I.; Hulme, B.; Bain, Barbara J.; McGregor, E.; McKay, Pamela; Sanders, Elizabeth A.; Coles, Gerald A.; Williams, J. D.

doi:10.1136/bmj.304.6821.225

Cited by 228 publications

(117 citation statements)

References 6 publications

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“…The initial experience with patients on chronic dialysis (9 ) and subsequent studies of healthy individuals (10,11 ) have shown that, despite the use of oral iron supplements, the increased erythropoietic activity induced by r-HuEPO cannot be sustained by the normally available iron, and iron-deficient erythropoiesis develops. A course of r-HuEPO therapy induces a reduction in serum iron and desaturation of transferrin to values below the threshold of 16% saturation, which is associated with iron-deficient erythropoiesis.…”

Section: R-huepo Therapy and Functional Iron Deficiencymentioning

confidence: 99%

“…Thus, additional laboratory markers need to be used to assess the balance between erythropoiesis and available iron. has been shown to identify the development of iron deficiency in dialysis patients and of functional iron deficiency in healthy individuals treated with r-HuEPO (9,10 ). Technical limitations of this marker are related to its sensitivity to temperature and storage (over time, red cells swell, MCHC decreases, and %HYPO increases) and to the inaccurate determination of MCHC by electrical impedance instruments in samples with hypochromic erythrocytes (12 ).…”

Section: R-huepo Therapy and Functional Iron Deficiencymentioning

confidence: 99%

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Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

2003

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Iron deficiency anemia is one of the most common diseases worldwide. In the majority of cases, the presence of hypochromic microcytic anemia and biochemical evidence for depletion of body iron stores makes the diagnosis relatively straightforward. However, in several clinical conditions, classic biochemical indices such as serum iron, transferrin saturation, and ferritin may not be informative or may not change rapidly enough to reflect transient iron-deficient states (functional iron deficiency), such as the ones that develop during recombinant human erythropoietin (r-HuEPO) therapy. The identification and treatment of iron deficiency in settings such as r-HuEPO therapy, anemia of chronic disease, and iron deficiency of early childhood may be improved by the use of red cell and reticulocyte cellular indices, which reflect in almost real time the development of iron deficiency and the response to iron therapy. In the anemia of chronic disease, measurements of plasma cytokines and iron metabolism regulators such as hepcidin (when available) may be helpful in the characterization of the pathophysiologic basis of this condition. The ratio of serum transferrin receptor (sTfR) to serum ferritin (R/F ratio) has been shown to have excellent performance in estimating body iron stores, but it cannot be used widely because of the lack of standardization for sTfR assays. The combination of hematologic markers such as reticulocyte hemoglobin content, which decreases with iron deficiency, and R/F ratio may allow for a more precise classification of anemias.

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Section: R-huepo Therapy and Functional Iron Deficiencymentioning

confidence: 99%

Section: R-huepo Therapy and Functional Iron Deficiencymentioning

confidence: 99%

Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

2003

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“…Adequate iron supply, which is achieved mainly by administration of parenteral iron, is a prerequesite for successful stimulation of erythropoiesis with rhEPO [22][23][24]. We have already reported on several studies using rhEPO in combination with oral iron for the treatment of postpartum anaemia [25,27,36].…”

Section: Introductionmentioning

confidence: 99%

Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia

Breymann

Zimmermann

Huch

et al. 1996

Eur J Clin Investigation

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Abstract. The authors compared the effect of recombinant human erythropoietin (rhEPO) in combination with iron with that of iron therapy only in the treatment of postpartum anaemia. Ninety patients (30 patients/ group) received either rhEPO (300 U kg ÿ 1 , i.v. or s.c., once) and iron (parenteral and oral), or iron therapy only. Erythropoiesis was assessed by haemoglobin and haematocrit increase, absolute reticulocyte counting and reticulocyte flow cytometry. Ferrokinetics was assessed by serum ferritin, transferrin and transferrin saturation measurements. There was no difference before therapy for baseline haematological values or iron status. Patients with endogenous EPO levels below 145 mU mL ÿ 1 had a significant benefit from intravenous rhEPO administration with highest haematocrit and haemoglobin levels 4 and 14 days after therapy. rhEPO-treated groups showed a higher absolute reticulocyte count 1 and 4 days after therapy and an elevated percentage of high fluorescent reticulocytes (HFRs). Parenteral iron therapy caused a significant increase of ferritin and transferrin saturation, while transferrin concentration decreased. Ferritin and transferrin levels were lowest after i.v. administration of rhEPO, 1 and 4 days after therapy. C-reactive protein concentration was highest in patients who underwent caesarean section until the end of the observation period. A single dose of rhEPO in combination with iron was more effective in treating postpartum anaemia than iron therapy only, in patients who had low EPO levels despite peripartal blood loss. Postpartum low endogenous EPO levels might be a consequence of inhibiting inflammatory cytokines that are released after spontaneous or operative deliveries.

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“…The increase in the target hematocrit was supported by a structured review of available clinical literature that gave rise to clinical practice guidelines advocating a hematocrit range from 33 to 36% (4). Because absolute or relative iron deficiency, arising from exhaustion of marrow iron stores and/or the inability to deliver adequate iron stores to support normoblast proliferation and maturation (5)(6)(7)(8)(9)(10), are common causes of inefficiency in EPO response, concomitant clinical practice guideline statements have been developed for iron administration (4).…”

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confidence: 99%

Trends in Anemia Management among US Hemodialysis Patients

Coladonato¹,

Frankenfield²,

Reddan³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 Ϯ 5.2% to 34.1 Ϯ 3.7% and from 58.2 Ϯ 41.8 U/kg to 68.2 Ϯ 55.0 U/kg, respectively (P ϭ 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P ϭ 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P Ͻ 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P ϭ 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.

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Detection of functional iron deficiency during erythropoietin treatment: a new approach.

Cited by 228 publications

References 6 publications

Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia

Trends in Anemia Management among US Hemodialysis Patients

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