losartan-potassium and Anemia--Iron-Deficiency

Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.. The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.. We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.. Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.. Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.. We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all o. Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Humans; Renal Insufficiency, Chronic; Risk Factors

Preoperative anemia affects 30-40% of patients undergoing major surgery and is an independent risk factor for perioperative blood transfusion, morbidity, and mortality. Absolute or functional iron deficiency is its leading cause. Nonanemic hematinic deficiencies are also prevalent and may hamper preoperative hemoglobin optimization and/or recovery from postoperative anemia. As modifiable risk factors, anemia and hematinic deficiencies should be detected and corrected prior to major surgical procedures. Postoperative anemia is even more common (up to 80-90%) due to surgery-associated blood loss, inflammation-induced blunted erythropoiesis, and/or preexisting anemia. Preoperative oral iron may have a role in mild-to-moderate anemia, provided there is sufficient time (6-8 weeks) and adequate tolerance of oral preparations. Postoperative oral iron is of little value and rife with gastrointestinal adverse events. Intravenous iron should preferentially be used in cases of moderate-to-severe iron deficiency anemia, concomitant use of erythropoiesis-stimulating agents, short time to surgery or nonelective procedures, and for postoperative anemia management. Minor infusion reactions to intravenous iron are rare, the incidence of severe anaphylactic reactions is extremely low, and there is no increase in infections with intravenous iron. Currently available intravenous iron formulations allowing administration of large single doses are preferred.

Topics: Anemia, Iron-Deficiency; Arthroplasty, Replacement; Erythrocyte Transfusion; Erythropoietin; Gastrointestinal Diseases; Humans; Iron; Perioperative Care

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics.

Topics: Anemia; Anemia, Iron-Deficiency; Anti-Bacterial Agents; Antiviral Agents; Blood Transfusion; Erythropoietin; Graft Rejection; Hematinics; Hemolysis; Humans; Immunosuppressive Agents; Infections; Iron Compounds; Kidney Failure, Chronic; Kidney Transplantation; Neoplasms; Sex Factors; Time Factors

Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system.

Topics: Anemia, Iron-Deficiency; Animals; Cell Differentiation; Disease Models, Animal; Embryonic Development; Epigenesis, Genetic; Erythropoiesis; Erythropoietin; Female; Granulocytes; Hematopoiesis; Humans; Leukemia, Promyelocytic, Acute; Pregnancy; Receptors, Retinoic Acid; Signal Transduction; Tretinoin; Vitamin A; Vitamin A Deficiency

Anemia is a common complication in patients with chronic kidney disease (CKD), mainly due to inadequate renal production of erythropoietin. In hemodialysis (HD) patients this condition may be aggravated by iron deficiency (absolute or functional). The correction of this anemia is usually achieved by treatment with erythropoiesis stimulating agents (ESAs) and iron (oral or intravenous). Studies questioning the safety of ESAs (especially at higher doses) changed the pattern of anemia treatment in CKD patients. According to the new guidelines, when transferrin saturation is lower than 30% and ferritin lower than 500 ng/mL, a trial with iron should be started, to avoid therapy with ESAs or at least to reduce the doses needed to treat the anemia. Recent reports showed increasing ferritin levels, towards values above 800 ng/mL, in CKD patients treated according to the guidelines. In this review we focus on the risks of the increased iron use to treat CKD anemia, namely, iron overload and toxicity, increased risk of infections, as well as mortality.

Topics: Anemia, Iron-Deficiency; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Ferritins; Hematinics; Humans; Iron; Iron Overload; Kidney; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Survival Analysis; Transferrin

The management of anemia in patients with chronic kidney disease (CKD) is difficult. The availability of erythropoiesis-stimulating agents (ESAs) has increased treatment options for previously transfusion-requiring patients, but the recent evidence of ESA side effects has prompted the search for complementary or alternative approaches. Next to ESA, parenteral iron supplementation is the second main form of anemia treatment. However, as of now, no systematic approach has been proposed to balance the concurrent administration of both agents according to individual patient's needs. Furthermore, the potential risks of excessive iron dosing remain a topic of controversy. How, when and whether to monitor CKD patients for potential iron overload remain to be elucidated. This review addresses the question of risk and benefit of iron administration in CKD, highlights the evidence supporting current practice, provides an overview of standard and potential new markers of iron status and outlines a new pharmacometric approach to physiologically compatible individualized dosing of ESA and iron in CKD patients.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Hematinics; Humans; Iron Compounds; Iron Overload; Renal Insufficiency, Chronic

The management of anaemia in patients with chronic kidney disease has been transformed by development of erythropoiesis-stimulating agents (ESAs). Following expiry of the patent of the originator epoetin alfa in Europe, a number of biosimilar ESAs have been licensed for use in the nephrology setting. Biosimilars are biological medicines that are approved via stringently defined regulatory pathways on the basis that they have demonstrated comparable safety, efficacy and quality to their reference product.. As nurses have a pivotal role in patient care, not only administering medications but also educating patients about their treatment options, it is important that nurses understand the differences between biosimilar medicines and their reference products and appreciate the stringent regulatory requirements for approval of biosimilars.. In this review, we use epoetin zeta as a case study to highlight practical considerations of using biosimilar ESAs in the management of patients with kidney disease.. Biosimilar products, such as epoetin zeta, may offer a range of features to patients, nurses and physicians, such as greater flexibility over dose and route of administration, in addition to greater access to biological medicines through cost savings.. Renal nurses play a significant role in the management of patients with kidney disease and anaemia, not only having an important role in the delivery of medicine but also in the education of patients. This review discusses some of the practical aspects associated with the use of biosimilar medicines to assist nurses in making informed decisions over their use.

Topics: Anemia, Iron-Deficiency; Biosimilar Pharmaceuticals; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins

Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.

Topics: Anemia, Iron-Deficiency; Animals; Cross-Sectional Studies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Ferritins; Hematinics; Humans; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Prognosis; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Assessment; Treatment Outcome

Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF patients). Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Heart Failure; Humans

Postpartum iron deficiency anaemia is caused by bleeding or inadequate dietary iron intake/uptake. This condition is defined by iron deficiency accompanied by a lower than normal blood haemoglobin concentration, although this can be affected by factors other than anaemia and must be interpreted in the light of any concurrent symptoms. Symptoms include fatigue, breathlessness, and dizziness. Treatment options include oral or intravenous iron, erythropoietin which stimulates red blood cell production, and substitution by red blood cell transfusion.. To assess the efficacy and harms of the available treatment modalities for women with postpartum iron deficiency anaemia.. The Cochrane Pregnancy and Childbirth Group's Trials Register (9 April 2015); the WHO International Clinical Trials Registry Portal (ICTRP), and the Latin-American and Caribbean Health Sciences Literature database (LILACS) (8 April 2015) and reference lists of retrieved studies.. We included published, unpublished and ongoing randomised controlled trials that compared a treatment for postpartum iron deficiency anaemia with placebo, no treatment, or another treatment for postpartum iron deficiency anaemia, including trials described in abstracts only. Cluster-randomised trials were eligible for inclusion. We included both open-label trials and blinded trials, regardless of who was blinded. The participants were women with a postpartum haemoglobin of 120 g per litre (g/L) or less, for which treatment was initiated within six weeks after childbirth.Non-randomised trials, quasi-randomised trials and trials using a cross-over design were excluded.. Two review authors independently assessed studies for inclusion, quality, and extracted data. We contacted study authors and pharmaceutical companies for additional information.. We included 22 randomised controlled trials (2858 women), most of which had high risk of bias in several domains. We performed 13 comparisons. Many comparisons are based on a small number of studies with small sample sizes. No analysis of our primary outcomes contained more than two studies.Intravenous iron was compared to oral iron in 10 studies (1553 women). Fatigue was reported in two studies and improved significantly favouring the intravenously treated group in one of the studies. Other anaemia symptoms were not reported. One woman died from cardiomyopathy (risk ratio (RR) 2.95; 95% confidence interval (CI) 0.12 to 71.96; two studies; one event; 374 women; low quality evidence). One woman developed arrhythmia. Both cardiac complications occurred in the intravenously treated group. Allergic reactions occurred in three women treated with intravenous iron, not statistically significant (average RR 2.78; 95% CI 0.31 to 24.92; eight studies; 1454 women; I² = 0%; low quality evidence). Gastrointestinal events were less frequent in the intravenously treated group (average RR 0.31; 95% CI 0.20 to 0.47; eight studies; 169 events; 1307 women; I² = 0%; very low quality evidence).One study evaluated red blood cell transfusion versus non-intervention. General fatigue improved significantly more in the transfusion group at three days (MD -0.80; 95% CI -1.53 to -0.07; women 388; low quality evidence), but no difference between groups was seen at six weeks. Maternal mortality was not reported.The remaining comparisons evaluated oral iron (with or without other food substances) versus placebo (three studies), intravenous iron with oral iron versus oral iron (two studies) and erythropoietin (alone or combined with iron) versus placebo or iron (seven studies). These studies did not investigate fatigue. Maternal mortality was rarely reported.. The body of evidence did not allow us to reach a clear conclusion regarding the efficacy of the interventions on postpartum iron deficiency anaemia. The quality of evidence was low.Clinical outcomes were rarely reported. Laboratory values may not be reliable indicators for efficacy, as they do not always correlate with clinical treatment effects. It remains unclear which treatment modality is most effective in alleviating symptoms of postpartum anaemia.Intravenous iron was superior regarding gastrointestinal harms, however anaphylaxis and cardiac events occurred and more data are needed to establish whether this was caused by intravenous iron.The clinical significance of some temporarily improved fatigue scores in women treated with blood transfusion is uncertain and this modest effect should be balanced against known risks, e.g. maternal mortality (not reported) and maternal immunological sensitisation, which can potentially harm future pregnancies.When comparing oral iron to placebo it remains unknown whether efficacy (relief of anaemia symptoms) outweighs the documented gastrointestinal harms.We could not draw conclusions regarding erythropoietin treatment due to lack of evidence.Further research should evaluate treatment effect through clinical outcomes, i.e. presence and severity of anaemia symptoms balanced against harms, i.e. survival and severe morbidity.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Humans; Injections, Intravenous; Iron; Postpartum Period; Puerperal Disorders; Randomized Controlled Trials as Topic

Postoperative nosocomial infection (PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions (ABTs), anemia, and iron deficiency are manageable with perioperative intravenous (IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI.. Pooled data on ABT, PNI, 30-day mortality, and length of hospital stay (LHS) from 2547 patients undergoing elective lower-limb arthroplasty (n = 1186) or hip fracture repair (n = 1361) were compared between patients who received either very-short-term perioperative IV iron (200-600 mg; n = 1538), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU), or standard treatment (n = 1009).. Compared to standard therapy, perioperative IV iron reduced rates of ABT (32.4% vs. 48.8%; p = 0.001), PNI (10.7% vs. 26.9%; p = 0.001), and 30-day mortality (4.8% vs. 9.4%; p = 0.003) and the LHS (11.9 days vs. 13.4 days; p = 0.001) in hip fracture patients. These benefits were observed in both transfused and nontransfused patients. Also in elective arthroplasty, IV iron reduced ABT rates (8.9% vs. 30.1%; p = 0.001) and LHS (8.4 days vs.10.7 days; p = 0.001), without differences in PNI rates (2.8% vs. 3.7%; p = 0.417), and there was no 30-day mortality.. Despite known limitations of pooled observational analyses, these results suggest that very-short-term perioperative administration of IV iron, with or without rHuEPO, in major lower limb orthopedic procedures is associated with reduced ABT rates and LHS, without increasing postoperative morbidity or mortality.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Blood Transfusion; Cross Infection; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Iron; Length of Stay; Male; Middle Aged; Morbidity; Observational Studies as Topic; Orthopedic Procedures; Perioperative Period; Retrospective Studies; Risk Factors; Time Factors; Transfusion Reaction

Topics: Aged; Algorithms; Anemia; Anemia, Iron-Deficiency; Cardiovascular Diseases; Cohort Studies; Comorbidity; Darbepoetin alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Peptides; Renal Dialysis

Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

Topics: Anemia; Anemia, Iron-Deficiency; Cytokines; Dietary Supplements; Erythropoietin; Ferritins; Folic Acid Deficiency; Hemolysis; Hepcidins; Humans; Inflammatory Bowel Diseases; Iron; Prognosis; Quality of Life; Vitamin B 12 Deficiency

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

Topics: Algorithms; Anemia, Iron-Deficiency; Critical Care; Erythropoiesis; Erythropoietin; Female; Ferritins; Heart Diseases; Hematology; Humans; Iron; Male; Neoplasms; Pregnancy; Pregnancy Complications, Hematologic; Quality of Life; Respiration Disorders; Treatment Outcome

Anemia is a risk factor for increased postoperative morbidity and mortality. International guidelines, therefore, recommend preoperative diagnostic work up and causal treatment of anemia. Iron therapy, however, is suspected to negatively affect disease progression in patients with cancer-associated anemia. The objective of our systematic review was to assess the efficacy and safety of perioperative diagnosis and causal therapy of anemia, and to determine the effect of iron supplement on disease progression of cancer.We systematically searched multiple electronic databases. Two persons independently reviewed abstracts and full-text articles. We rated the risk of bias using the Cochrane Risk of Bias Tool and assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Meta-Analyses were performed using the DerSimonian&Laird random effects method. Results indicate that preoperative therapy of anemia could reduce the need for blood transfusions (relative risk: 0,78; 95% confidence interval 0,61-1,02; number needed to treat: 6) For other patient-relevant outcomes the number of events were too small to detect clinically relevant differences. We could not find any evidence that iron supplements have an influence on the progression of tumors.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Disease Progression; Erythropoietin; Evidence-Based Medicine; Humans; Iron Compounds; Neoplasms; Perioperative Care; Prognosis; Randomized Controlled Trials as Topic

Anemia in chronic kidney disease (CKD) may affect up to 90% of the patients. It is one of the non typical risk factors of cardiovascular disease, specific for this population. The main reasons of the anemia in CKD are iron and erythropoietin deficiency. It is recognized in women with hemoglobin concentration < 11 g/dl and in men and postmenopausal women with hemoglobin concentration < 12 g/dl. Other potentially reversible reasons of anemia should be excluded in differential diagnosis. Iron and erythropoiesis stimulating agents (ESA) constitute the main treatment of anemia of CKD.

Topics: Anemia, Iron-Deficiency; Cardiovascular Diseases; Causality; Comorbidity; Erythropoietin; Female; Hematinics; Humans; Male; Renal Insufficiency, Chronic; Risk Factors

Anemia is a frequent comorbidity of heart failure and is associated with poor outcomes. Anemia in heart failure is considered to develop due to a complex interaction of iron deficiency, kidney disease, and cytokine production, although micronutrient insufficiency and blood loss may contribute. Currently, treatment of anemia of heart failure lacks clear targets and specific therapy is not defined. Intravenous iron use has been shown to benefit anemic as well as nonanemic patients with heart failure. Treatment with erythropoietin-stimulating agents has been considered alone or in combination with iron, but robust evidence to dictate clear guidelines is not currently available. Available and emerging new agents in the treatment of anemia of heart failure will need to be tested in randomized, controlled studies.

Topics: Age Factors; Aged; Anemia; Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Female; Heart Failure; Hematinics; Humans; Incidence; Inflammation Mediators; Iron; Male; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sex Factors

Iron Deficiency Anaemia (IDA) has been shown to be the most common cause of anaemia worldwide. It is accepted that people with chronic kidney disease (CKD) develop anaemia as their kidney function declines.. To better understand IDA in CKD, it is necessary to appreciate the normal iron metabolism and utilisation of iron and how these processes can be disordered in patients with CKD. The problems related to infection / inflammation and oxidative stress are examined. Whilst National and international guidelines recommend specific tests for IDA, these and alternative tests are reviewed.. Whilst iron supplementation is necessary for CKD patients with IDA, iron metabolism and utilisation can be affected by factors such as infection or inflammation. Iron is essential element for all life, it can be toxic to cells through the process of oxidative stress. The recommended tests for IDA may be affected by factors such as infection and inflammation. Alternative tests are available, which may be a more accurate indicator of IDA as they are not affected by external factors.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Guideline Adherence; Hepcidins; Humans; Infections; Inflammation; Iron; Kidney Failure, Chronic; Oxidative Stress; Reference Values

Trials studying iron repletion in patients with chronic heart failure (CHF) and iron deficiency are underpowered to find consistent hard endpoint (mortality and hospitalization) reductions. We conducted a meta-analysis of controlled trials to examine the effects of iron repletion on these parameters.. Pubmed, CENTRAL, EMBASE and NIH Clinical Trials databases were searched for controlled trials utilizing intravenous iron, with or without erythropoietin, in patients with CHF with NYHA class ≥ II, iron deficiency, and left ventricular dysfunction. Data regarding hospitalizations, mortality, adverse events, NYHA class, and ejection fraction were extracted, analyzed for heterogeneity, and pooled using the DerSimonian and Laird random effects model. We identified 5 controlled trials (n = 631 patients). Patients treated with intravenous iron had significant reductions in hospitalizations (OR 0.26, 95% CI 0.08-0.80), adverse events (OR 0.35, 95% CI 0.21-0.60), NYHA class (mean improvement 1.2 classes, 95% CI 0.69-1.78, and LVEF (mean improvement 5.0%, 95% CI 0.13-9.80) but no relationship was found on mortality (OR 0.66, 95% CI 0.30-1.44).. Treatment of iron deficiency in patients with CHF reduces the risk of hospitalizations without increased adverse events, suggesting its role as a potential therapeutic target in this group of patients.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Erythropoietin; Heart Failure; Humans; Iron; Treatment Outcome

Anemia is common in inflammatory bowel disease (IBD), with a prevalence ranging from 8.8% to 73.7%. This wide range reflects the definitions used and the populations studied. Although many patients are reported to be asymptomatic, systematic studies have shown anemia to have a significant impact on quality of life. Consequently treatment should be instituted early. The commonest cause of anemia in IBD is iron deficiency, predominantly related to gastrointestinal blood loss. Anemia of chronic disease often occurs concomitantly, due to cytokine-mediated impaired erythropoiesis and dysregulated iron metabolism. Oral iron is a simple and effective method for treating iron deficiency, but requires long courses of treatment. It is also theoretically implicated with worsening intestinal inflammation, via the production of toxic reactive oxygen species. Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly. In patients failing to respond to intravenous iron, the anemia of chronic disease is most likely to be causative. In this setting evidence suggests that additional erythropoietin therapy can be effective. Blood transfusions should be avoided as part of routine management and reserved for patients with substantial acute gastro-intestinal bleeding, where there is a risk of hemodynamic compromise. This article discusses the underlying physiology of anemia in IBD, and presents the current evidence supporting treatment options available.

Topics: Anemia, Iron-Deficiency; Animals; Erythropoietin; Humans; Inflammatory Bowel Diseases; Iron

Chronic heart failure is a common disorder associated with unacceptably high mortality rates. Chronic renal disease and anemia are two important comorbidities that significantly influence morbidity and mortality in patients with chronic heart failure (CHF). Progress in CHF again may cause worsening of kidney function and anemia. To describe this vicious cycle, the term cardio-renal anemia syndrome has been suggested. Iron deficiency is part of the pathophysiology of anemia in both CHF and chronic kidney disease, which makes it an interesting target for treatment of anemia in cardio-renal anemia syndrome. Recently, studies have highlighted the potential clinical benefits of treating iron deficiency in patients with CHF, even if these patients are nonanemic. This article summarizes studies investigating the influence of iron deficiency with or without anemia in chronic kidney disease and CHF and gives an overview of preparations of intravenous iron currently available.

Topics: Anemia, Iron-Deficiency; Cardio-Renal Syndrome; Chronic Disease; Erythropoietin; Ferric Compounds; Hematinics; Humans; Iron

Development of cytotoxic chemotherapy, which has several side effects, has resulted in the development in supportive care as well. Two families of novel drugs have spread in the care of chemotherapy induced anaemia: human recombinant erythropoietin and intravenous iron. They were praised for the decreased transfusion demand and the increased quality of life. However, if we read the literature critically, our enthusiasm should be decreased. New data show an unfavourable impact of erythropoietin on life expectancy. Furthermore, the health care policy has changed since the introduction of erythropoietin 25 years ago. Transfusion control has improved and cost awareness in health care has increased. Recommendations of the American Societies of Haematology and Clinical Oncology reflect on these considerations. Erythropoietin is not recommended in adjuvant settings. The choice between erythropoietin and transfusion is conferred to the clinician in case of the development of metastases. No sufficient scientific argument was found to support the use of intravenous iron supplementation.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Health Policy; Hematinics; Humans; Hungary; Infusions, Intravenous; Iron Compounds; Life Expectancy; Medical Oncology; Neoplasms; Quality of Life; Recombinant Proteins

Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.

Topics: Anemia; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Erythropoiesis; Erythropoietin; Hepcidins; Homeostasis; Humans; Iron, Dietary; Models, Biological; Renal Insufficiency, Chronic

To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy.. French and English publications were searched using PubMed and Cochrane library.. Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion.. Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Dietary Supplements; Erythropoietin; Female; Humans; Injections, Intravenous; Iron; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Recombinant Proteins

Topics: Anemia; Anemia, Iron-Deficiency; Avitaminosis; Disease Management; Drug Resistance; Erythropoietin; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Practice Guidelines as Topic; Reference Values; Renal Dialysis; Time Factors; Transferrin

Despite new therapeutic options and treatment strategies, anemia still remains one of the major complications of chronic kidney disease (CKD), especially in patients undergoing chronic hemodialysis for end-stage renal disease. Successful management of anemia is a central part of patient care that may improve clinical outcomes. Although the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) working group reformulated its recommendations by stating that the hemoglobin target in patients receiving erythropoiesis stimulatory agents (ESA) should generally be 11-12 g/dl, this target value can not be achieved in many of them, despite treatment with high doses of ESA. The aim of the present review is to provide an update of the recent literature on causes and possible management of ESA-resistant anemia in CKD patients.

Topics: Anemia; Anemia, Iron-Deficiency; Drug Resistance; Erythropoiesis; Erythropoietin; Hematinics; Humans; Inflammation; Kidney Failure, Chronic; Patient Compliance; Recombinant Proteins; Renal Dialysis

Anaemia is common in congestive heart failure (CHF) and is associated with increased mortality, morbidity and progressive renal failure. The common causes of the anaemia are the associated renal failure and excessive cytokine production, both of which can cause depression of the erythropoietin (EPO) production in the kidney and depression of EPO response in bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. Attempts to control this anaemia will have to consider the use of both erythropoiesis stimulating agents (ESA) as well as oral and, probably more importantly, intravenous (IV) iron. Studies of anaemia in CHF with ESA and oral or IV iron and even with IV iron alone have shown a positive effect on hospitalisation, fatigue and shortness of breath, cardiac and renal function, quality-of-life, exercise capacity and reduced beta natriuretic peptide and have not demonstrated an increase in cardiovascular damage related to therapy. Although some studies and meta-analyses have revealed improvement in these parameters others have not. Adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are needed and are currently being carried out.

Topics: Anemia; Anemia, Iron-Deficiency; Cytokines; Darbepoetin alfa; Electric Countershock; Erythropoietin; Heart Failure; Hematinics; Humans; Iron; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors

Renal dysfunction and neurohormonal and proinflammatory cytokine activation appear to contribute to anemia of chronic disease in most patients, resulting in inappropriate erythropoietin production and defective iron utilization. Under normal conditions, reduced tissue oxygenation caused by chronic anemia results in non-hemodynamic and hemodynamic compensatory responses to enhance oxygen carrying capacity. Erythropoiesis is the predominant non-hemodynamic response to hypoxia, but because erythropoiesis is defective in heart failure, hemodynamic mechanisms may predominate in chronic severe anemia. Hemodynamic responses are complex and involve a vasodilation-mediated high-output state with neurohormonal activation. The high output state initially helps to increase oxygen transport. However, the hemodynamic and neurohormonal alterations could potentially have deleterious long-term consequences and may contribute to anemia's role as an independent risk factor for adverse outcomes.

Topics: Anemia, Iron-Deficiency; Cytokines; Disease Progression; Erythropoietin; Heart Failure; Hemodynamics; Humans; Kidney Failure, Chronic; Prognosis; Renin-Angiotensin System; Risk Factors

Anemia is highly prevalent in patients with chronic heart failure (CHF) and is associated with poor clinical outcome. Increased prevalence of anemia in CHF has been linked to advanced age, female gender, renal function impairment, severity of symptoms, and clinical settings. Overall, the anemia of CHF shares many common features with the anemia of chronic disease. Both impaired iron metabolism and inflammatory stress appear to be the key mediators of the anemia of CHF.

Topics: Age Factors; Anemia, Iron-Deficiency; Disease Progression; Erythropoietin; Female; Heart Failure; Humans; Inflammation; Iron, Dietary; Kidney Failure, Chronic; Male; Prevalence; Prognosis; Renin-Angiotensin System; Risk Factors; Sex Factors; Stress, Physiological; United States

Chronic untreated anemia or iron deficiency (ID) can result in an increased cardiac output, chronic sympathetic activation, left ventricular hypertrophy, and left ventricular dilation, leading to symptomatic chronic heart failure (CHF). Only in the past decade has there been an increase in interest in anemia and ID occurring in the course of CHF. The pharmacologic support in erythropoietin signaling or the correction in iron metabolism may activate molecular pathways that can protect the heart and prevent myocardial remodeling, and hence become a novel therapeutic approach in patients with CHF. Most of the data come from experimental models. Further studies, in particular performed in clinical settings, are warranted.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Heart Failure; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Myocardium; Risk Factors

Anemia resulting from iron and erythropoietin deficiencies is a common complication of advanced chronic kidney disease (CKD). This article covers major advances in our understanding of anemia in patients with CKD, including newly discovered regulatory molecules, such as hepcidin, to innovative intravenous iron therapies. The use of erythropoiesis-stimulating agents (ESA) in the treatment of anemia has undergone seismic shift in the past 3 years as a result of adverse outcomes associated with targeting higher hemoglobin levels with these agents. Potential mechanisms for adverse outcomes, such as higher mortality, are discussed. Despite the disappointing experience with ESAs, there is a tremendous interest in other novel agents to treat anemia in CKD. Lastly, while awaiting updated guidelines, the authors outline their recommendations on how to best manage patients who are anemic and have CKD.

Topics: Anemia, Iron-Deficiency; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cardiovascular Diseases; Erythropoietin; Ferrosoferric Oxide; Heart Failure; Hematinics; Hepcidins; Humans; Indicators and Reagents; Iron, Dietary; Kidney Failure, Chronic

Over the past decade, a growing body of literature has led to a greater understanding of the relationship between anemia and the outcomes in patients with heart failure. This article reviews the current literature on the association between anemia and a broad range of clinical outcomes, including mortality, hospitalization, health status, and cost.

Topics: Anemia, Iron-Deficiency; Disease Progression; Erythropoietin; Health Status; Heart Failure; Hemoglobins; Hospitalization; Humans; Prevalence; Risk Factors; Treatment Outcome; United States

Anemia is a complex issue in patients with heart failure (HF). In past years, clinicians accepted anemia as a given or an "accessory" diagnosis in HF patients. This attitude has changed since understanding of the causes and morbidity of anemia in HF has improved and with the introduction of targeted treatments. Increasing health care costs have stimulated vigorous debate about the cost-effectiveness of such treatments. It behooves clinicians to understand the effectiveness of specific treatments, risks and benefits, and costs. This review addresses the impact of anemia's prevalence, etiology, associated outcomes, and treatments on the economic burden of HF patients.

Topics: Anemia, Iron-Deficiency; Comorbidity; Cost-Benefit Analysis; Erythropoietin; Health Care Costs; Heart Failure; Humans; Prevalence; Quality of Life; Risk Assessment; Treatment Outcome; United States

Anemia in patients with heart failure (HF) may be caused by several factors, including hemodilution, iron or erythropoietin deficiency, and chronic kidney disease. Published pilot studies of erythropoiesis-stimulating agents (ESAs) and intravenous iron therapy in anemic heart failure patients demonstrate improvement in surrogate markers of functional capacity and quality of life, and reasonable safety profile during short-term use. However, the long-term safety of ESA in treatment of anemia in patients with HF remains a concern due to documented harmful side effects of ESA in anemic patients with advanced chronic kidney disease and cancer. Ongoing prospective clinical outcomes studies of ESA and intravenous iron therapies will provide important data that may pave the way for new avenues in the treatment of anemia in the future.

Topics: Anemia, Iron-Deficiency; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Biomarkers; Erythropoietin; Heart Failure; Hematinics; Hemodilution; Hepcidins; Humans; Iron; Quality of Life; Risk Factors; Time Factors; Treatment Outcome

Red blood cells (RBCs) often have a short circulating half-life in hemodialysis patients, which increases the difficulty of achieving a stable hemoglobin level. Fluctuations in erythropoietin (EPO) levels contribute to this increased RBC turnover because a decline in the level of EPO triggers the preferential destruction of newly-formed RBC, a process termed neocytolysis. The RBCs that are released during the treatment of renal anemia are often hypochromic, with a low content of iron; these RBCs are vulnerable to rapid turnover because iron-deficiency affects RBCs in several ways, such as, increased exposure of the phagocytic signaling molecule phosphatidylserine, loss of deformability, and increased oxidative stress. Both EPO fluctuation and the release of iron-deficient RBCs are characteristic events occurring during the management of renal anemia, and the shorter RBC lifetime is a component of the large fluctuations in hemoglobin level seen in patients on hemodialysis.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythrocyte Aging; Erythropoietin; Hemoglobins; Humans; Kidney Diseases; Phagocytosis; Phosphatidylserines; Renal Dialysis

Anemia has been identified as an independent prognostic factor of both morbidity and mortality for patients with congestive heart failure (CHF). The association between anemia and adverse outcomes has raised the hypothesis that anemia correction might lead to an improvement in the prognosis of patients with CHF. Nevertheless, data from large randomized trials about the effect of anemia correction on patient outcome are still lacking. Numerous clinical studies, randomized and nonrandomized, have evaluated the efficacy of erythropoietin or iron supplementation for treating anemia in patients with CHF, and their effect on patient symptoms and functional status. The superiority of any of these approaches has not been established yet. This review will discuss different treatment options for anemic patients with CHF, with emphasis on the correction of iron deficiency.

Topics: Anemia, Iron-Deficiency; Dietary Supplements; Erythropoietin; Heart Diseases; Humans; Iron, Dietary; Randomized Controlled Trials as Topic; Risk Factors

Iron deficiency is prevalent in patients with chronic kidney disease (CKD), and use of oral and intravenous iron in patients with CKD who do not require dialysis might obviate or delay the need for treatment with eythropoiesis-stimulating agents (ESAs). Patients on hemodialysis have lower intestinal iron absorption, greater iron losses, and require greater iron turnover to maintain the ESA-driven red cell mass than do healthy individuals. In these patients, intravenous iron reduces ESA dose requirements and increases the likelihood of maintaining levels of hemoglobin within the desired range. Oral iron is inferior to intravenous iron in patients on hemodialysis, in part because elevated serum levels of hepcidin prevent intestinal absorption of iron. Increased levels of hepcidin also impair the normal recycling of iron through the reticuloendothelial system. Levels of serum ferritin and transferrin saturation below 450 pmol/l and 20%, respectively are indicative of iron deficiency, but values above the normal range lack diagnostic value in patients with CKD on dialysis. The availability of various iron preparations and new developments in delivering iron should enable adequate provision of iron to patients with CKD. This Review examines the efficacy, safety and use of iron supplementation therapy for the treatment of anemia in patients with CKD.

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Erythropoietin; Hematinics; Hepcidins; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

Anaemia is the most frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A disabling complication of IBD, anaemia worsens the patient's general condition and quality of life, and increases hospitalization rates. The main types of anemia in IBD are iron deficiency anemia and anemia of chronic disease. The combination of the serum transferrin receptor with ferritin concentrations and inflammatory markers allows a reliable assessment of the iron status. Iron deficiency is usually treated with oral iron supplements. However, it is less effective in IBD and may lead to an increased inflammatory activity through the generation of reactive oxygen species. A systematic review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on the evidence from recent studies will be the focus of this article.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Ferritins; Humans; Inflammatory Bowel Diseases; Injections, Intravenous; Iron Compounds; Recombinant Proteins; Time Factors; Transferrin

In patients with chronic kidney disease, erythropoietin resistance is common, costly, and has implications beyond the management of anemia because the presence of erythropoietin resistance portends mortal outcomes. Exploring the provenance of erythropoietin resistance may be facilitated by the consideration of the pathogenetic triad of iron-restricted erythropoiesis, inflammation, and bone marrow suppression. Challenging to diagnose because of difficulty in interpreting tests of iron deficiency, iron-restricted erythropoiesis should be considered in patients who require high doses of erythropoietin, have low transferrin saturation (eg, <20%-25%), and do not have very high ferritin (eg, <1,200 ng/mL); a therapeutic trial of intravenous iron may be worthwhile. Aluminum intoxication is a rare cause of iron-restricted erythropoiesis that may manifest as microcytic hypochromic anemia. A decrease in serum albumin concentration may signal the presence of inflammation, which may be manifest (such as because of a recent illness or infection) or occult; the latter include clotted synthetic angioaccess, failed renal allograft, dialysis catheter, periodontal disease, underlying malignancy, or uremia per se. Marrow hyporesponsiveness may be improved by increasing the delivered dialysis dose, using ultrapure dialysate, maintaining adequate vitamin B12 and folate stores, or by treating hyperparathyroidism. In summary, improving the outcomes of erythropoietin-resistant patients will require complete patient assessment that goes beyond considerations of iron and erythropoietin dose alone. Given that erythropoietin dose is associated with mortality, mitigating erythropoietin resistance has the potential to improve patient outcomes.

Topics: Anemia, Iron-Deficiency; Drug Resistance; Erythropoietin; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

The management of anemia in the United States during the past 2 decades and since the introduction of erythropoietin (EPO) has continuously evolved, shaped by the interplay of reimbursement, evidence, clinical performance measurement, and, most recently, risk management. A fee-for-service reimbursement system has driven average EPO doses higher than anywhere else in the world, despite opportunities to decrease such dosing through more effective iron management and subcutaneous administration. Calls by Congress for Medicare to constrain ESA costs and FDA relabeling of erythropoietic-stimulating agents (ESAs), in the wake of The Correction of Hemoglobin and Outcomes in Renal Insufficiency and The Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta trials, have in 2007 led to the first decrease in mean hemoglobin levels in US hemodialysis patients since EPO was introduced in 1989. The implementation of a case-mixed adjusted bundled payment system for ESRD services in 2011 will turn ESAs from a profit center to a cost center for dialysis providers. This is likely to have profound implications regarding anemia management directed at curtailing ESA dosing, including subcutaneous administration, more aggressive iron therapy, and decreased target hemoglobin levels. Medicare has developed a third generation of clinical performance measures (CPMs) for ESRD providers (facilities and physicians) to ensure that quality is maintained in the new fiscal environment. Unlike the previous generations, these new CPMs emphasize an upper limit of hemoglobin as well as a lower one. Payment for performance based on these CPMs will likely be a key driver of future practice patterns for anemia management.

Topics: Anemia, Iron-Deficiency; Drug Costs; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Reimbursement Mechanisms; United States

Treatment for anemia has come a long way in the last 20 years since the first recombinant human erythropoietins were licensed for the management of anemia in chronic kidney disease. The first-generation epoetins were succeeded by the development and production of a longer-acting erythropoietin (EPO) analog, darbepoetin alpha, which allowed less frequent dosing, usually once weekly or once every 2 weeks. More recently, another EPO-related molecule has been manufactured called Continuous Erythropoietin Receptor Activator with an even longer half-life, and although for patent reasons this is not available in the United States, it is licensed and is already being used in Europe. Other molecules are in development or are becoming licensed in Europe, including biosimilar epoetin products/follow-on biologics, and elsewhere in the world there are cheaper-production "copy" epoetins. Indeed, it is estimated that up to 80 such products may be sold in countries with less stringent regulatory control of pharmaceutical products. Two different biosimilar epoetins have already been licensed in Europe, one under 2 different brand names and one under 3 different brand names, and others may follow. Hematide is a synthetic peptide-based EPO receptor agonist that, interestingly, has no structural homology with EPO, and yet is still able to activate the EPO receptor and stimulate erythropoiesis. This agent is currently in phase III clinical trials. Research continues for orally active antianemic therapies, and several strategies are being investigated, although none is imminently available. Two new intravenous iron preparations have recently been developed, one in the United States (Ferumoxytol; AMAG Pharmaceuticals, Inc., Cambridge, MA) and one recently licensed in Europe (ferric carboxymaltose [Ferinject; Vifor Pharma, Zurich, Switzerland]). In conclusion, the development of effective therapies for the treatment of anemia has been a highly active field, both scientifically and economically, over the last two decades.

Topics: Anemia, Iron-Deficiency; Drug Industry; Erythropoietin; Hematinics; Humans; Iron Compounds; Kidney Failure, Chronic; Recombinant Proteins

Anemia has been recognized as a very common and serious comorbidity in heart failure, with a prevalence ranging from 10 to 79%, depending on diagnostic definition, disease severity and patient characteristics. A clear association of anemia with worse prognosis has been confirmed in multiple heart failure trials. This finding has recently triggered intense scrutiny in order to identify the underlying pathophysiology and the best treatment options. Etiology is multifactorial, with iron deficiency and cytokine activation (anemia of chronic disease) playing the most important roles. Treatment is aimed at not only restoring hemoglobin values back to normal, but also at improving the patient's symptoms, functional capacity and hopefully the outcome. Iron supplementation and erythropoietin-stimulating agents have been used for this purpose, either alone or in combination. In this review, the recent advances in elucidating the mechanisms leading to anemia in the setting of heart failure are presented and the evidence supporting the use of different treatment approaches are discussed.

Topics: Anemia; Anemia, Iron-Deficiency; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Cytokines; Erythropoietin; Heart Failure; Hemodilution; Humans; Kidney Diseases; Prevalence; Prognosis

Too often anemia is considered a rare or unimportant manifestation in inflammatory bowel disease (IBD). However, over the last 10 years a number of studies have been conducted and the most relevant conclusions obtained are: (1) anemia is quite common in IBD; (2) although in many cases anemia parallels the clinical activity of the disease, many patients in remission have anemia, and iron, vitamin B12 and/or folic acid deficiency; (3) anemia, and also iron deficiency without anemia, have important consequences in the clinical status and quality of life of the patient; (4) oral iron can lead to gastrointestinal intolerance and failure of treatment; (5) intravenous iron is an effective and safe way to treat iron deficiency; (6) erythropoietin is needed in a significant number of cases to achieve normal hemoglobin levels. Thus, the clinician caring for IBD patients should have a comprehensive knowledge of anemia, and apply recently published guidelines in clinical practice.

Topics: Anemia; Anemia, Iron-Deficiency; Dietary Supplements; Erythropoietin; Humans; Inflammatory Bowel Diseases; Iron; Iron Deficiencies; Prevalence; Quality of Life; Treatment Outcome

Iron and iron plus a recombinant erythropoietin in bloodless medicine often offer a viable and safe alternative to the blood transfusion. But i.v. iron is often underutilised. This particularly applies to pre-operative anaemia which is present in 20% of patients admitted for surgery where iron deficiency is the major contributor. Treatment with i.v. iron, with or without recombinant erythropoietin, reduces the need for peri-operative transfusion.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Injections, Intravenous; Iron; Recombinant Proteins

Anemia is a very common clinical problem in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality in these patients. Erythropoietin is a hormone synthesized that is deficient in the majority of patients with advanced kidney disease, thereby predisposing these patients to anemia. The other cause of anemia is deficiency of iron. Iron deficiency anemia is common in people with CKD and its importance in supporting erythropoiesis is unquestioned, especially in those patients treated with erythropoietin. Intravenous iron is frequently used to treat anemia in CKD patients and is very efficacious in increasing hemoglobin but at the same time there are some safety issues associated with it. The objective of this review is to assess the frequency of adverse drug events associated with four different iron formulations: two iron dextran products known as high and low molecular weight iron dextran, iron sucrose, and sodium ferric gluconate complex. Several electronic databases were searched. In general, with the exception of high molecular weight iron dextran, serious or life-threatening adverse events appeared rare. Iron sucrose has the least reported adverse events and high molecular weight iron dextran has the highest number of reported adverse events. Low molecular weight iron dextran and ferric gluconate fall in between these two for number of adverse drug events.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Databases, Factual; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Iron; Kidney Diseases; Safety

The biology of iron in relation to anemia is best understood by a review of the iron cycle, since the majority of iron for erythropoiesis is provided by iron recovered from senescent erythrocytes. In iron-deficiency anemia, storage iron declines until iron delivery to the bone marrow is insufficient for erythropoiesis. This can be monitored with clinical indicators, beginning with low plasma ferritin, followed by decreased plasma iron and transferrin saturation, and culminating in red blood cells with low-Hb content. When adequate dietary iron is provided, these markers show return to normal, indicating a response to the dietary supplement. Anemia of inflammation (also known as anemia of chronic disease, or ACD) follows a different course, because in this form of anemia storage iron is often abundant but not available for erythropoiesis. The diagnosis of ACD is more difficult than the diagnosis of iron-deficiency anemia, and often the first identified symptom is the failure to show a response to a dietary iron supplement. Confirmation of ACD is best obtained from elevated markers of inflammation. The treatment of ACD, which typically employs erythropoietin (EPO) supplements and intravenous iron (i.v.-iron), is empirical and often falls shorts of therapeutic goals. Dialysis patients show a complex pattern of anemia, which results from inadequate EPO production by the kidney, inflammation, changes in nutrition, and blood losses during treatment. EPO and i.v.-iron are the mainstays of treatment. Patients with heart failure can be anemic, with incidence as high as 50%. The causes are multifactorial; inflammation now appears to be the primary cause of this form of anemia, with contributions from increased plasma volume, effects of drug therapy, and other complications of heart disease. Discerning the mechanisms of anemia for the heart failure patient may aid rational therapy in each case.

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Diseases; Hematinics; Humans; Inflammation; Iron; Kidney Diseases; Male; Recombinant Proteins

The new National Kidney Foundation's Kidney Disease Outcome Quality Initiative clinical practice guidelines for anemia management in chronic kidney disease include several important modifications to the previous recommendations. These changes may have major implications in clinical practice and outcome of the chronic kidney disease patient population. Among the important guideline modifications are the elimination of the upper thresholds for hemoglobin (12 g/dL), transferrin saturation ratio (TSAT, v 50%) and ferritin (800 ng/ml). There are, however, additional recommendations pertaining to anemia management when hemoglobin is above 13 g/dL or serum ferritin above 500 ng/ml. The KDOQI anemia working group explains that the upper ferritin level of 500 ng/ml is not a stopping point for IV iron administration, but adds that decisions regarding IV iron administration should weigh erythropoietin responsiveness, hemoglobin and transferrin saturation level, and the patient's clinical status.The selected upper ferritin level of 500 ng/ml lacks adequate scientific evidence in the CKD population. Approximately half of all maintenance hemodialysis patients in the United States may have a serum ferritin above 500 ng/ml. Serum ferritin in 500-1,200 ng/ml range is not associated with increased death risk in hemodialysis patients if controlled for the confounding effect of malnutrition and inflammation. Given the lack of support from the literature, any attempt to contemplate an upper limit for serum ferritin would be arbitrary, and would not serve to improve the quality of treatment in the CKD population.

Topics: Anemia, Iron-Deficiency; Cause of Death; Drug Monitoring; Erythropoietin; Evidence-Based Medicine; Ferritins; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Patient Selection; Practice Guidelines as Topic; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Risk Factors; Severity of Illness Index; United States

Most patients with chronic kidney disease eventually become anemic. We should view the management of anemia in these patients as part of the overall management of the many clinically relevant manifestations of chronic kidney disease. Erythropoiesis-stimulating agents (ESAs) are safe and should be used, as treating anemia may forestall some of the target-organ damage of chronic kidney disease.

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Kidney Diseases; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis

Iron balance is regulated by the rate of erythropoiesis and the size of the iron stores. Anemia that accompanies infection, inflammation, and cancer (anemia of chronic disease) features normal or increased iron stores, although patients may have functional iron deficiency, namely, an imbalance between iron requirements of the erythroid marrow and the actual supply. The proportion of hypochromic red cells and the hemoglobin content of reticulocytes are direct indicators of functional iron deficiency. Biochemical markers, especially the soluble transferrin receptor/log ferritin ratio (ferritin index), are useful indicators of the iron supply to erythropoiesis. The relationship between functional iron deficiency (reticulocyte hemoglobin content) and iron supply to erythropoiesis (ferritin index) can be described in a diagnostic plot. In normoproliferative and hypoproliferative erythropoiesis, the plot allows the differentiation of classic iron deficiency from anemia of chronic disease and the combined state of functional iron deficiency with anemia of chronic disease. The therapeutic implications of the plot are to differentiate patients into those who should be administered iron supplements, epoetin, or a combination of epoetin and iron. In patients receiving epoetin therapy, the plot is an important tool for monitoring erythropoietic activity, functional iron deficiency, and adequate iron stores for new red cell production. Enhanced erythropoiesis is reflected quantitatively by the ferritin index vector. A transgression of the 1.5 (3.2) cut-off value for the ferritin index indicates that extra doses of iron need to be administered to increase the body's iron stores. A lack of increase or a reticulocyte hemoglobin content below 28 picograms indicates functional iron deficiency. The diagnostic plot is a model for differentiating iron-deficient states and predicting those patients who will respond to epoetin therapy.

Topics: Anemia, Iron-Deficiency; Biomarkers; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron; Iron Deficiencies; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Erythropoiesis; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Treatment Outcome

To review of the prevalence, pathogenesis, diagnosis, and management of iron (Fe)-related anemias in critical illness.. A MEDLINE/PubMed search from 1966 to October 2005 was conducted. References from relevant articles were manually cross-referenced with additional original articles, review articles, correspondence, and chapters from selected textbooks.. Both Fe metabolism and erythropoiesis are affected by the inflammatory response that accompanies critical illness. As a result, many critically ill patients develop the anemia of inflammation, which may be compounded by an underlying Fe deficiency. Most commonly available markers of total body Fe detect Fe deficiency unreliably in the setting of inflammation. Among these tests, the serum transferrin receptor assay is relatively accurate in reflecting total body Fe, regardless of inflammation. Treatment options for Fe-related anemias in critical illness include Fe replacement and recombinant human erythropoietin therapy. The decision to implement these therapies is complex and centers on a critical evaluation of ability to affect anemia, morbidity, and mortality in critical illness and on the potential risks of therapy.. Fe deficiency anemia and the anemia of inflammation may co-exist in critical illness. Diagnosis of and differentiation between these two anemias involves careful interpretation of multiple markers of total body Fe stores. The utility of treatment with both Fe and recombinant human erythropoietin for these disorders during critical illness requires further investigation.

Topics: Anemia, Iron-Deficiency; Critical Illness; Erythropoietin; Humans; Inflammation; Iron; Recombinant Proteins; Transferrin

Despite the proven benefits of intravenous (i.v.) iron therapy in anemia management, it remains underutilized in the hemodialysis population. Although overall i.v. iron usage continues to increase slowly, monthly usage statistics compiled by the US Renal Data System suggest that clinicians are not implementing continued dosing regimens following repletion of iron stores. Continued therapy with i.v. iron represents a key opportunity to improve patient outcomes and increase the efficiency of anemia treatment. Regular administration of low doses of i.v. iron prevents the recurrence of iron deficiency, enhances response to recombinant human erythropoietin therapy, minimizes fluctuation of hemoglobin levels, hematocrit levels, and iron stores, and may reduce overall costs of care. This article reviews the importance of i.v. iron dosing on a regular basis in the hemodialysis patient with iron-deficiency anemia and explores reasons why some clinicians may still be reluctant to employ these protocols in the hemodialysis setting.

Topics: Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Resistance; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Inflammation; Injections, Intravenous; Iron; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Risk Assessment; Treatment Outcome

Intravenous (i.v.) iron and recombinant human erythropoietin (EPO), like all other medications, are associated with the risk of adverse events. Historically, the primary concern with iron therapy has been the possibility of iron overload, which exposes the individual to the effects associated with nontransferrin-bound iron. Experience with EPO use has demonstrated an association with hypertension and with the upregulation of a number of markers of inflammation. The impact of these potential adverse effects merits careful analysis, given that both i.v. iron and EPO are designed for long-term use in a patient population at high risk for infection and cardiovascular disease. However, the incidence of iron overload and the risks associated with nontransferrin-bound iron have dramatically been reduced since the introduction of EPO therapy, and no data exist that demonstrate a definitive association between i.v. iron and an increased risk of morbidity related to infection or cardiovascular disease. On the other hand, EPO use is associated with hypertension, endothelial dysfunction, and prothrombotic and inflammatory states in hemodialysis patients. Risks associated with hypertension can be minimized by using the lowest effective EPO dose, which may be achieved through the regular use of i.v. iron. Judicious use of both i.v. iron and EPO may optimize cardiovascular outcomes.

Topics: Anemia, Iron-Deficiency; Blood Pressure; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Ferritins; Hemoglobins; Hemosiderosis; Humans; Hypertension; Inflammation; Injections, Intravenous; Iron; Patient Care Planning; Recombinant Proteins; Renal Dialysis; Risk Assessment

Anemia in the setting of chronic kidney disease is a well-recognized phenomenon that is associated with decreasing renal function and deficiency of or resistance to erythropoietin. However, anemia in the post-renal transplantation setting has received comparatively less attention in the literature. In this review, we aim critically to appraise the available literature regarding posttransplantation anemia, concentrating in particular on the prevalence of posttransplantation anemia, its etiopathogenesis, potential effects on morbidity and mortality, and the rationale for intervention and treatment. Despite deficiencies in the literature, we conclude that posttransplantation anemia is a common phenomenon that can occur either early or late posttransplantation, and its causation is usually multifactorial and includes contributions notably from poor or decreasing renal function, immunosuppression, and iron deficiency. Conversely, there is a shortage of well-conducted prospective studies looking at the morbidity attributable to posttransplantation anemia and a lack of trial evidence to determine whether intervention improves patient morbidity and outcome.

Topics: Anemia, Iron-Deficiency; Cardiovascular Diseases; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Prevalence; Recombinant Proteins; Risk Factors

Uraemic patients are exposed either to iron deficiency due to impaired digestive n associated with various blood losses (particularly in dialysis patients) or iron verload related to blood transfusions in the pre-erythropoetin era or excessive intravenous iron supplementation. The central role of hepcidin in the regulation of oral iron absorption d its effects in uraemia have been recently evidenced. The increased haemoglobin synthesis induced by erythropoiesis stimulating agents (ESA) enhances iron requirements. In case of exhaustion of tissue reserves and/or insufficient exogenous supply, iron deficiency develops which is the major limiting factor for ESA efficacy. Careful biological follow-up is mandatory to detect early iron deficiency or overload, the latter being considered as possibly increasing the uraemic patients' susceptibility to bacterial or viral infections. Intravenous administration of Vitamin C, by enhancing the release of iron from the reticuloendothelial system towards transferrin increases the circulating iron available for erythropoiesis and contributes to the optimisation of ESA efficacy.

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Ascorbic Acid; Erythropoietin; Hepcidins; Humans; Intestinal Absorption; Iron; Iron Deficiencies; Uremia

This paper reviews literature data on iron replacement (loading) for peritoneal dialysis patients. The 3 main sources of clinical guidelines (American NKF-K/DOQI, European EBPG and French AFSSAPS) agree about the definition of iron deficience, but are not similar about the haemoglobin/hematocrit targets for EPO treatment, and for the route of iron administration (oral versus intravenous). Iron requirements are less in PD HD patients. That could be explained by several factors: less blood losses, preservation of a residual renal function, better digestive iron absorption due to a greater hepcidin excretion. Intravenous route for iron sucrose is more efficient than oral route. Taking into account the iron requirements for PD patients, monthly 200 mg iron sucrose infusions over 5 mn seem to be safe and sufficient for most patients.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Europe; France; Humans; Iron; Kidney Failure, Chronic; Kidney Function Tests; Peritoneal Dialysis; Renal Dialysis; United States

Topics: Anemia; Anemia, Iron-Deficiency; Creatinine; Darbepoetin alfa; Disease Progression; Erythropoietin; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis

When erythropoietin (epoetins or darbepoetin) is used to treat the anemias of chronic renal failure, cancer chemotherapy, inflammatory bowel diseases, HIV infection and rheumatoid arthritis, functional iron deficiency rapidly ensues unless individuals are iron-overloaded from prior transfusions. Therefore, iron therapy is essential when using erythropoietin to maximize erythropoiesis by avoiding absolute and functional iron deficiency. Body iron stores (800-1200 mg) are best maintained by providing this much iron intravenously in a year, or more if blood loss is significant (in hemodialysis patients this can be 1-3 g). There is no ideal method for monitoring iron therapy, but serum ferritin and transferrin iron saturation are the most common tests. Iron deficiency is also detected by measuring the percentage of hypochromic red blood cells, content of hemoglobin in reticulocytes, soluble transferrin receptor levels, and free erythrocyte protoporphyrin values, but iron overload is not monitored by these tests. Iron gluconate and iron sucrose are the safest intravenous medications.

Topics: Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Ferritins; Humans; Iron; Monitoring, Physiologic; Transferrin

Colorectal cancers are classically revealed by a low digestive bleeding, which can be occult or exteriorized. They commonly present anemia at the diagnosis leading to particular outcomes. Perioperative blood transfusions are frequently indicated for the treatment of localized tumors and for hepatic resection of metastatic lesions but transfusions seem to have a negative impact on prognosis by increasing infections and potentially recurrence. In this context, various strategies aim at limiting the transfusional risk (autologous transfusion, preoperative use of erythropoietin...). Anemia associated with advanced colorectal cancers provides the same interest as for any metastatic tumor, as quality of life of patients is correlated to the hemoglobin's level.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Colorectal Neoplasms; Erythropoietin; Gastrointestinal Hemorrhage; Humans; Recombinant Proteins; Rectum; Transfusion Reaction

Anemia is a common complication of chronic kidney disease, particularly in patients who are on dialysis. The use of recombinant human erythropoietin has led to the eradication of severe anemia in the dialysis population. Correction of anemia in these patients has been associated with better quality of life and clinical outcomes. Some hemodialysis patients have anemia that either is relatively refractory to epoetin therapy or requires very high doses of epoetin (i.e., hyporesponsiveness), despite having adequate iron stores, and are thus unable to achieve or maintain target hemoglobin levels. Several pharmacologic agents have been studied for effects on improving response to epoetin, either to counter hyporesponsiveness or simply to reduce epoetin use for purely economic reasons. This review examines the available literature regarding the efficacy of these potential pharmacologic adjuvants to epoetin in the treatment of anemia in patients on maintenance hemodialysis, with special emphasis on androgens, vitamin C (ascorbic acid), and L-carnitine. A review of published guidelines and recommendations for use of these agents in hemodialysis patients is provided.

Topics: Adjuvants, Pharmaceutic; Androgens; Anemia, Iron-Deficiency; Antioxidants; Ascorbic Acid; Carnitine; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male; Practice Guidelines as Topic; Renal Dialysis; Treatment Outcome

Anaemia has a detrimental impact on quality of life and it is important that this condition is recognised and treated in patients with cancer. Epoetin beta is an effective and well-tolerated treatment of anaemia in patients with a wide range of solid and haematological malignancies. A study in patients with lymphoid malignancies confirms that epoetin beta is equally effective at the same overall weekly dose (30,000 IU weekly) when given once-weekly or three-times weekly. This once-weekly regimen has also proved effective in patients with solid tumours. Once-weekly treatment is more convenient for the patient, potentially improving compliance and is associated with reduced hospital administration costs. The majority of patients with cancer will respond to epoetin therapy with an increase in haemoglobin levels. However, it is of value to identify those patients who are likely to respond, so that cost-effectiveness can be improved. Despite much research into potential predictive factors, follow-up studies are required and clinical judgement remains key to managing the anaemia of cancer. In addition, studies suggest that intravenous iron supplementation can improve response to epoetin therapy in patients with functional iron deficiency. Epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer. Ongoing studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Erythropoietin; Hematologic Neoplasms; Humans; Iron Compounds; Multivariate Analysis; Neoplasms; Predictive Value of Tests; Quality of Life; Recombinant Proteins; Treatment Outcome

The incidence of both congestive heart failure (CHF) and end-stage renal disease both are increasing. Anemia is common in both conditions and is associated with a marked increase in mortality and morbidity in both CHF and chronic kidney insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2. In other words, a vicious circle frequently is present in which CHF can cause or worsen both anemia and CKI, in which CKI can cause or worsen both anemia and CHF, and in which anemia can cause or worsen both CHF and CKI. We have called this vicious circle the cardio renal anemia syndrome. Optimal treatment of CHF with all the recommended CHF medications at their recommended doses will, in our experience, frequently fail to improve the CHF and CKI if anemia is present and is not corrected. On the other hand, correction of the anemia with subcutaneous erythropoietin and intravenous iron has caused a great improvement in the CHF including a marked improvement in patient and cardiac function and a marked reduction in the need for hospitalization and for high-dose diuretics. It also frequently has caused renal function to improve or at least stabilize. In addition, patients' quality of life and exercise capacity also have improved with the correction of the anemia. In CKI patients, anemia also may play an important role in increasing the risk for death, coronary heart disease, stroke, and progression to end-stage renal disease. Erythropoietin may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell apoptosis and by increasing neovascularization, both of which could prevent tissue damage. This could have profound therapeutic implications not only in CHF but in the future treatment of myocardial infarction, coronary heart disease, strokes, and renal failure.

Topics: Age Factors; Aged; Anemia, Iron-Deficiency; Animals; Cohort Studies; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Follow-Up Studies; Heart Failure; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome

The correction of anemia in dialysis patients with erythropoietin (EPO) can be frustrated by insufficient iron. To address this effect, we preloaded candidate EPO patients with intravenous iron in the early 1990s. Preloading with 900-1,525 mg of iron yielded the following results: 70% of patients had increasing hematocrits (HCTs) without EPO, and 40% of patients had HCTs greater than 30%. Apparent lack of iron led to blood loss studies. Routes evaluated were blood sampling, dialyzer clotting, blood in the dialyzer circuit and postdialysis bleeding. Projected annual losses were between 2,516 and 5,126 ml, depending on circuit and posttreatment losses. In terms of red cell loss, the results are comparable to those in the early days of dialysis before the introduction of current technology. Extension of these studies to daily dialysis predicts possible losses with this 6 times a week therapy of between 4,663 and 9,884 ml per year.

Topics: Anemia, Iron-Deficiency; Blood Coagulation; Catheters, Indwelling; Erythropoiesis; Erythropoietin; Hemorrhage; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Models, Biological; Premedication; Recombinant Proteins; Renal Dialysis

The formation of red blood cells (RBCs) in the bone marrow is regulated by erythropoietin in response to a cascade of events. Anemia in the intensive care unit can be caused by a host of factors. Patients in the intensive care unit may have decreased RBC production and a blunted response to erythropoietin. Administration of recombinant human erythropoietin may stimulate erythropoiesis, increase hematocrit levels and hemoglobin concentration, and reduce the need for RBC transfusions.

Topics: Anemia; Anemia, Iron-Deficiency; Blood Specimen Collection; Bone Marrow Cells; Comorbidity; Erythrocytes; Erythroid Precursor Cells; Erythropoietin; Hemorrhage; Humans; Incidence; Intensive Care Units; Vitamin B 12 Deficiency

Iron deficiency anaemia is one of the most common disorders in the world. Also, one third of inflammatory bowel disease (IBD) patients suffer from recurrent anaemia. Anaemia has significant impact on the quality of life of affected patients. Chronic fatigue, a frequent IBD symptom itself, is commonly caused by anaemia and may debilitate patients as much as abdominal pain or diarrhoea. Common therapeutic targets are the mechanisms behind anaemia of chronic disease and iron deficiency. It is our experience that virtually all patients with IBD associated anaemia can be successfully treated with a combination of iron sucrose and erythropoietin, which then may positively affect the misled immune response in IBD.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Fatigue; Folic Acid; Humans; Inflammatory Bowel Diseases; Iron; Quality of Life; Recombinant Proteins; Vitamin B 12 Deficiency

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Biomarkers; Drug Resistance; Erythropoietin; Ferritins; Humans; Iron; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; Renal Dialysis; Transferrin

Postpartum anaemia is associated with breathlessness, tiredness, palpitations and maternal infections. Blood transfusions or iron supplementation have been used in the treatment of iron deficiency anaemia. Recently other anaemia treatments, in particular erythropoietin therapy, have also been used.. To assess the clinical effects of treatments for postpartum anaemia, including oral, intravenous or subcutaneous iron/folate supplementation and erythropoietin administration, and blood transfusion.. We searched the Cochrane Pregnancy and Childbirth Group trials register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), Current Contents and ACP Journal Club (from inception to March 2003).. Randomised controlled trials (RCTs) comparing therapy for postpartum iron deficiency anaemia (oral, intravenous or subcutaneous administration of iron, folate, erythropoietin or blood transfusion) with placebo, another treatment or no treatment.. Two reviewers independently assessed trial quality and extracted data.. Six included RCTs involving 411 women described treatment with erythropoietin or iron as their primary interventions. No RCTs were identified that assessed treatment with blood transfusion. Few outcomes relating to clinical maternal and neonatal factors were reported: studies focused largely on surrogate outcomes such as haematological indices. Overall, the methodological quality of the included RCTs was reasonable; however, their usefulness in this review is restricted by the interventions and outcomes reported. When compared with iron therapy only, erythropoietin increased the likelihood of lactation at discharge from hospital (1 RCT, n = 40; relative risk (RR) 1.90, 95% confidence interval (CI) 1.21 to 2.98). No apparent effect on need for blood transfusions was found, when erythropoietin plus iron was compared to treatment with iron only (2 RCTs, n = 100; RR 0.20, 95% CI 0.01 to 3.92), although the RCTs may have been of insufficient size to rule out important clinical differences. Haematological indices (haemoglobin and haemocrit) showed some increases when erythropoietin was compared to iron only, iron and folate, but not when compared with placebo.. There is some limited evidence of favourable outcomes for treatment of postpartum anaemia with erythropoietin. However, most of the available literature focuses on laboratory haematological indices, rather than clinical outcomes. Further high-quality trials assessing the treatment of postpartum anaemia with iron supplementation and blood transfusions are required. Future trials may also examine the significance of the severity of anaemia in relation to treatment, and an iron-rich diet as an intervention.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Iron; Puerperal Disorders; Randomized Controlled Trials as Topic

Anemia complicates the course of disease in about 50% of patients with cancer, and negatively affects their quality of life. A correct approach to therapy should consider all the possible causes and patients need to be treated accordingly. The observation that erythropoietin production is often blunted offers new treatment possibilities. Fifty to 70% of anemic patients respond to rHuEpo, given in a three times or once-a-week schedule. The novel hyperglycosylated protein darbepoetin permits longer intervals between administrations, thanks to its longer half-life, and a once per cycle or once-a-month schedule is a reasonable target. Correction of anemia improves the quality of life, and it has been hypothesized that improvement of cognitive function may derive from a direct effect of Epo on CNS cells. Although anemia is an adverse prognostic factor in cancer, results of recent clinical trials have raised the question whether rHuEpo may favor neoplastic cell proliferation. Results are conflicting at the moment, and further studies are required before arriving at a conclusion. Data available so far do not indicate any negative effect of darbepoetin on the outcome of cancer disease, nor has the production of anti-darbepoetin antibodies or PRCA been reported, a complication observed in less than 200 patients with anemia due to renal insufficiency and treated with rHuEpo alpha.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Over the past few years, anemia has emerged as a powerful independent predictor of adverse outcomes in chronic heart failure (CHF). It affects up to 50% of patients with CHF, depending on the definition of anemia used and on the population studied. Even small reductions in hemoglobin are associated with worse outcome. However, the causes of anemia in CHF remain unclear, although impairment of renal function and inflammatory cytokines are proposed mechanisms. Both may act through impairment of the synthesis or action of erythropoietin. Preliminary studies have demonstrated improvement in symptoms, exercise tolerance, quality of life, and reductions in hospitalizations when patients with severe CHF were treated with erythropoietin. The benefits and the potential risks of such therapies will be further addressed in upcoming larger randomized trials. The recent interest in anemia reflects a new perspective in heart failure therapy, focusing on non-cardiovascular comorbidities.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cytokines; Erythropoietin; Female; Heart Failure; Hemodilution; Humans; Kidney Failure, Chronic; Male; Prevalence; Prognosis; Risk Factors

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.

Topics: Anemia; Anemia, Iron-Deficiency; Azathioprine; Bone Marrow; Child; Erythropoiesis; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus

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.

Topics: Anemia, Iron-Deficiency; Animals; Biomarkers; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Humans; Iron; Iron Deficiencies; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis

Recent epidemiologic studies show that iron deficiency occurs in the vast majority of patients with chronic kidney disease (CKD). In patients with CKD, increased iron losses and, to a lesser extent, poor oral absorption, can lead to iron-deficiency anemia. Correction of iron-deficiency anemia is preferable by the oral route, however, data on oral iron use are limited in this population. In CKD patients, parenteral iron administered with recombinant human erythropoietin (rHuEpo), is the best potential option for the correction of anemia. Nondextran iron preparations are preferable because of a reduced incidence of serious adverse events. Parenteral iron in CKD patients may not be entirely innocuous and, although commonly used, have not received Food and Drug Administration approval for use in this patient population. Exposure to intravenous (IV) iron may lead to oxidative stress, renal injury, infection, cardiovascular disease, and osteomalacia. Studies are needed to confirm the existence and magnitude of these complications. The current data suggest that the overall risk-benefit ratio favors use of IV iron when compared with untreated or partially treated iron-deficiency anemia.

Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Erythropoietin; Humans; Infections; Iron; Kidney Failure, Chronic; Oxidative Stress; Recombinant Proteins

About half of all the patients with CHF are anemic (they have a hemoglobin of < 12 g%). The prevalence and severity of this anemia increase with increasing severity of the CHF. The anemia is caused by a combination of poor nutrition, associated renal insufficiency causing inappropriately low Erythropoietin (EPO) levels, bone marrow depression and EPO resistance caused by excessive TNF alpha and other factors, gastrointestinal blood loss caused by aspirin, ACE inhibitors, EPO loss in the urine with proteinuria, and hemodilution caused by the excessive plasma volume. Studies have shown that the anemia is an independent risk factor for death in CHF, almost doubling the mortality rate. Correction of the anemia with subcutaneous EPO and IV iron improves cardiac function and functional capacity, helps prevent the progression of renal failure, markedly reduces hospitalization and diuretic doses, and improves self assessed quality of life. This so-called Cardio Renal Anemia Syndrome is very common in CHF. Its successful treatment demands close cooperation between cardiologists and nephrologists.

Topics: Anemia, Iron-Deficiency; Comorbidity; Erythropoietin; Female; Heart Failure; Humans; Incidence; Iron Compounds; Male; Prognosis; Recombinant Proteins; Risk Factors; Severity of Illness Index; Survival Rate; Treatment Outcome

Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non-heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron-deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron-binding proteins and immature antioxidant systems.. The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.

Topics: Anemia, Iron-Deficiency; Combined Modality Therapy; Erythrocyte Transfusion; Erythropoietin; Female; Fetal Growth Retardation; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Iron Compounds; Iron Metabolism Disorders; Iron Overload; Maternal-Fetal Exchange; Perinatology; Pregnancy; Recombinant Proteins; Risk Assessment; Risk Factors; Severity of Illness Index

The effectiveness of anemia management in patients with end stage renal disease (ESRD) has increased over the past 4 years. However, approximately 26% of treated patients still do not meet the minimum hemoglobin (Hgb) value of 11 g/dl that is recommended by the K/DOQI Clinical Practice Guidelines (National Kidney Foundation [NKF], 2001). One of the main obstacles to good patient outcome may be iron deficiency, which is common in both the predialysis and dialysis period. Since iron is needed for Hgb synthesis, iron depletion exacerbated anemia and reduces the response to recombinant erythropoietin (rEPO) therapy. Health care providers can significantly improve patient outcome by addressing iron deficiency more rigorously. A good starting point is the establishment of an iron deficiency management protocol that includes early evaluation of iron status and aggressive iron therapy. Iron therapy, in turn, can be optimized by administering safe and effective iron supplements and by implementing maintenance iron regimens to prevent the recurrence of iron deficiency. By making these simple improvements to their treatment approach, clinicians can enhance the effectiveness of anemia management in patients with ESRD.

Topics: Algorithms; Anemia, Iron-Deficiency; Decision Trees; Drug Monitoring; Erythropoietin; Ferritins; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Patient Care Planning; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Female; Humans; Inflammatory Bowel Diseases; Iron; Male; Recombinant Proteins

The development of a stepwise therapy, as detailed below, can be administered to the mostly young patients with Crohn's disease and ulcerative colitis on an out-patient basis and appropriate to their needs. This is true not only for the activity of the disease, but also for extraintestinal manifestations. The numerous variations in the stepwise anti-inflammatory therapy of chronic inflammatory bowel disease, but also in the substitution therapy of deficiency states and the therapy of accompanying extraintestinal diseases provide the gastroenterologist with the possibility of a long-term treatment tailored to the needs of the individual patient.

Topics: Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Ferric Compounds; Ferrous Compounds; Humans; Recombinant Proteins

More than a decade has passed since the first patient with end-stage renal failure was treated with erythropoietin (EPO) and more than 85% of patients now receive this therapy. In the year 2002 more than 60% of dialysis patients will be elderly, and the treatment of anemia will be more complex due to the aditional causes: folate, iron and vitamin deficiency in this population. Correction of anemia with EPO brings about partial regression of left ventricular hypertrophy and some data suggest that such treatment reduces cardiovascular mortality in patients without advance cardiac disease. Normalization of hematocrit with EPO increases oxygen supply to the brain tissue with improvement in brain function. The improvement in the ability to recognize, discriminate and hold stimuli in memory for difficult tasks is particularly important for elderly people. No differences have been noted in the incidence of clotting of vascular access in patients treated with EPO compared with hemodialysis patients not so treated. Also no one has demostrated that treatment with EPO accelerates renal decline in patients with progressive renal insufficiency. In elderly people with anemia secondary to advanced renal failure, EPO therapy improves physical, cognitive and sexual function, and health related quality of life.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Prognosis; Quality of Life; Renal Dialysis; Risk Assessment; Treatment Outcome

Anaemia is common in patients with haematological malignancy, occurring in the majority of patients with malignant disease who are treated with chemotherapy. Most patients will have their anaemia attributed to the cytokine-mediated anaemia of chronic disease. Many of these patients with anaemia will be symptomatic with fatigue, which is the single most important symptom reported. Data from many studies indicate that treatment of patients with anaemia with recombinant human erythropoietin (rHuEpo) will increase their haemoglobin level, decrease transfusion need and also improve their quality of life. Recent clinical and experimental work suggest that improving the haemoglobin level may improve the patients' prognosis but this finding needs to be confirmed. Treatment of anaemia with rHuEpo in patients with cancer may produce many benefits. Unfortunately, rHuEpo is effective in only around 60% of patients, is slow acting and is expensive. These drawbacks have restricted its use in many healthcare systems. However, a failure to treat anaemia may have important adverse effects for the patient both in terms of their quality of life and, just possibly, in terms of their life expectancy.

Topics: Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis

Anemia associated with end stage renal disease can diminish quality of life substantially. Maintaining a stable hematocrit and stable hemoglobin levels affords many advantages. Improvement of anemia management is possible with the implementation of continuous quality improvement (CQI). Our review of the literature motivated us to switch from iron dextran injection, which can induce anaphylactic reactions and has other associated problems, to sodium ferric gluconate complex injection. This enables us to safely provide iron supplementation without the precautions that were in place for iron dextran. Our methods for creating and implementing CQI in the dialysis program at our university hospital are described.

Topics: Algorithms; Anaphylaxis; Anemia, Iron-Deficiency; Decision Trees; Erythropoietin; Ferric Compounds; Ferritins; Hemoglobins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Renal Dialysis; Total Quality Management; Transferrin

Anemia is a frequent problem in patients with chronic kidney disease (CKD) who are not yet receiving dialysis and can lead to major health complications is left untreated. The successful management of these patients entails repletion of iron stores, often through use of intravenous iron, particularly in patients receiving erythropoietin therapy. To encourage patient compliance with anemia management protocols, the nephrology nurse can play a key role in patient education in reducing barriers to proper management and in raising the awareness of the benefits of treating this condition.

Topics: Algorithms; Anemia, Iron-Deficiency; Creatinine; Decision Trees; Drug Monitoring; Erythropoietin; Ferrous Compounds; Hematocrit; Humans; Kidney Failure, Chronic; Nurse's Role; Patient Education as Topic; Renal Dialysis; Risk Factors

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative and other groups support maintaining transferrin saturation (TSAT) levels above 20% and serum ferritin levels above 100 ng/ml to ensure adequate erythropoiesis in hemodialysis patients receiving erythropoietin. However, researchers have found that even patients with TSATs above 20% may still have functional iron deficiency. This article presents information that supports the fact that maintenance of TSATs between 30% and 50%, through the use of continuous intravenous iron therapy, results in improvement of anemia, reduction in erythropoietin dose requirements, and an increase in the reticulocyte hemoglobin content. The implications of these findings for clinical practice are also discussed.

Topics: Algorithms; Anemia, Iron-Deficiency; Clinical Protocols; Decision Trees; Drug Monitoring; Erythropoietin; Evidence-Based Medicine; Ferritins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Renal Dialysis; Total Quality Management; Transferrin; Treatment Outcome

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative recommends a target hemoglobin (Hb) level of 11 to 12 g/dL (hematocrit [Hct] of 33% to 36%) for both peritoneal dialysis and hemodialysis patients. However, national tracking data indicate that peritoneal dialysis patients have consistently lower Hb/Hct levels. This article focuses on anemia management challenges that are unique to the peritoneal dialysis population. Nursing knowledge and management of Epoetin alfa dosing and administration techniques, peritonitis and other infections, and iron supplementation may help improve anemia-related outcomes in peritoneal dialysis patients.

Topics: Adult; Anemia, Iron-Deficiency; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Peritoneal Dialysis; Recombinant Proteins; Total Quality Management

Both anaemia of iron deficiency and anaemia of chronic disease are frequently encountered in inflammatory bowel disease. Anaemia of iron deficiency is mostly due to inadequate intake or loss of iron. Anaemia of chronic disease probably results from decreased erythropoiesis, secondary to increased levels of proinflammatory cytokines, reactive oxygen metabolites and nitric oxide. Assessment of the iron status in a condition associated with inflammation, such as inflammatory bowel disease, is difficult. The combination of serum transferrin receptor with ferritin concentrations, however, allows a reliable assessment of the iron deficit. The best treatment for anaemia of chronic disease is the cure of the underlying disease. Erythropoietin reportedly may increase haemoglobin levels in some of these patients. The anaemia of iron deficiency is usually treated with oral iron supplements. Iron supplementation may lead to an increased inflammatory activity through the generation of reactive oxygen species. To date, data from studies in animal models of inflammatory bowel disease support the theoretical disadvantage of iron supplementation in this respect. The results, however, cannot easily be extrapolated to the human situation, because the amount of supplemented iron in these experiments was much higher than the dose used in patients with iron deficiency.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Dietary Supplements; Erythropoietin; Ferritins; Humans; Inflammatory Bowel Diseases; Iron; Receptors, Transferrin

Intravenous iron has been found to be an important adjunctive therapy in the treatment of anemia for patients on dialysis. In the United States, iron dextran had been the only form available for parenteral use until 1999. This agent has been associated with a concerning number of severe adverse reactions, in some cases resulting in patients' deaths. Recently, a form of iron used for many years in Europe, sodium ferric gluconate complex in sucrose, was approved for intravenous use in the United STATES: Because this agent does not contain the immunogenic dextran component of iron dextran, it is expected that the safety profile of this drug should be superior to that of iron dextran. The purpose of this review is to critically appraise the relevant literature and to synthesize the information into a strategy for clinical use of this drug.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Humans; Infusions, Intravenous; Injections, Intravenous; Iron; Iron-Dextran Complex; Recombinant Proteins; Renal Dialysis; Transferrin

Anaemia is one of the most common risk factors in the area of obstetrics and perinatal medicine. During pregnancy and in the puerperium it is associated with an increased incidence of both maternal and fetal morbidity and mortality, the extent of which is dependent upon the severity of anaemia and the resulting complications. In order to correctly diagnose the type and degree of anaemia, a prerequisite for selection of the proper therapy, one must first of all correctly differentiate between the relative, i.e., the physiological anaemia of pregnancy due to the normal plasma volume increase during pregnancy, and "real anaemias" with various different pathophysiological causes. When defining the Hb cutoff value for anaemia in pregnancy, the extent of the plasma volume changes with respect to the gestational age must be taken into consideration. It has been found that haemoglobin values < 11.0 g/dl in the first and third trimesters, and < 10.5 g/dl in the second trimester may point to an anaemic situation which should be further clarified. The first important steps for diagnosing anaemia in a pregnant patient include a thorough check of her medical history and a medical examination. This procedure often lays the basis for a correct diagnosis. The current gold standard to detect iron deficiency remains the serum ferritin value. To be reliable, this requires the ruling out of an infection (chronic or acute) as a cause of the anaemia. We recommend a complete laboratory test for the exact haematological status as well as the assessment of specific chemical laboratory parameters. These should include a palette of additional, promising new parameters such as hypochromic red cells and transferrin receptors which allow more accurate detection of iron deficiency and differential diagnosis of iron deficiency anaemia. After correct diagnosis, major emphasis should be put on safe and effective treatment of anaemia which again depends on severity of anaemia, time for restoration and patients characteristics. Today effective alternatives to oral iron only or blood transfusion such as parenteral iron sucrose complex and in selected cases also recombinant erythropoietin have been investigated and show promising results concerning effective treatment of anaemia during pregnancy and postpartum.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Diagnosis, Differential; Erythropoietin; Female; Hemoglobinometry; Humans; Infant, Newborn; Iron; Plasma Volume; Pregnancy; Pregnancy Complications, Hematologic; Recombinant Proteins; Reference Values

Stimulation of red blood cell precursors by Epoetin alfa results in a predictable, dose-dependent increase in red blood cell mass. Iron is an important substrate that supports red blood cell and hemoglobin development. Patients who receive Epoetin alfa therapy typically require intravenous iron supplementation to ensure proper red cell formation. Target and ceiling iron levels should be determined on the basis of safety considerations, the predicted clinical response, and individual patient replacement needs. Nurses can use clinical parameters such as body weight, baseline and target hemoglobin values, and iron losses from blood and other sources to estimate iron replacement doses, thereby providing a guide for appropriate iron replacement.

Topics: Anemia, Iron-Deficiency; Body Weight; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Hematinics; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Iron Compounds; Iron Overload; Kidney Failure, Chronic; Nurse's Role; Nursing Assessment; Recombinant Proteins; Renal Dialysis; Safety Management; Transferrin

Since many end stage renal disease (ESRD) patients experi inflammation, malnutrition, and anemia, the interplay of these processes should be considered in the approach to patients treated with erythropoietin (EPO). This article reviews the interrelationship between these factors. The systemic inflammatory response caused by exposure to inflammatory stimuli results in anorexia and metabolic disturbances leading to protein calorie malnut tion as well as sequestration of iron and hyporesponsiveness to EPO. The implications of these effects and possible strategies to optimize anemia management in the presence of these conditions are discussed.

Topics: Anemia, Iron-Deficiency; Clinical Protocols; Drug Monitoring; Erythropoietin; Ferritins; Hematinics; Humans; Iron; Iron-Binding Proteins; Iron-Dextran Complex; Kidney Failure, Chronic; Nutritional Status; Nutritional Support; Protein-Energy Malnutrition; Risk Factors; Systemic Inflammatory Response Syndrome; Treatment Outcome

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

Better anemia management has dramatically improved the lives of many patients with end stage renal disease (ESRD). Nephrology professionals frequently use two tools--erythropoietin and supplemental iron--to manage anemia. The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) suggests that most ESRD patients will need intravenous (i.v.) iron to optimize their response to erythropoietin. In this report, the author reviews published studies showing that i.v. iron reduces erythropoietin dose requirements, resulting in cost savings. She presents data from her center illustrating that i.v. administration of the newly approved Ferrlecit (sodium ferric gluconate) also improves anemia management and reduces erythropoietin dose requirements. The author reviews studies showing the efficacy of i.v. iron as monotherapy for anemia in ESRD patients. These data support the importance of i.v. iron as an agent to be used alone or in conjunction with erythropoietin in the management of anemia in patients with ESRD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost Savings; Drug Administration Schedule; Drug Costs; Drug Monitoring; Erythropoietin; Female; Ferric Compounds; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis; Time Factors

Since the introduction of recombinant human erythropoietin (rHuEPO) into clinical nephrology practice 10 years ago, there has been a slow increase in hemoglobin (Hgb) levels, but most patients with the anemia of chronic renal failure are still moderately anemic and have not achieved the target Hgb (11 to 12 g/dL) recommended by the NKF-DOQI anemia guidelines. Functional iron deficiency, insufficient rHuEPO doses and comorbid factors such as inflammation/infection have been the major reasons for not achieving this target. By optimizing iron stores with regular infusions of intravenous iron in the hemodialysis patient (who has significant blood [iron] losses related to the hemodialysis procedure), and giving adequate amounts of rHuEPO, preferably subcutaneously instead of intravenously, the NKF-DOQI recommended target Hb can be achieved in the majority of patients so treated.

Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Erythropoietin; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Practice Guidelines as Topic; Prognosis; Recombinant Proteins; Renal Dialysis; Treatment Outcome; United States

Topics: Administration, Oral; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Outcome Assessment, Health Care; Prognosis; Recombinant Proteins; Renal Dialysis; Treatment Outcome

It has been 10 years since epoetin-alpha was approved by the federal Food and Drug Administration for use in end-stage renal disease patients. Over this period of time, clinical studies have shown a relationship between the correction of anemia and improved cardiac function, cognitive ability, sexual function, and exercise capacity. Recent large epidemiological studies have shown that mortality and morbidity are reduced when the hematocrit (Hct) level is in the range 33% to 36%, and the National Kidney Foundation's Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines recommend a target Hct of 33% to 36% to enhance patient outcomes. The most recent mortality studies show that Hcts less than 30% (or hemoglobins less than 110 gm/L) are associated with an 18% to 40% increased associated risk of death and hospitalizations. Higher Hcts in the 33% to 36% range appear to be associated with a 7% reduced risk of death and hospitalizations compared with patients with Hcts of 30% to less than 33%. Patients with sustained Hcts of 33% to 36% over 1 year appear to have the best outcome compared with patients with Hcts that fall. These studies suggest that the factors that may influence patients' ability to move into higher Hct ranges need to be determined to enhance patient outcomes. Dramatic improvement in hemodialysis patient Hct levels has occurred since 1989. Mortality and hospitalization studies support the NKF-DOQI target Hct range of 33% to 36% as providing the best associated outcomes.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Morbidity; Prognosis; Recombinant Proteins; Risk Assessment; Survival Analysis

Cardiovascular disease is a major cause of mortality and morbidity in patients with end-stage renal disease. Anemia, a result of erythropoietin deficiency, is associated with increased all-cause and cardiovascular mortality in this population, and predisposes patients to the development of symptomatic heart disease. Anemia is also associated with the development and progression of left ventricular echocardiographic disorders, which strongly predict cardiac failure and death. Left ventricular dilatation with compensatory hypertrophy, the major pattern of echocardiographic disease progression in hemodialysis patients, is a particularly strong predictor of late mortality. Partial correction of anemia with recombinant human erythropoietin likely reduces left ventricular mass and volume. Complete correction of anemia may prevent progressive left ventricular dilatation in patients with normal left ventricular volumes. A recent trial, however, reports excess mortality and vascular access loss in patients with preexisting symptomatic heart disease when anemia was completely corrected. Consequently, hematocrit target ranges above 32% to 36% cannot be recommended in this population. In patients without symptomatic heart disease, it is not possible to conclude that potential benefits derived from a normalized hematocrit will outweigh potential risks.

Topics: Anemia, Iron-Deficiency; Cardiovascular Diseases; Comorbidity; Echocardiography; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Prognosis; Recombinant Proteins; Renal Dialysis; Risk Factors; Survival Analysis

Since its introduction for clinical use a decade ago, recombinant human erythropoietin (rHuEPO) has revolutionized the management of the anemia of end-stage renal disease. Soon after its release, it became evident that the biological targets of rHuEPO were not limited to the erythroid progenitor cells. Instead, numerous clinical and laboratory studies have shown the modulatory action of rHuEPO on a wide array of cell types and organ systems. The present article is intended to provide an overview of the modulatory actions of rHuEPO on the production and action of vasoregulatory factors and its direct and indirect effects on vascular function and structure.

Topics: Anemia, Iron-Deficiency; Animals; Endothelium, Vascular; Erythropoietin; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Recombinant Proteins; Renin-Angiotensin System; Risk Assessment; Sensitivity and Specificity; Vasoconstriction

Three intertwined issues--effectiveness, dosage, and route of administration--dominate discussion about recombinant human erythropoietin (rHuEPO). The major biological effect of rHuEPO is to regulate the number of committed erythroid precursors and to cause them to mature into erythrocytes. The constant presence of rHuEPO is critical to the sustenance, multiplication, and differentiation of committed erythroid progenitors that otherwise undergo apoptosis and die before they reach maturity. The route for rHuEPO administration influences the plasma concentration-time profiles. The erythropoietic response is not dependent on the peak concentration of rHuEPO achieved but on the duration of time that rHuEPO levels are maintained above a critical concentration. High levels immediately after intravenous doses are unnecessary to either induce or to sustain erythropoiesis. During the period of relative rHuEPO deficiency that invariably follows intravenous administration, committed but still rHuEPO-dependent cells undergo apoptosis and die in the bone marrow. The subcutaneous route sustains rHuEPO levels above basal levels in the interdialytic period, prevents death of rHuEPO-dependent cells, and results in more efficient and more sustained erythropoiesis. Areas under active investigation include modifications of the parent hormone and novel delivery systems that decrease elimination and maximize the residence time of rHuEPO in the circulation.

Topics: Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Male

Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (rHuEPO) that stimulates erythropoiesis by the same mechanism as the native hormone. The addition of two extra carbohydrate chains, however, gives NESP greater metabolic stability in vivo, and its terminal half-life after IV administration is three-fold longer than for IV rHuEPO. This allows injections of both IV and SC NESP to be given less frequently, and indeed studies have shown that once-weekly, and even once every other week, dosing can maintain the hemoglobin concentration in patients treated for renal anemia. The optimum starting dose is 0.45 microg/kg once weekly via the IV and SC routes of administration. Adverse effects are very similar to those seen with rHuEPO, and no antibodies have been detected in over 1,500 patients exposed to NESP thus far. NESP therefore represents a triumph for drug synthesis by recombinant DNA technology, and we can look to the future of this new therapeutic agent with much hope and expectation.

Topics: Anemia, Iron-Deficiency; Animals; Dogs; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Humans; Injections, Intravenous; Mice; Rats; Recombinant Proteins; Sensitivity and Specificity; Treatment Outcome

There is still controversy concerning the optimal target hemoglobin during treatment with recombinant human erythropoietin (rHuEPO). Some evidence suggests that hemoglobin concentrations higher than currently recommended lead to improvements in cognitive function, physical performance, and rehabilitation. At least in patients with advanced cardiac disease, however, one controlled trial failed to show a benefit from normalizing predialysis hemoglobin concentrations. In contrast, preliminary observations in three additional studies (albeit with limited statistical power) failed to show adverse cardiovascular effects from normalization of hemoglobin, but definite benefit with respect to quality of life, physical performance, and cardiac geometry. These observations are consistent with the notion that hemoglobin concentrations higher than those recommended by the National Kidney Foundation Dialysis Outcomes Quality Initiative Anemia Work Group are beneficial, at least in patients without advanced cardiac disease.

Topics: Anemia, Iron-Deficiency; Angina Pectoris; Controlled Clinical Trials as Topic; Erythropoietin; Female; Heart Function Tests; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Prognosis; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Increasing use of maintenance parenteral iron in the erythropoietin (EPO) era has been accompanied by growing concern about iron overload. This article attempts to put the issue of iron overload in hemodialysis patients into perspective. The condition is less common in all dialysis patients today than it was in the pre-EPO era, since fewer patients are being transfused and EPO therapy shifts iron into erythroid cells. Patients with end stage renal disease (ESRD) are less likely than patients with hemochromatosis to develop iron-induced organ dysfunction. Diagnosis of iron overload is best accomplished through liver biopsy. Clinically significant iron overload, which rarely occurs if ESRD patients are properly managed, can be treated in most EPO-treated renal failure patients by simply withholding parenteral iron therapy.

Topics: Anemia, Iron-Deficiency; Biopsy; Drug Monitoring; Erythropoietin; Ferritins; Hematinics; Hematocrit; Humans; Iron Overload; Kidney Failure, Chronic; Nursing Assessment; Practice Guidelines as Topic; Renal Dialysis; Risk Factors; Tissue Distribution; Transfusion Reaction

Alterations in [Hb], which are mediated through changes in arterial oxygen content, and alterations in BV, which are mediated through changes in cardiac output (Q), have a significant effect on both VO2max and aerobic performance. If BV is held constant, a decrease in [Hb] (anaemia) causes a decrease in VO2max and aerobic performance, while an increase in [Hb] (blood doping) causes an increase in VO2max and aerobic performance. If [Hb] is held constant, an increase in BV can cause and increase in both VO2max and aerobic performance, while a decrease in BV can cause a decrease in VO2max and aerobic performance. In addition, an increase in BV can compensate for moderate reductions in [Hb] through increase in Q, allowing VO2max to remain unchanged or even increase. Also, a large portion of the difference in the enhanced cardiovascular function of endurance athletes is due to their high BV and the resultant enhancement of diastolic function. Hence, optimizing both [Hb] and BV is a very important consideration for endurance performance.

Topics: Anemia, Iron-Deficiency; Blood Volume; Doping in Sports; Erythropoietin; Female; Hemoglobins; Humans; Male; Oxygen Consumption; Physical Endurance; Stroke Volume

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.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Intestinal Absorption; Iron; Iron Deficiencies; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Serum ferritin concentration is most informative in estimating the amount of storage iron available for a particular individual. The serum transferrin receptor concentration, in contrast to serum ferritin, provides direct information about any deficit in the adequacy of iron supply to the erythropoiesis. The combination of serum transferrin receptor and serum ferritin provides complete information about storage and functional iron compartments. Using this combination along with the hemoglobin concentration, it is possible to define the iron nutritional status completely. Inflammatory conditions as well as parenteral iron administration interfere, however, with the direct and quantitative ferritin to storage iron relationship and, therefore, have to be considered carefully with respect to diagnostic purposes. The diagnostic use of the serum transferrin receptor is presently limited because of limitations in methodology and definition (standardization) of reference ranges.

Topics: Anemia, Iron-Deficiency; Erythrocytes; Erythropoietin; Ferritins; Humans; Inflammation; Iron; Iron Deficiencies; Iron, Dietary; Receptors, Transferrin; Reference Values

The management of recombinant human erythropoietin (rHuEPO) treatment in hemodialysis patients requires close monitoring of iron status, because the pharmacologically stimulated erythropoiesis is particularly dependent on a continuous supply of iron. Parameters commonly measured to assess iron status are serum ferritin and the transferrin saturation. Both are indirect measures of iron availability for hemoglobin synthesis and frequently do not permit an assessment of the adequacy of iron supply to the erythron. Using flow cytometry, cell volume and hemoglobin concentration can be measured in individual red blood cells and reticulocytes. Based on these techniques, two parameters have proved to be particularly useful in identifying iron-deficient erythropoiesis. (a) The percentage of hypochromic erythrocytes (defined as red blood cells with a hemoglobin concentration of less than 28 g/dl) has been shown to detect insufficient marrow iron supply with a fairly good accuracy. (b) More recently, determination of the content of hemoglobin in reticulocytes (CHr) has been suggested by a number of authors to be even more sensitive in detecting iron-deficient erythropoiesis. For those who have access to an H*3 hematology analyzer, both indices can be determined at the time of a routine blood count at a minimal incremental cost.

Topics: Anemia, Iron-Deficiency; Erythrocyte Indices; Erythrocytes; Erythropoietin; Hemoglobins; Humans; Iron Deficiencies; Kidney Failure, Chronic; Phlebotomy; Recombinant Proteins; Renal Dialysis; Reticulocytes

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Blood Pressure; Coronary Disease; Drug Hypersensitivity; Erythropoietin; Humans; Injections, Intravenous; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Iron supplementation in pregnancy is a controversial issue. The aim of this review was to summarize the results of relevant papers on this subject.. Placebo-controlled studies on iron treatment in pregnancy were identified from the Cochrane database.. Among fertile women, 20% have iron reserves of >500 mg, which is the required minimum during pregnancy; 40% have iron stores of 100-500 mg, and 40% have virtually no iron stores. The demand for absorbed iron increases from 0.8 mg/day in early pregnancy to 7.5 mg/day in late pregnancy. Dietary iron intake in fertile women is median 9 mg/day, i.e. the majority of women have an intake below the estimated allowance of 12 18 mg/day. Iron absorption increases in pregnancy, but not enough to prevent iron deficiency anemia in 20%, of women not taking supplementary iron. Iron-treated pregnant women have greater iron reserves, higher hemoglobin levels, and a lower prevalence of iron deficiency anemia than placebo-treated women both in pregnancy as well as postpartum. Furthermore, children born to iron-treated mothers have higher serum ferritin levels than those born to placebo-treated mothers. An iron supplement of 65 mg/day from 20 weeks of gestation is adequate to prevent iron deficiency anemia.. In order to avoid iron deficiency in pregnancy, prophylactic iron supplement should be considered. Iron supplements may be administered on a general or selective basis. The selective approach implies screening with serum ferritin in early pregnancy, in order to identify women who can manage without prophylactic iron.

Topics: Adult; Anemia, Iron-Deficiency; Clinical Trials as Topic; Dietary Supplements; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Infant, Newborn; Iron, Dietary; Postpartum Period; Pregnancy; Pregnancy Complications; Prevalence; Receptors, Transferrin; Time Factors

While oral iron can be used to manage iron stores in some hemodialysis patients, most require intravenous iron supplementation. Maintenance of iron balance in these patients is critical, since patients with end stage renal disease often suffer from anemia caused by inadequate production of red blood cells and iron deficiency resulting from chronic blood loss. Using guidelines that include maintenance dosing ensures sustained adequate iron stores and maximizes the effects of rHuEPO therapy. Easy-to-administer clinical practice guidelines for repletion and maintenance of iron stores are presented here.

Topics: Algorithms; Anemia, Iron-Deficiency; Decision Trees; Drug Monitoring; Erythropoietin; Ferritins; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Nursing Assessment; Practice Guidelines as Topic; Renal Dialysis; Transferrin

Anemia is equally devastating in children as in adults. Decreased energy levels from anemia can lead to deterioration in the ability to (a) exercise, (b) participate in the normal activities of childhood, and (c) learn. Moreover, these effects may make it difficult for children to engage in social interactions with their peers, thereby altering their development. Epoetin alfa therapy effectively ameliorates the anemia of end-stage renal disease in pediatric dialysis patients and thus minimizes many of these negative effects. This article examines the use of Epoetin alfa in the pediatric population, including the role of nurses in educating patients and ensuring prescribed outcomes.

Topics: Adolescent; Age Factors; Anemia, Iron-Deficiency; Child; Energy Metabolism; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Patient Education as Topic; Play and Playthings; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Proper management of the anemia of end-stage renal disease (ESRD) requires chronic monitoring of an interrelated set of variables that can affect the erythrokinetic response. In most cases, therapeutic interventions should be determined on the basis of serial trends in laboratory values, thereby providing a historical pattern of clinical response. This article reviews the rationale for using laboratory trend analysis to manage anemia. A methodology for categorizing patterns in hemoglobin and hematocrit response to identify probable causes of hypo- or hyper-response to Epoetin alfa therapy is provided.

Topics: Anemia, Iron-Deficiency; Data Interpretation, Statistical; Drug Monitoring; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Middle Aged; Nursing Assessment

Anemia management using erythropoietin and intravenous iron supplementation has improved the lives of many patients with end stage renal disease (ESRD). However, because iron is an essential nutrient for microorganisms, it is plausible that iron supplementation may promote infection. This review examines the literature on the connection between iron and infection, with a focus on the relevance of these data to hemodialysis patients treated according to the National Kidney Foundation--Dialysis Outcomes Quality Initiative (NKF-DOQI) Guidelines for Anemia Management. The current evidence does not show a cause-and-effect relationship between intravenous iron administration and an increased susceptibility to infection in hemodialysis patients. Therefore, the author does not recommend changing current iron management practices in ESRD patients because of concern about infectious risk.

Topics: Anemia, Iron-Deficiency; Bacterial Infections; Erythropoietin; Evidence-Based Medicine; Humans; Iron Compounds; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis; Research Design; Risk Factors

Hyporesponse to Epoetin alfa therapy can be minimized by categorizing patients on the basis of trends in hemoglobin/hematocrit levels and initiating a continuous quality improvement effort that focuses on subnormal outcomes. An algorithm is provided that clinicians can use to proactively assess common causes that contribute to hyporesponse and limit the effect on patient outcomes.

Topics: Algorithms; Anemia, Iron-Deficiency; Decision Trees; Drug Monitoring; Erythropoietin; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Nursing Assessment; Quality of Life; Total Quality Management

At Winthrop-University Hospital, implementation of the National Kidney Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI) is guided by the principles of reengineering. On the basis of this model, anemia management is entrusted to a process owner. This advanced practice nurse is empowered with the responsibility of managing anemia and evaluated on his/her success in attaining predetermined quality standards-including ongoing patient satisfaction. This article examines use of the process owner position to evaluate, implement, and proactively manage anemia-related outcomes.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Renal Dialysis

One of the important components of successful anemia therapy in patients with end-stage renal disease (ESRD) treated with recombinant human erythropoietin is the maintenance of adequate available iron. To accomplish this task, iron status must be serially monitored and supplemental iron administered as required. Among nonuremic subjects, the body's iron supply is tightly conserved, and iron deficiency usually develops only when chronic blood loss occurs. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the body's storage of iron, and perhaps a deficit in intestinal iron absorption. Detecting iron deficiency in these patients can be difficult because of the inaccuracy of available diagnostic tests. The goals of iron therapy in ESRD include the prevention of iron deficiency by chronically supplementing iron, and the prompt treatment of overt iron deficiency. Oral iron supplements are inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit their effectiveness. Intravenous iron supplements have a greater efficacy then oral iron, which must be weighed against the small risk of allergic reactions. We present strategies for using the various diagnostic tests and treatment modalities to effectively manage iron supply for predialysis, hemodialysis, and peritoneal dialysis patients.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferritins; Humans; Iron; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Transferrin

Iron deficiency is common in patients with end stage renal disease (ESRD) receiving recombinant human erythropoietin (rHuEPO). Consequently, such patients require routine iron monitoring by measurement of serum ferritin and transferrin saturation, with interpretation of these values in light of the response to rHuEPO. This article will review issues related to iron metabolism, the causes and diagnosis of absolute and functional iron deficiency, and treatment options for iron deficiency. In addition, the role of the nurse in iron management will be identified.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Erythropoietin; Ferrous Compounds; Humans; Kidney Failure, Chronic; Nephrology; Specialties, Nursing

The data on the relationship between iron deficiency and infection are conflicting. Some researchers conclude that mild iron deficiency is beneficial for immunity, whereas others contend that any deficit is not good for immunity. Additionally, infection or inflammation generate anemia and profound changes in iron metabolism mediated by cytokines. These changes are important confounders to consider in assessments of iron status.

Topics: Anemia, Iron-Deficiency; Cytokines; Erythropoietin; Humans; Infections; Iron

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.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Ferritins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis

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.

Topics: Anemia, Iron-Deficiency; Citric Acid; Drug Combinations; Drug Monitoring; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Glucaric Acid; Humans; Infusions, Intravenous; Injections, Intravenous; Iron Compounds; Iron Overload; Iron-Dextran Complex; Kidney Failure, Chronic; Sorbitol

The management of anemia in dialysis patients involves a comprehensive understanding of the role of erythropoietin deficiency and of the importance of adequate available iron. It is clear that iron and recombinant human erythropoietin (rHuEPO) in concert allow the clinician to achieve a given target hematocrit in dialysis patients. By first repleting and then maintaining iron stores, and with an appreciation of the concept of functional iron deficiency, the nephrologist can achieve target hematocrits with the lowest necessary dose of rHuEPO. Iron repletion and maintenance is difficult to achieve with oral iron, and parenteral iron is needed in most cases. New protocols for ongoing parenteral maintenance therapy with iron dextran or iron gluconate, a form of iron likely to be available soon in the United States, should lead to achievement of target hematocrits in a greater number of patients and be cost-effective in improving patient outcomes.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Erythropoietin; Ferric Compounds; Hematinics; Hematocrit; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Practice Guidelines as Topic; Recombinant Proteins

Although iron deficiency is undoubtedly the commonest cause of anaemia even in elderly people, the aetiology is not always clear owing to various underlying diseases. Correction of anaemia is sometimes needed before surgery. The use of drugs that may influence blood coagulation, such as aspirin (acetylsalicylic acid), should be checked. Perioperative allogenic blood transfusion can often be avoided by the use of autologous blood and improved surgical techniques. Autologous blood donations are preferable in cases of planned surgery. Epoetin (recombinant human erythropoietin) in combination with iron supplementation facilitates the donation of autologous blood, even in elderly patients. Another method of avoiding allogenic blood transfusion is the collection and reuse of the blood a patient sheds in operations. During and/or after surgery, many haemostatic agents are available. Moreover, recent developments in gene engineering have enabled the utilisation of recombinant cytokines and coagulation factors. Further work remains to be done to define the proper use of these agents.

Topics: Aged; Aging; Anemia, Iron-Deficiency; Blood Transfusion; Blood Transfusion, Autologous; Erythropoietin; Geriatrics; Humans; Intraoperative Care; Preoperative Care

Patients receiving erythropoietin therapy require large quantities of iron to keep pace with the demands of the bone marrow during active erythropoiesis. If this iron supply to the marrow is not maintained, the response to erythropoietin is impaired, and indeed iron insufficiency is the most common cause of a poor response to this drug. Iron deficiency may be either absolute, which is defined as a reduction in total body iron stores, or functional, which implies adequate iron stores but a failure to supply available iron to the marrow or a failure in the utilization of this iron in the process of erythropoiesis. The detection of absolute or functional iron deficiency is difficult because there is no absolutely reliable marker of iron status, with the exception of an unequivocally low serum ferritin level. Measurement of serum ferritin and transferrin saturation are the most widely used methods, but both have drawbacks. Monitoring of the percentage of hypochromic erythrocytes in the circulation also seems promising, but the technology is of limited availability, and other methods (eg, monitoring erythrocyte ferritin, free erythrocyte protoporphyrin, and erythrocyte zinc protoporphyrin levels) lack widespread validation. Treatment of iron insufficiency is accomplished by intensifying iron supplementation either orally or intravenously, and in many instances the latter route becomes necessary. The high cost of erythropoietin demands that iron deficiency be screened for on a regular basis and treated to maximize the benefits of this drug.

Topics: Anemia, Iron-Deficiency; Biomarkers; Bone Marrow; Bone Marrow Cells; Erythropoiesis; Erythropoietin; Ferritins; Humans; Iron; Monitoring, Physiologic; Randomized Controlled Trials as Topic; Transferrin

In patients on chronic hemodialysis, there is no standard protocol for maintenance iron supplementation. This study aimed to compare two fixed-dose intravenous (IV) iron protocols to reduce erythropoiesis-stimulating agents (ESA). We conducted a double-blinded, randomized controlled study on hemodialysis patients having ferritin levels between 200 and 700 ng/dl and transferrin saturation values between 20 and 40%. Patients were assigned to receive either 100 or 200 mg of IV iron each month. ESA was adjusted every month to keep Hb between 10 and 12 g/dl. ESA dose at 12 months was the primary outcome. The secondary outcomes were all-cause mortality, cardiovascular events, absolute iron deficiency anemia (IDA), blood transfusion, adverse events, and iron withholding rate. Of the 79 eligible patients, 40 received 100 mg of IV iron, while 39 received 200 mg. At month 12, the mean monthly ESA dose in the 100-mg IV iron group was 35,706 ± 21,637 IU, compared to 26,382 ± 14,983 IU in the 200-mg group (P = 0.03). IDA was found in twelve patients (30%) in the 100-mg group and four patients (10.5%) in the 200-mg group (P = 0.05). In each group, three patients died (P = 0.9). Hospitalization, venous access thrombosis, and infection rates were similar in both groups. The withholding rate of IV iron was higher in 200-mg group (25% vs. 64.1%), but the protocol compliance was found more in 100-mg group (50% vs. 28.2%) (P = 0.001). In conclusion, monthly 200-mg IV iron infusions significantly reduce ESA doses but have a higher withholding rate. (Funded by the Kidney Foundation of Thailand and the Research Group in Nephrology and Renal Replacement Therapy from the Faculty of Medicine, Thammasat University).Thai Clinical Trials Registry number, TCTR20190707001.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Erythropoietin; Hematinics; Hemoglobins; Humans; Renal Dialysis

To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies.. Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum.. From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight.. Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.

Topics: Anemia, Iron-Deficiency; Birth Weight; Denmark; Dietary Supplements; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Infant, Newborn; Iron; Iron Deficiencies; Male; Placenta; Postpartum Period; Pregnancy

Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome.. In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289.. Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group.. An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery.. Vifor Pharma and Swiss Foundation for Anaesthesia Research.

Topics: Administration, Intravenous; Administration, Oral; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cardiac Surgical Procedures; Double-Blind Method; Drug Therapy, Combination; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Folic Acid; Heart Diseases; Humans; Male; Maltose; Middle Aged; Preoperative Care; Prospective Studies; Time Factors; Vitamin B 12

We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia.. Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia.

Topics: Adult; Anemia, Iron-Deficiency; Chronic Disease; Drug Therapy, Combination; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Iron; Pregnancy; Pregnancy Complications, Hematologic; Prospective Studies; Treatment Outcome

Antenatal iron and multiple micronutrient supplementation has been shown in randomized trials to improve birthweight, although mechanisms are unknown. We examined late pregnancy serum erythropoietin (EPO) and cortisol concentrations in relation to maternal micronutrient supplementation and iron status indicators (haemoglobin, serum ferritin, soluble transferrin receptor) in 737 rural Nepalese women to explore evidence of stress or anaemia-associated hypoxia. A double-masked randomized control trial was conducted from December 1998 to April 2001 in Sarlahi, Nepal, in which women received vitamin A alone (as control), or with folic acid (FA), FA + iron, FA + iron + zinc and a multiple micronutrient supplement. In a substudy, we collected maternal blood in the first and third trimester for biochemical assessments. Generalized estimating equations linear regression analysis was used to examine treatment group differences. EPO was ∼ 14-17 mIU mL(-1) lower (P < 0.0001) in late pregnancy in groups receiving iron vs. the control group, with no difference in the FA-only group. Cortisol was 1.3 μg dL(-1) lower (P = 0.04) only in the micronutrient supplement group compared with the control group. EPO was most strongly associated with iron status indicators in groups that did not receive iron, and in the non-iron groups cortisol was positively correlated with EPO (r = 0.15, P < 0.01) and soluble transferrin receptor (sTfR, r = 0.19, P < 0.001). In adjusted analyses, third trimester EPO was associated with a reduction in low birthweight, whereas cortisol was negatively associated with length of gestation and higher risk of preterm birth. Iron and multiple micronutrient supplementation may enhance birth outcomes by reducing mediators of maternal stress and impaired erythropoiesis.

Topics: Adult; Anemia, Iron-Deficiency; Biomarkers; Deficiency Diseases; Developing Countries; Dietary Supplements; Double-Blind Method; Erythropoietin; Female; Humans; Hydrocortisone; Iron, Dietary; Maternal Nutritional Physiological Phenomena; Micronutrients; Nepal; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third; Premature Birth; Risk; Rural Health; Young Adult

Gestational anemia increases the incidence of maternal and fetal complications. Adjuvant recombinant human erythropoietin (rHuEPO) has been used in patients who refuse blood transfusions, have a low response to treatment with iron sulfate, have limited time before birth, or have other illnesses that complicate the anemia. We demonstrated that the use of adjuvant rHuEPO with iron sulfate reduces the anemia time period and is innocuous to the fetus.. An experimental longitudinal prospective study; 100 pregnant women in their third trimester were included. Group 1 (n=50) was set as control for prevalence of anemia and establish hematological maternal and fetal parameters at delivery for our population; 50 women diagnosed with iron deficiency anemia were randomly assigned to treatment groups. Group 2 (n=25) third trimester women with a hemoglobin of <11g/dL were treated with iron sulfate, 600mg administered orally daily for 4 weeks, evaluating the hematologic response for the mother weekly and for both mother and fetus at birth; Group 3 (n=25) women similar to group 2, treated in addition with adjuvant rHuEPO, 4000 units subcutaneously, three times a week, for 4 weeks evaluating the same parameters.. Group 2 and 3 showed a corrected anemia before delivery (mean 11.1 vs 11.4g/dL), but Group 3 showed a statistically broader and more rapid increase in hemoglobin (1.22 vs 1.92g/dL, p value 0.013) with an rHuEPO dose of 4000 units, three times a week for 1 month. No clinical or hematologic difference or changes in growth were observed in the fetus.. Erythropoietin is safe and effective for both mother and fetus, although an ideal pregnancy dose has not yet been established.

Topics: Adult; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Humans; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Recombinant Proteins; Treatment Outcome

Randomized trials found that use of erythropoiesis-stimulating agents to target normal hematocrit (Hct) levels (>39%) compared with 27%-34.5% increases cardiovascular risk and mortality among chronic kidney disease patients. However, the effects of the most widely used Hct target in the past 2 decades, 34.5%-39%, have never been examined.. To compare the effects of 2 Hct target strategies-30.0%-34.5% (low) and 34.5%-39.0% (mid) in a high-risk population: elderly dialysis patients with significant comorbidities.. Observational data from the US Renal Data System were used to emulate a randomized trial in which patients were assigned to either Hct strategy. Follow-up started after completing 3 months of hemodialysis and ended 6 months later. We conducted the observational analogs of intention-to-treat and per-protocol analyses. Inverse-probability weighting was used to adjust for measured time-dependent confounding by indication.. A total of 22,474 elderly patients with both diabetes and cardiovascular disease who initiated hemodialysis in 2006-2008.. Hazard ratios (HRs) and survival probabilities for all-cause mortality and a composite cardiovascular and mortality endpoint.. The intention-to-treat HR (95% confidence interval) for mid versus low Hct strategy was 1.05 (0.99-1.11) for all-cause mortality and 1.03 (0.98-1.08) for the composite endpoint. The per-protocol HR (95% confidence interval) for mid versus low Hct strategy was 0.98 (0.78-1.24) for all-cause mortality and 1.00 (0.81-1.24) for the composite outcome.. Among hemodialysis patients, we did not find differences in 6-month survival or cardiovascular risk between clinical strategies that target Hct at 30.0%-34.5% versus 34.5%-39.0%.

Topics: Aged; Anemia, Iron-Deficiency; Cardiovascular Diseases; Comorbidity; Dose-Response Relationship, Drug; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Risk Factors; Survival Analysis; Treatment Outcome; United States

Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis.. We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6.. A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression.. FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Hepcidins; Humans; Inflammatory Bowel Diseases; Intercellular Signaling Peptides and Proteins; Male; Maltose; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Count; Prognosis; Prospective Studies; Thrombocytosis; Young Adult

Preliminary clinical evidence suggests that heme iron polypeptide (HIP) might represent a promising, novel oral iron supplementation strategy in chronic kidney disease. The aim of this multi-centre randomized controlled trial was to determine the ability of HIP administration to augment iron stores in darbepoetin (DPO)-treated patients compared with conventional oral iron supplementation.. Adult peritoneal dialysis (PD) patients treated with DPO were randomized 1:1 to receive two capsules daily of either HIP or ferrous sulphate per os for 6 months. The primary outcome measure was transferrin saturation (TSAT). Secondary outcomes comprised serum ferritin, haemoglobin, DPO dose and responsiveness, and adverse events.. Sixty-two patients were randomized to HIP (n = 32) or ferrous sulphate (n = 30). On intention-to-treat analysis, the median (inter-quartile range) TSAT was 22% (16-29) in the HIP group compared with 20% (17-26) in controls (P = 0.65). HIP treatment was not significantly associated with TSAT at 6 months on multivariable analysis (P = 0.95). Similar results were found on per-protocol analysis and subgroup analysis in iron-deficient patients. Serum ferritin levels at 6 months were significantly lower in the HIP group (P = 0.003), while the cost of HIP was 7-fold higher than that of ferrous sulphate. No other differences in secondary outcomes were observed.. HIP showed no clear safety or efficacy benefit in PD patients compared with conventional oral iron supplements. The reduction in serum ferritin levels and high costs associated with HIP therapy suggest that this agent is unlikely to have a significant role in iron supplementation in PD patients.

Topics: Administration, Oral; Adult; Aged; Anemia, Iron-Deficiency; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Peritoneal Dialysis; Treatment Outcome

The authors examined the impact of parenteral iron and recombinant human erythropoietin-β (rHuEPO-β) administered in the bilateral total knee replacement arthroplasty (TKRA), on postoperative anemia and transfusion requirements in iron-deficient patients.. A total of 108 iron-deficient patients were randomly assigned to two groups: Group C (control) or Group IE (200 mg of iron sucrose intravenously over 1 hr and 3000 IU of rHuEPO-β subcutaneously during the operation and during the postoperative period if the hemoglobin [Hb] level was 70-80 g/L). One or 2 units of blood were transfused to patients in both groups according to postoperative Hb level (between 60 and 70 g/L or betweeen 50 and 60 g/L, respectively). Perioperative laboratory and clinical outcomes (Hb, iron variables, postoperative bleeding amount, and number of units of RBCs transfused and incidences) were documented.. Although preoperative Hb and the amount of postoperative bleeding were comparable in the two groups, Hb levels at 1, 2, and 3 days and at 2 and 6 weeks postoperation were significantly higher in Group IE. Furthermore, the transfusion rate was significantly lower in Group IE (20.4% vs. 53.7%, p=0.011) and the mean number of red blood cell units transfused was markedly lower in Group IE (0.2±0.5 vs. 0.8±0.8, p=0.005). Postoperative iron, ferritin, and transferrin saturation levels were significantly higher in Group IE.. Treatment with parenteral iron and low-dose rHuEPO-β in bilateral TKRA effectively attenuated anemia and decreased transfusion requirements in iron-deficient patients.

Topics: Aged; Anemia, Iron-Deficiency; Arthroplasty, Replacement, Knee; Blood Transfusion; Erythropoietin; Humans; Iron; Postoperative Hemorrhage; Recombinant Proteins

Postpartum anemia is a common problem in obstetrics. Depending on the severity of anemia, it can cause a wide range of symptoms. Obstetrical management should be focused on avoiding blood transfusion in young and otherwise healthy women. The aim of this study was to examine the effectiveness of recombinant human erythropoietin (rhEPO) combined with iron sucrose compared to iron sucrose alone in patients with severe postpartum anemia.. A prospective randomized study was conducted in women with severe postpartum anemia (Hb < 8.5 g/dL). The first group received 200 mg iron sucrose intravenously daily on days 1-4. The second group received 200 mg iron sucrose plus 10.000E rhEPO in the same regimen. Twenty women were enrolled in each group. The follow-up period was two weeks.. Baseline Hb was 7.1 g/dL and 7.5 g/dL, respectively, depending on the subgroup. Hemoglobin values increased close to normal values within two weeks in both groups treated with iron sucrose alone or in combination with rhEPO (10.5 g/dL, 10.7 g/dL, respectively).. In general, iron sucrose alone is a sufficient anemia therapy agent. A subgroup of patients (i.e. with a more pronounced inflammatory response after cesarean section) may benefit from additional rhEPO therapy. Despite being severely anemic, none of our patients required transfusion. Iron sucrose as well as rhEPO was very well tolerated. The benefit of the therapy lies in the avoidance of allogenic blood transfusions with their potential side effects. In cases of severe anemia after operative delivery, additional rhEPO therapy can result in a faster Hb increase and, therefore, faster recovery.

Topics: Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Drug Administration Schedule; Drug Therapy, Combination; Erythrocyte Indices; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Interleukin-6; Pregnancy; Pregnancy Complications; Prospective Studies; Recombinant Proteins; Treatment Outcome

Intravenous (i.v.) iron sucrose similar (ISS) preparations are available but clinical comparisons with the originator iron sucrose (IS) are lacking.. The impact of switching from IS to ISS on anaemia and iron parameters was assessed in a sequential observational study comparing two periods of 27 weeks each in 75 stable haemodialysis (HD) patients receiving i.v. iron weekly and an i.v. erythropoiesis-stimulating agent (ESA) once every 2 weeks. Patients received IS in the first period (P1) and ISS in the second period (P2).. Mean haemoglobin value was 11.78 ± 0.99 g/dL during P1 and 11.48 ± 0.98 g/dL during P2 (P = 0.01). Mean serum ferritin was similar for both treatment periods (P1, 534 ± 328 μg/L; P2, 495 ± 280 μg/L, P = 0.25) but mean TSAT during P1 (49.3 ± 10.9%) was significantly higher than during P2 (24.5 ± 9.4%, P <0.0001). The mean dose of i.v. iron per patient per week was 45.58 ± 32.55 mg in P1 and 61.36 ± 30.98 mg in P2 (+34.6%), while the mean ESA dose was 0.58 ± 0.52 and 0.66 ± 0.64 μg/kg/week, respectively (+13.8%). Total mean anaemia drug costs increased in P2 by 11.9% compared to P1.. The switch from the originator IS to an ISS preparation led to destabilization of a well-controlled population of HD patients and incurred an increase in total anaemia drug costs. Prospective comparative clinical studies are required to prove that ISS are as efficacious and safe as the originator i.v. IS.

Topics: Anemia, Iron-Deficiency; Cohort Studies; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Prognosis; Renal Dialysis

Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent.. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG.. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%.. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Topics: Adult; Anemia, Iron-Deficiency; Drugs, Generic; Erythropoietin; Female; Ferric Compounds; Humans; Infusions, Intravenous; Male; Recombinant Proteins; Renal Dialysis; Sucrose; Sweetening Agents; Time Factors

The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status.. The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID).. We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed.. Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (±SD) concentration of 19.2 ± 2.5 ng/mL in the 2-mg/kg group compared with 13.0 ± 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status.. Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454.

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Dietary Supplements; Erythropoietin; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Iron; Iron Deficiencies; Male; Nutritional Status; Receptors, Transferrin; Reference Values; Trace Elements; Transferrin

Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.. Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953.. Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups.. Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.

Topics: Aged; Anemia, Iron-Deficiency; Chronic Disease; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Carriers; Erythropoietin; Female; Hematinics; Humans; Kidney Diseases; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy.. One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated.. More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter.. Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.

Topics: Aged; Anemia, Iron-Deficiency; Chronic Disease; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Renal Dialysis; Retrospective Studies; Survival Rate; Treatment Outcome

French and international clinical practice guidelines recommend a minimum hemoglobin level of 11 g/dl in patients with chronic kidney disease. Previous studies implemented between 1996 and 2003 showed that only 35 to 55% the patients reach this target. Dialysis NeoRecormon Epidemiology (DiaNE) is a one-year French multicentric observational study designed to follow a cohort of 1200 patients with ESRD treated with epoetin beta to assess the management of anemia in routine nephrologic practice. From December 2003 to September 2004, 1241 hemodialysis patients were recruited by 229 centers. At baseline, 64.4% of patients had hemoglobin levels greater than 11 g/dl. The proportion of patients with hemoglobin levels greater than 11 g/dl at the end of the study was 71.6%. These results could be partly explained by iron deficiency: 46% of patients had a serum ferritin between 200 and 500 microg/l and about one third of patients had a transferrin-iron saturation percentage greater or equal to 30% at baseline and at the end of the study. Epoetin beta was administrated by subcutaneous route in 65.5% of patients with similar efficacy and with less mean doses than intravenous route (114.6+/-81.5 IU/kg versus 146.5+/-124.3 IU/kg at the end of the study). In conclusion, the management of anemia in hemodialysis patients is not optimal but is slightly better than the management observed between 1996 and 2003. Iron and inflammatory status should be taken into account to improve the efficacy of anemia therapy using erythropoietin-stimulating agents.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Biomarkers; Comorbidity; Disease Management; Erythropoietin; Female; Follow-Up Studies; France; Humans; Inflammation; Injections, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Anemia is a common complication of inflammatory bowel disease (IBD) and iron deficiency (ID) is its predominant cause. Therefore, oral and intravenous iron replacements are widely used. This study was performed to evaluate the frequency and timing of anemia and ID recurrence after a successful treatment cycle.. Medical records of patients who had received iron sucrose with or without erythropoietin (EPO) in one of three prospective clinical trials that had been conducted at our center (Ann Intern Med 1997, Digestion 1999, and Am J Gastroenterol 2001) were analyzed for a 5-year follow-up period. The risk for recurrence of anemia (hemoglobin (Hb)<12/13 g per 100 ml) and ID (ferritin <30 microg/l) was evaluated by Kaplan-Meier analysis using the log-rank test.. Eighty-eight patients were available for analysis. Patients had received a mean iron dose of 2,500 mg (range 600-3,600 mg); 33 (37.1%) patients had also received EPO. Anemia recurred in a median of 10 months (95% confidence interval (CI) 8-12) and ID recurred within 19 months (95% CI 11-28). The iron dose had no influence on recurrence of ID or anemia. ID (but not anemia) recurred faster in patients with a post-treatment ferritin level <100 microg/l (median 4 months, 95% CI 1-7) than in patients with ferritin level between 100 and 400 microg/l (median 11 months, 95% CI 6-16) and >400 microg/l (median 49 months, 95% CI 32-66; P<0.001).. IBD-associated ID and anemia recur surprisingly fast, indicating that maintenance treatment may be needed in a portion of the patient population. Recurrence of ID (but not anemia) can be delayed by aiming for high post-treatment ferritin levels.

Topics: Adult; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Follow-Up Studies; Glucaric Acid; Hemoglobins; Humans; Inflammatory Bowel Diseases; Injections, Intravenous; Iron; Male; Prognosis; Prospective Studies; Recurrence; Treatment Outcome

Quantitative adjuvant zinc therapy using polaprezinc was performed to examine the correlation between zinc concentration and anemia in maintenance hemodialysis patients to propose appropriate treatment. Anemia and serum zinc concentration were measured in 117 patients with chronic renal failure receiving outpatient maintenance hemodialysis at Tsuyama Chuo Kinen Hospital. Two bags of polaprezinc (containing zinc 34 mg/day) were administered to 58 patients with lower than normal zinc levels (Zn < 80 mg/dl) as adjuvant zinc therapy to assess anemia improvement. Zinc concentration and all anemia parameters showed significant positive correlation, indicating that anemia improves in patients with high serum zinc levels. Regarding the effects of adjuvant zinc therapy for improving anemia, hemoglobin levels were found to increase significantly to the highest value at 3 weeks. During treatment, the dosage of erythropoietin was reduced significantly from baseline at all assessment points. No zinc poisoning from therapy was seen, but two patients had diarrhea (1.9%). Zinc-treated patients required iron therapy due to the development of iron deficiency. Most maintenance hemodialysis patients suffer from zinc deficiency anemia, and zinc-based polaprezinc has been confirmed to be an effective and safe adjuvant zinc treatment. Most patients diagnosed as refractory anemia with no response to erythropoietin also suffer from zinc deficiency anemia, many of whom are expected to benefit from zinc therapy to improve their anemia. Possible zinc deficiency anemia should be considered in the treatment of refractory anemia with no response to erythropoietin.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Carnosine; Diarrhea; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Iron Compounds; Japan; Kidney Failure, Chronic; Male; Middle Aged; Organometallic Compounds; Recombinant Proteins; Renal Dialysis; Zinc; Zinc Compounds

The use of poetam in the treatment of anemia in patients with dysfunctional uterine bleedings promotes recovery of the major parameters of the tone and reactivity of the autonomic nervous system.

Topics: Adolescent; Anemia, Iron-Deficiency; Antibodies; Autonomic Nervous System; Erythropoietin; Female; Humans; Metrorrhagia

Anaemia is a common in chronic kidney disease. Although erythropoietin and iron supplementation are established treatments, knowledge on the use of IV iron alone in patients not on dialysis or erythropoietin is incomplete. The responses of 82 patients referred to the renal anaemia service with haemoglobin of 11.5 g/dl or less were assessed 1 week after completing four once weekly doses of 200 mg of venofer. No patients were on dialysis or erythropoietin. The haemoglobin rise 1 week after treatment was 0.53 g/dl. Ferritin levels improved from 110.8 to 410.2 ng/l and transferrin saturation from 17.7 to 27.3%. Ferritin levels remained below our target range (200-500 ng/l) in 7.7% while 25.6% had levels above this. Ferritin levels remained less than 800 ng/l in nearly all patients. Intravenous iron is cost effective and should be considered for use in patients with renal anaemia. Patients with CKD stage 5 appeared to respond less well.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Drug Administration Schedule; Drug Monitoring; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glomerular Filtration Rate; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Severity of Illness Index; Sucrose; Transferrin; Treatment Outcome

Hepcidin is a key regulator of iron metabolism. In this study, we examined whether measurement of hepcidin is useful in assessing recombinant human erythropoietin (rHuEPO) responsiveness in regular hemodialysis (HD) patients in a cross-sectional fashion. We examined the association between serum prohepcidin, a prohormone of hepcidin, and rHuEPO dosage and the rHuEPO/hemoglobin (Hb) ratio in 75 HD patients. We also semiquantatively measured the peak intensity of serum hepcidin-25, the major form of mature hepcidin, in 24 HD patients by using surface-enhanced laser desorption ionization time of flight time mass spectrometry, and compared those between rHuEPO-hyporesponsive (rHuEPO 192 +/- 10 [126-252] IU/kg/week, n = 15) and responsive patients (rHuEPO 40 +/- 9 [0-81] U/kg/week, n = 9). A significant but weak relationship was found between serum prohepcidin and rHuEPO dosage (r = 0.24, p < 0.05) and rHuEPO/Hb ratio (r = 0.22, p = 0.06). However, prohepcidin did not become an indicator of hematopoietic parameters by multiple regression analysis. Serum hepcidin-25 intensity was significantly and positively correlated with ferritin (r = 0.51, p < 0.01) but not with log-transformed C-reactive protein. There was no difference in the intensities of serum hepcidin-25 between rHuEPO-hyporesponsive and responsive patients (64 +/- 10 vs. 52 +/- 16 AU, p = NS). It follows from these findings that the assessment of serum hepcidin using currently available assays was not valid in predicting rHuEPO responsiveness in chronic HD patients.

Topics: Aged; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Biomarkers; Cross-Sectional Studies; Drug Monitoring; Erythropoietin; Female; Ferritins; Hepcidins; Humans; Kidney Failure, Chronic; Male; Protein Precursors; Recombinant Proteins; Renal Dialysis; Reproducibility of Results

The percentage of hypochromic red blood cells (RBCs) (%HYPO) has been demonstrated as the best predictor of response to iron loading in haemodialysis patients treated with recombinant human erythropoietin (rHuEPO). However, we have previously shown that this parameter is positively influenced by erythropoietic activity since reticulocytes are considered hypochromic by cell counters. New cell counters are able to determine cell volume and haemoglobin (Hb) concentration separately on reticulocytes and mature erythrocytes. The aim of this study was to assess the sensitivity and specificity of mature erythrocyte parameters in detecting functional iron deficiency (FID).. A total of 32 stable chronic haemodialysis patients in the maintenance phase of rHuEPO therapy were included. Classical parameters of iron monitoring and mature erythrocyte parameters were measured after a 4-week iron-free period. Patients were classified as responders (R) or non-responders (NR) to an iron load of 100 mg iron sucrose at each dialysis session for 4 weeks, according to whether their Hb increased by >1 g/dl at the end of iron loading.. Twelve patients were identified as responders. Receiver operating characteristic (ROC) curve analysis demonstrated %HYPO and its corresponding parameter on mature erythrocyte, %HYPOm, as the best predictors of FID. The other parameters were ordered as follows: tranferrin saturation (TSAT), ferritin (FRT), mature RBC Hb content (CHm), mean corpuscular Hb concentration (MCHC), percentage of mature erythrocytes with a low CHm (%lowCHm), mean content in Hb (MCH) and reticulocyte Hb content CHr. Comparing the parameters at different cut-offs, the best sensitivity, specificity and efficiency were demonstrated for %HYPOm> 6%.. The best efficiency to predict FID was found for %HYPOm> 6%. The predictive value of %HYPO was quite similar. The clinical impact of %HYPOm in iron monitoring should also be tested in the induction phase of rHuEPO treatment because of its independence from erythropoietic activity.

Topics: Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biomarkers; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Renal Dialysis; Sensitivity and Specificity

Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients.. Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks.. At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner.. Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Anemia, Iron-Deficiency; Deoxyguanosine; DNA Damage; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Prospective Studies; Recombinant Proteins; Regression Analysis; Renal Dialysis

The aim of the study was to evaluate the role of hypochromic erythrocytes (HYPO%) compared to "traditional" and novel markers of iron status and erythropoiesis in recognizing iron-restricted erythropoiesis (IRE) and predicting response to erythropoietin (rHuEPO) in anemic patients with myeloma and lymphoma. Forty-one newly diagnosed patients who received epoetin-beta at a subcutaneous weekly dose of 30,000 IU for 6 weeks were studied. Response to rHuEPO was observed in 27 patients (65.8%). Twelve non-responders received, additionally, 200 mg of IV iron sucrose, weekly, for 4 weeks. Evaluation of markers was performed at baseline and on weeks 1, 2 and 6 for all patients and also on weeks 7-10 for non-responders to rHuEPO. Baseline HYPO%, at a cut-off value of <5%, and an increment in reticulocyte absolute number (RETICS-AB) >or= 50,000/microl and reticulocyte hematocrit (RETICS-Hct) >or= 50%, between baseline and week 2, were independent predictive factors for response to rHuEPO. We found that these markers had superior predictive value for response to rHuEPO than four widely used predictive models. Furthermore, a baseline HYPO% count of above 5% proved superior over serum ferritin < 100 ng/ml and transferrin saturation < 20% in recognizing IRE. In conclusion, baseline HYPO% either alone or in combination with RETICS-AB or RETICS-Hct after 2 weeks of rHuEPO treatment could be reliably used in predicting response to rHuEPO. Additionally, HYPO% has proved a reliable marker for recognizing IRE before rHuEPO treatment and, thus, could be used for identifying patients who will benefit from IV iron supplementation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Erythrocyte Indices; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematinics; Hematocrit; Humans; Lymphoma; Male; Middle Aged; Multiple Myeloma; Predictive Value of Tests; Recombinant Proteins

To study efficacy and safety of long-term administration of epoetin and iron preparations in glomerulonephritis (GN) patients with chronic kidney disease (CKD) of stage III-IV in systemic diseases.. A total of 189 patients at predialysis stage of CKD (glomerular filtration rate between 15 and 60 ml/min) were randomized into 3 groups depending on GN etiology: primary GN (group 1, 123 patients), GN in systemic diseases (group 2, 45 patients), controls (group 3, 21 patients). Anemia was characterized not only by red cells indices but also by the level of serum ferritin, C-reactive protein (CRP), saturation of transferrin with iron. Remodeling of the heart was determined in all the patients at dopplerechocardiography estimating left ventricular myocardial mass, relative thickness of its wall.. Correction of anemia was achieved in all the patients with GN and CKD of stage III-IV in systemic diseases despite the activity of systemic disease (high blood level of CRP) and persistent nephritis activity (high proteinuria). In many patients from groups 1 and 2 who were initially diagnosed to have left ventricular hypertrophy (LVH) of excentric type LVH regressed after 6 months of anemia correction. In group 3 with untreated anemia frequency of LVH increased.. Treatment of anemia in GN patients with CKD of stage III-IV in systemic diseases needed higher doses of epoetin and parenteral iron preparations compared to patients with the above stages of CKD with primary GN.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Disease Progression; Dose-Response Relationship, Drug; Echocardiography, Doppler; Epoetin Alfa; Erythropoietin; Female; Ferritins; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Iron Compounds; Kidney Failure, Chronic; Male; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Vitamin A deficiency impairs iron metabolism; vitamin A supplementation of vitamin A-deficient populations may reduce anemia. The mechanism of these effects is unclear. In vitro and in animal models, vitamin A treatment increases the production of erythropoietin (EPO), a stimulant of erythropoiesis.. We measured the effect of vitamin A supplementation on hemoglobin, iron status, and circulating EPO concentrations in children with poor iron and vitamin A status.. In a double-blind, randomized trial, Moroccan schoolchildren (n = 81) were given either vitamin A (200,000 IU) or placebo at baseline and at 5 mo. At baseline, 5 mo, and 10 mo, hemoglobin, indicators of iron and vitamin A status, and EPO were measured.. At baseline, 54% of children were anemic; 77% had low vitamin A status. In the vitamin A group at 10 mo, serum retinol improved significantly compared with the control group (P < 0.02). Vitamin A treatment increased mean hemoglobin by 7 g/L (P < 0.02) and reduced the prevalence of anemia from 54% to 38% (P < 0.01). Vitamin A treatment increased mean corpuscular volume (P < 0.001) and decreased serum transferrin receptor (P < 0.001), indicating improved iron-deficient erythropoiesis. Vitamin A decreased serum ferritin (P < 0.02), suggesting mobilization of hepatic iron stores. Calculated from the ratio of transferrin receptor to serum ferritin, overall body iron stores remained unchanged. In the vitamin A group at 10 mo, we observed an increase in EPO (P < 0.05) and a decrease in the slope of the regression line of log10(EPO) on hemoglobin (P < 0.01).. In children deficient in vitamin A and iron, vitamin A supplementation mobilizes iron from existing stores to support increased erythropoiesis, an effect likely mediated by increases in circulating EPO.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Dietary Supplements; Double-Blind Method; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Iron-Binding Proteins; Male; Morocco; Receptors, Cell Surface; Treatment Outcome; Vitamin A; Vitamin A Deficiency; Vitamins

To know the variations of serum transferrin receptor (sTfR) and its indices depending on the status of body iron and the presence of infection in children, to evaluate their usefulness for recognizing the nature of anemia in infection, and to know the role of erythropoietic activity in these conditions.. Three hundred and sixty-eight children between 1 and 10 years were included: 206 healthy children; 60 iron deficient anemic children (IDA); 102 with anemia and infectious disease, 58 of them meeting criteria for IDA. We measured hemoglobin, red cell indices, reticulocytes, transferrin saturation, serum ferritin, erythrocyte protoporphyrin, serum erythropoietin, and sTfR. Statistic method: ANOVA test, multiple linear regression, and ROC curve.. sTfR, sTfR/ferritin ratio, and sTfR-logferritin index values were found to increase significantly in IDA children. These values were significantly lower in infectious anemia than iron deficiency states. Serum erythropoietin only was elevated significantly in iron deficiency states. In children without infection, mean corpuscular hemoglobin, erythrocyte protoporphirin, erythropoietin logarithm, and total-iron-binding-capacity logarithm predicted 81% of sTfR variability. sTfR and its indices showed a very high sensitivity and specificity for recognizing iron deficiency states. In children with IDA and infection sensitivity for sTfR/ferritin ratio was low (area under the curve: 0.71; 95% confidence interval: 0.64-0.88). For discriminating the nature of anemia in infection the cut-off point obtained for sTfR, sTfR/ferritin ratio, and sTfR-F index were 3, 70, and 1.8, respectively, and their sensitivity and specificity were also very high.. sTfR, sTfR/ferritin ratio, and sTfR-F index are useful parameters for recognizing iron deficiency and the nature of anemia in infection. In IDA+infection, sTfR/ferritin ratio should not be recommended in the diagnosis of iron deficiency. In iron deficiency, erythropoietic activity has a secondary role as predictor factor of sTfR levels.

Topics: Anemia, Iron-Deficiency; Biomarkers; Child; Child, Preschool; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Infant; Infections; Male; Protoporphyrins; Receptors, Transferrin; Reticulocyte Count; Transferrin

Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents (ESA), randomized, controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis (PD) patients. In a multicenter trial, patients who had anemia, PD-dependent chronic kidney disease, stable ESA therapy, and a broad range of iron status (ferritin < or = 500 ng/ml, transferrin saturation < or = 25%) were randomly assigned to receive either 1 g of iron sucrose intravenously in three divided doses (300 mg over 1.5 h on days 1 and 15, 400 mg over 2.5 h on day 29) or no supplemental iron. No serious adverse drug events occurred after intravenous iron administration. The primary end point, peak hemoglobin increase, was higher (1.3 +/- 1.1 versus 0.7 +/- 1.1, mean +/- SD; P = 0.0028), and anemia intervention (transfusion, increase in ESA dose, or intravenous iron therapy not called for in protocol) occurred later (P = 0.0137) and less often in intravenous iron-treated patients compared with untreated control subjects (one of 66 [1.3%] versus five of 30 [16.7%]). Among patients who did not require intervention, iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects. Baseline iron status did not predict responsiveness to intravenous iron therapy. Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy.

Topics: Anemia, Iron-Deficiency; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins

Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis.. This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed.. Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration.. Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Confidence Intervals; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Risk Assessment; Severity of Illness Index; Treatment Outcome

Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) frequently develop anemia. Administration of recombinant human erythropoietin (rHuEPO) is effective in managing this anemia, although the additional demand for iron often results in iron deficiency. In adult patients undergoing HD, intravenous (IV) iron administration is known to replenish iron stores more effectively than oral iron administration. Nevertheless, IV iron supplementation is underutilized in pediatric patients, possibly because of unproved safety in this population. This international, multicenter study investigated the safety and efficacy of two dosing regimens (1.5 mg kg(-1) and 3.0 mg kg(-1)) of sodium ferric gluconate complex (SFGC) therapy, during eight consecutive HD sessions, in iron-deficient pediatric HD patients receiving concomitant rHuEPO therapy. Safety was evaluated in 66 patients and efficacy was evaluated in 56 patients. Significant increases from baseline were observed in both treatment groups 2 and 4 weeks after cessation of SFGC dosing for mean hemoglobin, hematocrit, transferrin saturation, serum ferritin, and reticulocyte hemoglobin content. Efficacy and safety profiles were comparable for 1.5 mg kg(-1) and 3.0 mg kg(-1) SFGC with no unexpected adverse events with either dose. Administration of SFGC was safe and efficacious in the pediatric HD population. Given the equivalent efficacy of the two doses, an initial dosing regimen of 1.5 mg kg(-1) is recommended for pediatric HD patients.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

To study the effect of infection on iron status in children suffering from acute, mild or severe respiratory infections and to determine the nature of anemia in infection using serum transferrin receptor (sTfR) levels.. Forty-three children aged between 3 and 5 y with no evidence of infection and receiving iron supplements in the preceding 100 days served as controls. Twenty-one children with mild upper respiratory infection and 94 children hospitalized for acute pneumonia constituted the experimental group. Hemoglobin (Hb), sTfR and serum ferritin were estimated in all the children at the time of diagnosis and again on the 15th and 30th days after the infection in those who were available for follow-up.. Mean (95% CI) sTfR was 6.08 (5.1-7.1) mg/l in healthy non-anemic children. Upper respiratory infection had no impact on Hb or sTfR but it significantly elevated serum ferritin levels. Eighty-three percent of the children with pneumonia had Hb less than 110 g/l at the time of diagnosis and had elevated mean sTfR, 18.0 (15.7-20.3) mg/l. There was a decline in mean sTfR by the 15th day of infection to 14.3 (11.3-17.4) mg/l with further rise to 22.9 (13.0-31.9) mg/l by 30 days. Serum ferritin was significantly elevated at the time of diagnosis (85.9; 71.1-100.8 micro g/l) as well as at 15 days (89.1; 68-110.1 micro g/l) with a decline by 30 days.. Severe lower respiratory infection exaggerates iron-deficient erythropoiesis by blocking release of iron from the storage pools. sTfR may not be a sensitive and specific tool of assessing true iron status of children exposed to severe infections.

Topics: Acute Disease; Anemia, Iron-Deficiency; Child, Preschool; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Pneumonia; Receptors, Transferrin; Respiratory Tract Infections; Time Factors

To investigate if oral use of Sorbifer Durules (EGIS Pharmaceutical Ltd, Budapest, Hungary) (1 tablet/d) is adequate for the maintenance of serum iron and vitamin C in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. One tablet of Sorbifer Durules contains 100 mg of Fe(2+) and 60 mg of vitamin C.. Short-term, open-label clinical trial.. Hemodialysis units.. Twenty-four adult patients with end-stage renal disease on hemodialysis.. Four-week treatment period of Sorbifer Durules, preceded and followed by iron and vitamin C washout periods.. Fasting predialysis serum samples were collected on days 0, 28, 56, and 84 to determine hematocrit, blood hemoglobin, serum iron, total iron-binding capacity, transferrin saturation, ferritin, vitamin C, and plasma oxalate.. Four-week treatment in hemodialyzed patients by Sorbifer Durules led to significant increase of hematocrit, blood hemoglobin, serum iron and vitamin C. This treatment did not influence the level of plasma oxalate.. Oral dose of one tablet of Sorbifer Durules per day is adequate for the maintenance of serum iron in normal range during recombinant human erythropoietin treatment in hemodialyzed patients. This treatment simultaneously prevented the development of serum vitamin C deficiency and did not lead to further increase of plasma oxalate in these patients.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Ascorbic Acid; Creatinine; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Recombinant Proteins; Renal Dialysis; Transferrin

Iron deficiency is a frequent cause of recombinant human erythropoietin (rhEPO)-resistant anemia in hemodialysis patients. Both reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) have been proposed as markers of iron deficiency, but it is unclear which parameter is superior.. To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency, we conducted a single-center, open-label, prospective, randomized, controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis. After 4 weeks of run-in period during which iron supplementation was suspended, 100 patients who were randomized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg, and 97 patients who were randomized to the TSAT group received the same doses of iron colloid when TSAT less than 20%. We measured the rhEPO dose needed to maintain prestudy hematocrit levels, hematocrit, CHr, TSAT, serum ferritin, percentage of hypochromic red blood cells, and total iron administered.. Sixteen weeks later, 94 patients in the CHr group and 89 patients in the TSAT group finished the study. The doses of rhEPO required decreased by 35.8% (4081 to 2629 U/week, P < 0.005) in the TSAT group, but not significantly in the CHr group (4121 to 3606 U/week). Although CHr increased promptly after the iron administration in both groups, TSAT increased only in the TSAT group.. Although CHr reflects the iron status more sensitively, TSAT is a better clinical marker for iron supplementation therapy.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Iron; Japan; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Reticulocytes; Transferrin

Malarial anemia is associated with a shift in iron distribution from functional to storage compartments. This suggests a relative deficit in erythropoietin production or action similar to that observed in other infections. Our study in Kenyan children with asymptomatic malaria aimed at investigating whether malaria causes increased erythropoiesis, and whether the erythropoietic response appeared appropriate for the degree of resulting anemia. Longitudinal and baseline data were used from a trial with a 2 x 2 factorial design, in which 328 anemic Kenyan children were randomly assigned to receive either iron or placebo, and sulfadoxine-pyrimethamine or placebo. Erythropoiesis was evaluated by serum concentrations of erythropoietin and soluble transferrin receptor. Prospectively collected data showed that malarial infection resulted in decreased hemoglobin concentrations, and increased serum concentrations of erythropoietin and transferrin receptor. Conversely, disappearance of malarial antigenemia resulted in increased hemoglobin concentrations, and decreased concentrations of these serum indicators. Additionally, our baseline data showed that current or recent malarial infection is associated with increased serum concentrations of erythropoietin and transferrin receptor, and that these were as high as or perhaps even higher than values of children without malarial infection and without inflammation. Our findings indicate that in asymptomatic malaria, the erythropoietic response is adequate for the degree of anemia, and that inflammation probably plays no or only a minor role in the pathogenesis of the resulting anemia. Further research is needed to demonstrate the role of deficient erythropoietin production or action in the pathogenesis of the anemia of symptomatic malaria.

Topics: Adaptation, Physiological; Anemia, Iron-Deficiency; Child, Preschool; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iron; Kenya; Longitudinal Studies; Malaria, Falciparum; Receptors, Transferrin

Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.

Topics: Adult; Anemia, Iron-Deficiency; Ascorbic Acid; Drug Resistance; Erythropoietin; Female; Hematopoiesis; Humans; Iron Overload; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Topics: Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

This study was undertaken to determine the efficacy and safety of intravenously administered iron sucrose with versus without adjuvant recombinant human erythropoietin in the treatment of gestational iron-deficiency anemia resistant to therapy with orally administered iron alone.. Forty patients with gestational iron-deficiency anemia were randomly assigned to receive intravenously iron sucrose plus recombinant human erythropoietin or iron sucrose alone twice weekly. Target hemoglobin value was 11.0 g/dL. Efficacy measures were reticulocyte count, increase in hematocrit, and time to target hemoglobin level (treatment duration in weeks and need for continued therapy after 4 weeks).. Both regimens were effective, but with adjuvant recombinant human erythropoietin the reticulocyte counts were higher from day 4 (P<.01), increases in hematocrit were greater from day 11 (P <.01), and the median duration of therapy was shorter (18 vs 25 days), with more patients reaching the target hemoglobin level by 4 weeks of treatment (n = 19 vs. n = 15). The groups did not differ with respect to maternal-fetal safety parameters.. Adjuvant recombinant human erythropoietin safely enhanced the efficacy of iron sucrose in the treatment of gestational iron-deficiency anemia resistant to orally administered iron alone.

Topics: Anemia, Iron-Deficiency; Erythrocyte Count; Erythrocyte Indices; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Fetal Growth Retardation; Glucaric Acid; Hematocrit; Humans; Placental Insufficiency; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Recombinant Proteins; Reticulocyte Count; Transferrin; Treatment Outcome; Ultrasonography

Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia.. One hundred three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity.. Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L.. Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.

Topics: Anemia, Iron-Deficiency; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Inflammatory Bowel Diseases; Interleukin-6; Logistic Models; Male; Prospective Studies; Receptors, Transferrin; ROC Curve; Sensitivity and Specificity; Transferrin; Treatment Outcome

To conduct a 3-month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage.. Thirty-five HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later.. In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 +/- 18 to 90 +/- 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05).. Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency.

Topics: Aged; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Topics: Anemia, Iron-Deficiency; Blood Pressure; Drug Hypersensitivity; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Injections, Intravenous; Iron-Dextran Complex; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8-7.2 mg/l to 10.5-11.3 mg/l.. In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Ferric Compounds; Ferrous Compounds; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Injections, Intramuscular; Iron; Recombinant Proteins; Regression Analysis; Statistics, Nonparametric; Time Factors

Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate.. Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 micrograms/dl and were then sustained for two additional months at 12 micrograms/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group).. Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean +/- SD) needed to maintain iron balance during month 6 was 56 +/- 37 mg in the i.v. iron group compared with 10 +/- 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 micrograms/dl dialysate iron. The incidence of adverse effects was similar in both groups.. Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Dialysis Solutions; Diphosphates; Drug Administration Routes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Solubility; Transferrin

Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second.. Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks.. During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl).. Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.

Topics: Adult; Anemia, Iron-Deficiency; C-Reactive Protein; Colitis, Ulcerative; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Glucocorticoids; Hemoglobins; Humans; Immunosuppressive Agents; Injections, Intravenous; Male; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

The administration of parenteral iron dextran to hemodialysis patients is typically intermittent. We sought to determine the most appropriate intervals for sampling iron parameters during intermittent need-based and continuous maintenance regimens and to quantify differences in efficacy between such regimens during long-term therapy. After a single course of 10 consecutive 100-mg iron doses administered to 14 patients on 16 occasions, transferrin saturation (TSAT) and ferritin were unreliable indices of iron status for the next 2 and 6 weeks, respectively. TSAT and ferritin levels at 1 week were virtually identical to those at 2 weeks after the administration of a single 50-mg or 100-mg iron dextran dose to 16 other patients. Twelve patients on maintenance iron therapy (25 to 100 mg/wk; TSAT, 30% to 50%) had a statistically significant decrease in the amount of recombinant human erythropoietin (rHuEPO) needed to maintain hemoglobin (Hb) levels between 10 and 11 g/dL compared with 12 patients receiving intermittent need-based dosing, an effect that persisted from week 16 to week 72 of the study. Maintenance iron was feasible even in a third group of eight patients targeted to sustain an Hb level of 14 g/dL. In both iron maintenance groups, iron indices could be measured at weekly intervals, and ferritin levels did not progressively increase over time. Continuous maintenance iron dextran used to maintain TSATs of 30% to 50% significantly reduced rHuEPO requirements and resulted in no adverse side effects in chronic hemodialysis patients. After weekly maintenance 25- to 100-mg iron dextran doses, iron indices can be measured after 1 week; a delay of 2 weeks is not necessary.

Topics: Aged; Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin

The use of erythropoietin (EPO) for the amelioration of anemia has dramatically changed the quality of life of the patients with chronic renal failure (CRF). The efficacy of a low dose EPO therapy was assessed in the prospective 6 week trial.. Assessment of hematological parameters and iron stores was done in 40 patients of CRF: Group A--20 patients of CRF receiving 40 U/kg EPO biweekly for 6 weeks and Group B--20 patients of CRF not receiving EPO. The parameters were studied at the start and at 2, 4 and 6 weeks of the study.. A statistically significant rise in mean haemoglobin levels (7.27 +/- 1.26 g/dl to 8.60 +/- 1.66 g/dl); mean packed cell volume (21.4 +/- 4.04% to 25.4 +/- 6.54%) and mean reticulocyte count (1.28 +/- 0.4% to 2.14 +/- 0.86%) was observed on EPO therapy. Patients on EPO developed a significant decline in serum iron, serum ferritin levels, bone marrow iron stores; and a hypochromic-microcytic picture on the peripheral blood film suggestive of iron deficiency. Iron deficiency at the start, chronic infections like tuberculosis and inadequate haemodialysis were identified as causes of hyporesponsiveness to EPO therapy. Low dose EPO therapy was not associated with any major adverse effects.. Low dose EPO (40 U/kg, biweekly) therapy is safe and effective in the management of anaemia of CRF.

Topics: Adult; Anemia, Iron-Deficiency; Blood Transfusion; Combined Modality Therapy; Erythropoietin; Female; Hematinics; Humans; Iron; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Prognosis; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Hemodialysis patients treated with recombinant human erythropoietin (rhEPO) need adequate iron supplementation to avoid rhEPO hyporesponsiveness due to iron deficiency. Low serum ferritin reflects absolute iron deficiency, whereas normal or high ferritin values in combination with low transferrin saturation (< 20%) indicate functional iron deficiency. In this study, healthy subjects (group I) were compared with intravenous (i.v.) rhEPO-treated and i.v. iron-saccharate-treated regular hemodialysis patients that were subdivided into three groups as follows: patients with serum ferritin > 100 and < 350 micrograms/L (group II), patients with ferritin < 60 micrograms/L (group III), and patients with ferritin > 650 micrograms/L but transferrin saturation < 20% (group IV). Polymorphonuclear leukocyte (PMNL) parameters (phagocytosis, intracellular killing of bacteria, oxidative metabolism, glucose uptake, intracellular calcium) for each group were compared with those of multitransfused, iron-overloaded primary hematologic patients (group V) and those of patients suffering from hereditary hemochromatosis (group VI). Compared with PMNL obtained from healthy subjects (group I), group II hemodialysis patients showed mild inhibition of phagocytosis but significant inhibition of intracellular killing of bacteria. Oxidative burst of PMNL from group II patients was also significantly reduced after stimulation in vitro. These dysfunctions were not affected by absolute iron deficiency (comparable data in group III patients). However, impairment of PMNL was markedly aggravated in group IV patients. Intracellular calcium concentration under basal conditions and after stimulation was not different. These data suggest that iron is responsible for the PMNL dysfunctions observed in group IV patients. The PMNL defect of group IV patients was comparable to group V and group VI patients with normal renal function, suggesting again a direct inhibitory effect of iron. It is concluded that hemodialysis patients with high ferritin but low serum iron and low transferrin saturation ("functional iron deficiency") display a significant impairment of fundamental PMNL functions during i.v. iron and rhEPO therapy. This may result in increased risk of infectious complications. Therefore, overtreatment of hemodialysis patients with i.v. iron should be avoided.

Topics: Adult; Aged; Analysis of Variance; Anemia, Iron-Deficiency; Blood Cell Count; Erythropoietin; Female; Ferritins; Humans; Injections, Intravenous; Iron Compounds; Kidney Failure, Chronic; Male; Middle Aged; Neutrophils; Prognosis; Recombinant Proteins; Renal Dialysis; Transferrin

The aim of this prospective study was to test a new protocol for iron supplementation in haemodialysis patients, as well as to assess the utility of different iron metabolism markers in common use and their 'target' values for the correction of iron deficiency.. Thirty-three of 56 chronic haemodialysis patients were selected for long-term (6 months) i.v. iron therapy at 20 mg three times per week post-dialysis based on the presence of at least one of the following iron metabolism markers: percentage of transferrin saturation (%TSAT) <20%; percentage of hypochromic erythrocytes (%HypoE) > 10% and serum ferritin (SF) <400 microg/l. Reasons for patient exclusion were active inflammatory or infectious diseases, haematological diseases, psychosis, probable iron overload (SF > or =400 microg/l) and/or acute need of blood transfusion mostly due to haemorrhage and change in renal replacement treatment.. More than half (51.8%) of the patients of our dialysis centre proved to have some degree of iron deficiency in spite of their regular oral iron supplementation. At the start of the study the mean haemoglobin was 10.8 g/dl and increased after the 6 months of iron treatment to 12.8 g/dl (P<0.0001). The use of erythropoietin decreased from 118 units/kg/week to 84 units/kg/week. The criterion for iron supplementation with the best sensitivity/specificity relationship (100/87.9%) was ferritin <400 microg/l. Patients with ferritin < 100 [microg/l and those with ferritin between 100 microg/l and 400 microg/l had the same increase in haemoglobin but other parameters of iron metabolism were different between the two groups.. Routine supplementation of iron in haemodialysis patients should be performed intravenously. Target ferritin values should be considered individually and the best mean haemoglobin values were achieved at 6 months with a mean ferritin of 456 microg/l (variation from to 919 microg/l). The percentage of transferrin saturation, percentage of hypochromic erythrocytes and ferritin <100 microg/l, were not considered useful parameters to monitor routine iron supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed.

Topics: Anemia, Iron-Deficiency; Biomarkers; Drug Administration Routes; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Follow-Up Studies; Glucaric Acid; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Support; Practice Guidelines as Topic; Prospective Studies; Recombinant Proteins; Renal Dialysis; Sucrose; Transferrin

To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1,800 g were randomly assigned to treatment group 1 (n = 15, receiving subcutaneous rhEpo 150 U/kg.time), treatment group 2 (n = 15, receiving 250 U/kg.time), three times a week for 6 weeks, and control group (n = 15, no treatment was given). All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P < 0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P < 0.0001 for all), but there was no significant difference between the two treatment groups (P > 0.05). Serum iron dropped significantly in the treatment groups as compared with control group (P < 0.01 for all), but no dose-dependent relationship was observed in treated infants (P > 0.05). After treatment, serum levels of erythropoietin was higher in group 2 than those in group 1 and control group (P < 0.0001, P < 0.01 and P < 0.05, respectively). There was no significant difference between group 1 and control group (P > 0.05). No side effects related to rhEpo therapy were observed. Our study suggested that rhEpo therapy stimulates endogenous erythropoiesis and enhances Ret, Hct and level of Hb in a dose-dependent manner in premature infants. The therapy is more efficient when given in higher dosages.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferrous Compounds; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Functional iron deficiency occurs when recombinant human erythropoietin (rHuEPO) accelerates erythropoiesis to an extent that the iron availability cannot meet the anticipated demand. Such a phenomenon will reduce the optimal response to rHuEPO. To estimate the iron needs of functional iron deficiency in hemodialysis patients on rHuEPO therapy, we utilized a mathematical method. Forty hemodialysis patients were examined in the study, and all had a baseline serum ferritin (SF) level > 100 microg/l. They were stratified into patients with a transferrin saturation (TfS) value > or = 25% (group I) and those below this value (group II). The treatment protocol consisted of rHuEPO therapy in the two groups for 6 months and iron supplement only in group II. The target hemoglobin level was 10.5 g/dl, and iron metabolism indices were analyzed prior to and following therapy. The results showed (1) in group I (n = 20) hemoglobin rose from 7.5 +/- 0.9 to 10.7 +/- 0.7 g/dl (p < 0.01) and the mean SF level declined from 1,583 +/- 997 to 968 +/- 664 mg (p < 0.01); (2) in group II (n = 20) hemoglobin also increased from 7.8 +/- 0.9 to 10.6 +/- 0.8 g/dl (p < 0.01) following iron supplement, while the SF rose from 183 +/- 70 to 326 +/- 125 mg (p < 0.01); (3) TfS was significantly elevated in group II following iron therapy (18.9 +/- 4.8 vs. 34.5 +/- 9.1%, p < 0.01), and (4) the nomogram showed a sensitivity of 80%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 83% in estimating the iron status before rHuEPO therapy. We conclude that SF levels reflect iron stores and that TfS < 25% is an index of functional iron deficiency. Iron supplementation is not necessary in patients with SF > 100 microg/l and TfS > or = 25%. It seems rational to provide intravenous iron in EPO-resistant patients with functional iron deficiency (SF > 100 microg/l, TfS < 25%). This paper illustrates the importance that accurate assessment of iron needs by a mathematical method would enhance treatment efficacy and avoid iron overload in hemodialysis patients on rHuEPO therapy.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Iron Overload; Kidney Failure, Chronic; Male; Mathematics; Middle Aged; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; Sensitivity and Specificity

Iron balance is critical for adequate erythropoiesis in hemodialysis patients treated with recombinant human erythropoietin (EPO). The role of oral iron therapy in maintaining or replenishing iron stores has not yet been well defined in such patients. We undertook a double-blind, placebo-controlled study to evaluate the efficacy of oral iron in 49 hemodialysis patients, divided into two groups, based on adequate or deficient iron stores. These groups were treated for 3 months with 150 mg elemental iron (Polysaccharide complex, Central Pharmaceuticals) or placebo, twice daily. Laboratory parameters were followed for five months. These parameters included: hematocrit (Hct), ferritin, transferrin saturation (Tsat), and zinc protoporphyrin (ZPP). A side-effects questionnaire was recorded monthly. Our results indicate that iron replete patients show evidence of falling iron stores during the study period; this observation was identical in both oral iron and placebo subgroups. Iron deficient patients had a significantly greater drop-out rate due to side effects when compared to iron replete patients (33% vs. 8%), despite equivalent responses to the side-effect questionnaire. We conclude: 1) Oral iron fails to maintain iron stores in iron replete patients; 2) Iron deficiency observed in this study may be due to poor medication compliance rather than side-effects.

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Double-Blind Method; Erythropoietin; Female; Ferritins; Follow-Up Studies; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Polysaccharides; Recombinant Proteins; Renal Dialysis; Time Factors

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Drug Administration Schedule; Erythropoietin; Female; Ferritins; Ferrous Compounds; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

We studied the effect of intravenous (i.v.) administration of 200 mg of iron sucrose following an i.v. bolus injection of recombinant human erythropoietin (r-HuEPO; 300 U/kg body weight) in seven subjects and compared it with seven subjects treated with r-HuEPO alone. Reticulocytes, serum erythropoietin (EPO) and ferritin levels were studied at baseline and daily for the following 8 d. Use of i.v. iron abolished the marked reduction in serum ferritin observed with r-HuEPO administration. Although the total number of reticulocytes was not affected by i.v. iron administration, the reticulocyte Hb content and retHb (a measure in g/l of the Hb contained in all reticulocytes) were increased in the i.v. iron/r-HuEPO group compared with the group who received r-HuEPO alone. Therefore i.v. iron significantly potentiates the haemopoietic response to r-HuEPO in normal subjects.

Topics: Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Iron; Male; Recombinant Proteins; Reticulocyte Count; Reticulocytes

Intravenous (IV) iron therapy can reduce erythropoietin (EPO) requirements in dialysis patients. Monitoring this response accurately is difficult. Estimation of red blood cell ferritin (RBCFer) and reticulocyte indices may give additional valuable information about iron availability to the erythroblasts (erythron). We evaluated the use of RBCFer, mean hemoglobin content of reticulocytes (CHr), and mean hemoglobin concentration of reticulocytes (CHCMr) in a prospective, nonblinded study of 22 hemodialysis patients (16 men and six women with a mean age of 62 years [range, 24 to 80 years]). All patients had an initial serum ferritin of < or = 60 microg/L. Patients with features known to produce EPO resistance and underlying bleeding/hematologic disorders were excluded. Patients were established on subcutaneous EPO and given IV iron therapy. The mean hemoglobin level remained constant throughout the study (P = 0.087). Serum ferritin and RBCFer increased significantly (P < 0.001 and 0.015, respectively) while a reduction in transferrin saturation became significant at the end of the study (P = 0.0047). A sharp increase in reticulocytes occurred in the first 14 days after commencement of IV iron, and there was an initial decrease in the percentage of hypochromic RBCs. An early decline in RBCFer was apparent. CHr increased with IV iron, indicative of increased iron supply to the developing erythron. Measurement of RBCFer and CHr provide evidence of increased iron supply for erythropoiesis during IV iron therapy. These measures help identify patients with functional iron deficiency and allow more accurate monitoring of response to IV iron therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biological Availability; Erythroblasts; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Erythropoiesis; Erythropoietin; Evaluation Studies as Topic; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Iron; Male; Middle Aged; Prospective Studies; Renal Dialysis; Reticulocytes

We sought to determine the rate and extent of iron utilization after administration of intravenous iron dextran and to compare the efficacy of iron dextran preparations of differing molecular weight. We randomized patients to receive either a 500-mg dose of iron dextran molecular weight (MW) 267,000 (group A) or iron dextran MW 96,000 (group B) administered in five sequential 100-mg doses, and examined indices of iron status before and at weekly intervals up to 4 weeks later. Although mean iron utilization was greater in the nine group A patients (46.7% +/- 21.3%) than in the 11 group B patients (31.7% +/- 26.6%), the difference was not statistically significant (P = 0.19). Iron utilization in both groups was substantially incomplete. Changes in serum ferritin and hemoglobin did not differ between the treatments (P = 0.49 and P = 0.34, respectively). We conclude that iron utilization after iron dextran administration is substantial within the first week after completing a course of therapy, associated with stable iron indices after the first 2 weeks, and incomplete for at least the first 4 weeks. Degree of iron utilization appears independent of molecular weight within the range we examined.

Topics: Anemia; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Intravenous; Iron; Iron Deficiencies; Iron-Dextran Complex; Male; Middle Aged; Molecular Weight; Prospective Studies; Recombinant Proteins; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Double-Blind Method; Erythropoietin; Humans; Inflammatory Bowel Diseases; Iron; Prospective Studies; Recombinant Proteins

We have compared the efficacy of oral to intravenous iron for the chronic maintenance of iron stores in hemodialysis patients. Fifty-two hemodialysis patients with initial serum ferritin greater than 100 ng/mL and transferrin saturation greater than 15% were randomly assigned to one of two groups: those receiving oral iron therapy (n = 32) and those receiving intravenous iron dextran (100 mg twice weekly) (n = 20). At study completion (4 months), the mean hematocrit was significantly higher in the intravenous group than in the oral iron group (34.4% +/- 0.7% v 31.8% +/- 0.4%, respectively; P < 0.05), the final mean recombinant human erythropoietin dose was 46% lower in the intravenous iron group than in the oral group (4,050 +/- 634 U/treatment v 7,563 +/- 378 U/treatment; P < 0.05), and the mean serum ferritin was significantly higher in the intravenous group than in the oral iron group (753.9 +/- 30.2 ng/mL v 157.3 +/- 15.4 ng/mL, respectively; P < 0.05). We have found that administering iron intravenously instead of orally for chronic maintenance iron supplementation in hemodialysis patients resulted in improved erythropoiesis. We hypothesize that most hemodialysis patients have inadequate iron stores for optimal erythropoiesis when currently recommended levels of ferritin and transferrin saturation are used to guide therapy, and that the chronic use of intravenous iron could reduce recombinant human erythropoietin requirements by maximizing iron stores. The improvement in erythropoiesis was accompanied, however, by an increase in iron indices to levels that could be indicative of tissue iron overload. Future studies must be performed to determine whether lower doses of intravenous iron dextran would improve erythropoiesis without causing potential organ iron overload.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

A prospective study with 65 maintenance hemodialysis (MHD) patients on recombinant human erythropoietin (rHuEPO) therapy was conducted to assess the effect of iron balance on responsiveness. An attempt to define the predictors of erythropoietin (EPO) response and identify the specific causes of EPO resistance was undertaken in the present study. The treatment protocol consisted of two stages, the first was rHuEPO therapy for 6 months and the second was iron supplementation plus rHuEPO therapy in patients without response to EPO for the next 6 months. According to the hemoglobin (Hb) changes (increment exceeded 30% of baseline or did not exceed 15% of baseline for 3 consecutive months) and whether or not there was an achievement of target Hb level (>10.5 g/dl), all patients (n = 65) were divided into EPO-responsive (n = 20) and EPO-resistant (n = 45) groups. The EPO-resistant patients were then further stratified into iron-responsive (n = 29) and iron-irresponsive (n=16) groups. Iron metabolism and red cell indices were analyzed prior to and following rHuEPO therapy and iron supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anemia; Anemia, Iron-Deficiency; Drug Resistance; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

In a double-blind, randomised study we treated 36 women in the puerperium with haemoglobin concentration below 9 g/dl with 400 mg Fe . 20 women received 20,000 IE erythropoietin (rHuEPO) i.v. in addition, 12 women received placebos. In both groups there were no differences in the haematological and iron parameters in the first 4 weeks after delivery. The results show that the additional therapy with rHuEPO in postpartum anaemia is not justified. The limiting factor in a quick correction of the postpartum anaemia is the insufficient presence of iron at the end of pregnancy. The therapy of choice for quick and safe correction of p.p. anaemia is the effective intravenous iron supplementation.

Topics: Anemia, Iron-Deficiency; Combined Modality Therapy; Double-Blind Method; Erythrocyte Count; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobinometry; Humans; Infusions, Intravenous; Iron; Prospective Studies; Puerperal Disorders; Recombinant Proteins

Iron supplementation is required by most dialysis patients receiving recombinant human erythropoietin. The efficacy of oral iron is variable in these patients, and many require the use of intravenous iron dextran to maintain adequate iron levels, defined as transferrin saturation greater than 20%, serum ferritin greater than 100 ng/mL, and serum iron greater than 80 micrograms/dL. To determine the efficacy of different oral iron preparations in maintenance of iron status, we prospectively studied 46 recombinant human erythropoietin-treated patients and randomized them to receive different oral iron preparations. These four preparations included Chromagen (ferrous fumarate; Savage Laboratories, Melville, NY), Feosol (ferrous sulfate; SmithKline Beecham, Inc, Pittsburgh, PA), Niferex (polysaccharide; Central Pharmaceuticals, Inc, Seymour, IN), or Tabron (ferrous fumarate; Parke-Davis, Morris Plains, NJ). All patients were prescribed approximately 200 mg of elemental iron daily of their assigned iron preparation with at least 100 mg ascorbic acid daily for 6 months. At baseline and bimonthly during the study, serum iron, transferrin saturation, ferritin, hematocrit, and recombinant human erythropoietin dose were monitored; in addition, compliance and side effects were recorded by patient interview. All patients were able to maintain target hematocrit during the 6 months of study. However, there were differences in the trends of serum iron, percent transferrin saturation, and ferritin when considered singly or in combination between the four groups of iron medications. The percent of laboratory values measured over the study period in each group that met the criteria of transferrin saturation more than 20% was greatest in the Tabron group (58%), followed by the Feosol (47%), Chromagen (33%), and Niferex (31%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Erythropoietin; Female; Ferrous Compounds; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Compliance; Polysaccharides; Prospective Studies; Recombinant Proteins; Renal Dialysis

The aim of this study was to determine whether the preoperative administration of recombinant human erythropoietin (rHuEPO) could increase the rate of autologous blood donation and reduce the perioperative need for homologous blood in anaemic patients with cancer. Twenty-two anaemic (haematocrit less than 34 per cent), iron-deficient (iron less than 700 micrograms/l) patients, with gastric or colorectal cancer scheduled for elective surgery, were allocated randomly to two groups. The first (n = 11) received iron saccharate 200 mg/day intravenously for 12 consecutive days. The second (n = 11) received rHuEPO subcutaneously (300 units/kg as first administration, and 100 units/kg 4, 8 and 12 days later) with supplemental iron. On days 4, 8 and 12, if the haematocrit was greater than 34 per cent, patients donated one unit (350 ml) of autologous blood. In the iron group the mean haematocrit did not change from admission (31 per cent) to day 12 of treatment (31 per cent), and no patient could donate autologous blood. In the rHuEPO group, eight patients donated two units of autologous blood and three donated one unit. Four patients in the iron group received perioperative transfusion of homologous blood compared with none in the rHuEPO group. Administration of rHuEPO facilitated the donation of autologous blood and reduced perioperative homologous blood transfusion in anaemic patients with cancer.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Blood Transfusion, Autologous; Colonic Neoplasms; Erythropoietin; Female; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Recombinant Proteins; Rectal Neoplasms; Stomach Neoplasms

Treatment of renal anemia with recombinant human erythropoietin (rEPO) frequently raises arterial blood pressure. The objective of this study was to determine whether this is a direct effect of rEPO or a consequence of the expansion of erythrocyte mass. Twenty-three chronic hemodialysis patients receiving maintenance rEPO therapy who had uncontrolled anemia due to iron deficiency were studied. It was anticipated that repletion of iron stores with iv iron dextran would restore rEPO responsiveness, leading to a gradual rise in hematocrit to the target values (0.30 to 0.33). The effect of the increase in hematocrit on arterial blood pressure could then be dissected from the direct effect of rEPO in patients receiving constant doses of rEPO throughout the study period. To this end, arterial blood pressure, iron indices, hematocrit, and measures of fluid balance were monitored at baseline and for a 10-wk period after iron repletion. In eight patients, the hematocrit transiently rose above 0.33, triggering a reduction in rEPO dosage. In the remaining 15 patients, rEPO dosage was held constant during the study period. In this subgroup, repletion of iron stores led to a rise in hematocrit from 0.25 +/- 0.04 to 0.32 +/- 0.04 (P < 0.001) within 4 wk. Despite the significant rise in hematocrit, both systolic and diastolic blood pressure values remained virtually unchanged. Likewise, body weight and interdialytic fluid gain were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia, Iron-Deficiency; Blood Pressure; Erythropoietin; Female; Hematocrit; Humans; Hypertension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Anemia does not correct in many kidney transplant recipients, probably due to iron deficiency or inadequate erythropoietin (Epo) production. We evaluated effects of iron (Fe) availability on correction of anemia in renal transplant recipients and sought to characterize patterns of early Epo production by transplanted kidneys as related to peritransplant factors. In a prospective randomized trial, 51 consecutive renal transplant patients were followed for 6 months. Epo was measured on days 0, 3, 14, 48 and 168 posttransplantation. Fe status was monitored on days 14, 48 and 168. Pts were randomized at day 14 based on Fe status. Iron-deficient (FeD) patients (n = 24) were randomized to receive daily Fe supplementation (FeDs, n = 12) or no supplementation (FeDns, n = 12). Those with normal Fe status (FeN, n = 27) were followed as controls. No differences were found between groups at day 0 for Hct, Cr, Epo, age, dialysis history, or type of donor. Day 3 Creatinine and Hct were similar among groups, while Epo was significantly higher in FeD groups vs FeN (p < 0.004), and continued higher at 6 months. Though each pt improved Hct, most FeDns and FeN were anemic and Fe deficient at 6 months while all FeDs patients had corrected their anemia (p < or = 0.009) and Fe status. Four FeDs patients developed polycythemia. Epo production correlated inversely to cold ischemia time in cadaver renal allografts (p < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anemia, Iron-Deficiency; Creatinine; Erythropoietin; Female; Ferritins; Ferrous Compounds; Follow-Up Studies; Humans; Immunosuppressive Agents; Iron; Kidney Transplantation; Male; Prospective Studies; Time Factors; Transferrin

Topics: Anemia, Iron-Deficiency; Erythropoietin; Hemoglobins; Humans; Iron; Iron Deficiencies; Renal Dialysis; Serum Albumin; Transferrin

Iron deficiency is a potent stimulator of fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism, that is classically thought to be produced by bone-embedded osteocytes. Here, we show that iron-deficient transmembrane serine protease 6 knockout (Tmprss6-/-) mice exhibit elevated circulating FGF23 and Fgf23 messenger RNA (mRNA) upregulation in the bone marrow (BM) but not the cortical bone. To clarify sites of Fgf23 promoter activity in Tmprss6-/- mice, we introduced a heterozygous enhanced green fluorescent protein (eGFP) reporter allele at the endogenous Fgf23 locus. Heterozygous Fgf23 disruption did not alter the severity of systemic iron deficiency or anemia in the Tmprss6-/- mice. Tmprss6-/-Fgf23+/eGFP mice showed green fluorescence in the vascular regions of BM sections and showed a subset of BM endothelial cells that were GFPbright by flow cytometry. Mining of transcriptomic data sets from mice with normal iron balance revealed higher Fgf23 mRNA in BM sinusoidal endothelial cells (BM-SECs) than that in other BM endothelial cell populations. Anti-GFP immunohistochemistry of fixed BM sections from Tmprss6-/-Fgf23+/eGFP mice revealed GFP expression in BM-SECs, which was more intense than in nonanemic controls. In addition, in mice with intact Tmprss6 alleles, Fgf23-eGFP reporter expression increased in BM-SECs following large-volume phlebotomy and also following erythropoietin treatment both ex vivo and in vivo. Collectively, our results identified BM-SECs as a novel site for Fgf23 upregulation in both acute and chronic anemia. Given the elevated serum erythropoietin in both anemic models, our findings raise the possibility that erythropoietin may act directly on BM-SECs to promote FGF23 production during anemia.

Topics: Anemia, Iron-Deficiency; Animals; Bone Marrow; Disease Models, Animal; Endothelial Cells; Erythropoietin; Iron; Mice; RNA, Messenger; Up-Regulation

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Celiac Disease; Child; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Hepcidins; Humans; Infections; Inflammatory Bowel Diseases; Iron; Male; Receptors, Transferrin; Transferrin; Vitamin B 12

Early and adequate correction of the anemic syndrome (AS) of cancer patients can prevent deterioration in the quality of life and be considered as a reserve for increasing the effectiveness of treatment for breast cancer (BC). The aim of the study was to assess the status of iron using modern methods of ferrokinetics in breast cancer patients on the background of adjuvant chemotherapy for early diagnosis and adequate treatment of AS. The object of the study included 21 breast cancer patients with a relatively favorable prognosis, with luminal types A and B (Her 2 / neu positive or negative), three times negative type. The examination was carried out in the postoperative period, against the background of adjuvant chemotherapy. The main metabolites of ferrokinetics were studied: hepcidin 25 (GP25); ferritin (FR); soluble transferrin receptors (rRTP); transferin (TRF); iron (Fe); erythropoietin (EPO); CRP and IL-6 indicators. AC correction was performed (ferinject, epotin-alpha, B12). 10 (47.6%) patients with breast cancer had AS. Most of them were diagnosed with IDA with microcytic, hypochromic characteristics of erythrocytes, low concentration of FR, Fe, GP25, IL-6, CRP, and high levels of TRP and rRTP. Functional iron deficiency (FDF) was established in some patients. In contrast to patients with IDA, they had a high concentration of FR, CRP and significant production of GP25, IL-6. The EPO level was not optimal for the majority of patients with AS. In isolated cases, during treatment with recombinant erythropoietins, a deficiency of vitamin B12 (cyanocobalamin) was revealed. The rational use of iron preparations, vitamins, and recombinant forms of EPO made it possible to restore Fe metabolism, stabilize the hemoglobin level, and also improve the condition of most breast cancer patients. The obtained data on IL-6, GP25, CRP indicate a certain relationship between them in the development of anemia with VDF in breast cancer patients and the need for further study of the characteristics of iron metabolism in cancer patients.

Topics: Anemia; Anemia, Iron-Deficiency; Breast Neoplasms; Chemotherapy, Adjuvant; Erythropoietin; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Interleukin-6; Iron; Quality of Life

While elevated hepcidin levels with inflammation have been postulated as a putative mechanism hindering effective erythropoiesis after intravenous (IV) iron therapy in anemic patients undergoing surgery, little is known about the concomitant changes in other major regulators affecting erythropoiesis. This study investigated the activities of relevant regulators after iron replenishment in a rat model of iron deficiency anemia with inflammation.. Inflammation was induced by administration of complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. After 2 weeks of CFA treatment, the rats received IV iron (CFA‑iron) or saline (CFA-saline). The control group received saline instead of CFA and iron (saline-saline). At 1, 3, and 10 days after iron or saline treatment, inflammatory cytokines, oxidative markers, iron profiles, hepcidin, erythropoietin (EPO), erythroferrone (ERFE), fibroblast growth factor 23 (FGF 23), and expression of mRNA and proteins in the liver involved in hepcidin signaling pathways were measured.. CFA treatment and iron restriction decreased hemoglobin and serum iron levels, significantly increasing inflammatory and oxidative markers. Iron supplementation did not restore hemoglobin levels despite improved iron profiles. CFA injections increased hepcidin and FGF 23 levels and decreased EPO and ERFE levels, which further intensified after iron supplementation with concomitantly elevated levels of oxidative stress and inflammatory markers.. Under inflammatory conditions, IV iron administration exacerbated inflammatory and oxidative stress and did not resolve anemia, even under iron deficiency conditions. Iron therapy exerted adverse influences on the changes in key regulators toward impeding erythropoiesis that was already impeded by inflammation.

Topics: Anemia; Anemia, Iron-Deficiency; Animals; Biomarkers; Dietary Supplements; Erythropoiesis; Erythropoietin; Hemoglobins; Hepcidins; Inflammation; Iron; Iron Deficiencies; Male; Rats; Rats, Sprague-Dawley

Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants.. Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined.. Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy.. During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron; Reticulocytes; Retrospective Studies

Anemia is defined as a low red blood cell count, a low hematocrit, or a low hemoglobin concentration. In pregnancy, a hemoglobin concentration of less than 11.0 g/dL in the first trimester and less than 10.5 or 11.0 g/dL in the second or third trimester (depending on the guideline used) is considered anemia. Anemia is the most common hematologic abnormality in pregnancy. Maternal anemia is associated with adverse fetal, neonatal and childhood outcomes, but causality is not established. Maternal anemia increases the likelihood of transfusion at delivery. Besides hemodilution, iron deficiency is the most common cause of anemia in pregnancy. The American College of Obstetricians and Gynecologists recommends screening for anemia with a complete blood count in the first trimester and again at 24 0/7 to 28 6/7 weeks of gestation. Mild anemia, with a hemoglobin of 10.0 g/dL or higher and a mildly low or normal mean corpuscular volume (MCV) is likely iron deficiency anemia. A trial of oral iron can be both diagnostic and therapeutic. Mild anemia with a very low MCV, macrocytic anemia, moderate anemia (hemoglobin 7.0-9.9 g/dL) or severe anemia (hemoglobin 4.0-6.9 g/dL) requires further investigation. Once a diagnosis of iron deficiency anemia is confirmed, first-line treatment is oral iron. New evidence suggests that intermittent dosing is as effective as daily or twice-daily dosing with fewer side effects. For patients with iron deficiency anemia who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred. With contemporary formulations, allergic reactions are rare.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Blood Transfusion; Child; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Infant, Newborn; Iron; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Pregnancy Trimesters

Anemia with inflammation-induced defective iron utilization is a pathological condition observed in patients suffering from chronic kidney disease (CKD) or chronic inflammatory disease. There is no reasonable treatment for these conditions, because the effects of erythropoiesis stimulating agents (ESAs) or iron supplementation in the treatment of anemia are insufficient. JTZ-951 (enarodustat) has been characterized as a novel, orally bioavailable inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), and has been developed as a novel therapeutic agent for anemia with CKD. In this study, the effects of JTZ-951 on iron utilization during erythropoiesis and on anemia of inflammation were compared with those of recombinant human erythropoietin (rHuEPO) using normal rat and rat model of anemia of inflammation. In normal rats, under conditions in which JTZ-951 and rHuEPO showed similar erythropoietic effect, repeated doses of JTZ-951 induced erythropoiesis while retaining the hemoglobin content in red blood cells, while administration of rHuEPO resulted in decrease in some erythrocyte-related parameters. As for iron-related parameters during erythropoiesis, JTZ-951 exhibited more efficient iron utilization compared to rHuEPO. A single dose of JTZ-951 resulted in decrease in hepcidin expression observed within 24 h after administration, but a single dose of rHuEPO did not. In a rat model of anemia of inflammation (also known as a model with functional iron-deficiency), JTZ-951 showed erythropoietic effect, in contrast with rHuEPO. These results suggest that, unlike rHuEPO, JTZ-951 stimulates erythropoiesis by increasing iron utilization, and improves anemia of inflammation.

Topics: Anemia, Iron-Deficiency; Animals; Arthritis, Experimental; Biomarkers; Enzyme Inhibitors; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematinics; Hepcidins; Hypoxia-Inducible Factor-Proline Dioxygenases; Iron; N-substituted Glycines; Pyridines; Rats, Inbred Lew; Recombinant Proteins; Triazoles

Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality.. We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin <100 µg/L or 100-299 µg/L with transferrin saturation <20%. EPO-resistant patients (22%) had more advanced HF whereas those with EPO deficiency (57%) were more frequently females and had worse renal function. Lower serum ferritin (indicating depleted body iron stores) was related to higher EPO observed/predicted ratio when adjusted for significant clinical confounders, including C-reactive protein. One year all-cause mortality was 28% in patients with EPO resistance compared to 17% in patients with EPO deficiency and 10% in patients with adequate EPO (log-rank test for the comparison EPO resistance vs. adequate EPO: P = 0.02). When adjusted for other prognosticators, there was still a trend towards increased 12-month mortality in patients with higher EPO level.. Anaemic HF patients with endogenous EPO deficiency vs. resistance have different clinical and laboratory characteristics. In such patients, ID contributes to EPO resistance independently of inflammation.

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Iron Deficiencies; Male; Middle Aged

Our previous randomized controlled trial comparing the total dose of weekly versus biweekly continuous erythropoietin receptor activator (CERA) therapy to maintain optimal hemoglobin (Hb) levels showed no significant differences between the two therapies. This post-hoc analysis assessed whether the total dose of weekly versus biweekly CERA therapy to maintain Hb levels among HD patients differed among groups with or without iron supplementation. Of 107 patients, 40 received intravenous iron supplementation due to iron deficiency (iron group) and 67 did not (non-iron group). In the iron group, the weekly therapy tended to require a lower total CERA dose compared with the biweekly therapy (274 ± 274 vs 381 ± 223 μg/12 weeks, P = 0.051). Changes in circulating hepcidin levels, a negative regulator of intestinal iron uptake, after 2 weeks of CERA treatment were significantly lower in the weekly therapy compared with the biweekly therapy (-4.2 ± 6.3 vs 11.1 ± 7.3 ng/mL, P = 0.015). In the non-iron group, there were no significant differences in total CERA dose or changes in hepcidin levels between the two therapies. Shortening the CERA treatment interval combined with iron supplementation may lead to the more efficient treatment of HD patients with iron deficiency.

Topics: Aged; Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Polyethylene Glycols; Renal Dialysis; Time Factors

Iron deficiency is a common etiology of anemia that causes suboptimal response to erythropoietin therapy in hemodialysis (HD) patients. This study investigated the association between vitamin D receptor (VDR) genetic variant (FokI) rs2228570 with iron indices (serum iron, transferrin, transferrin saturation, and ferritin). Sixty adequately hemodialyzed patients subdivided into two groups; 31 patients with transferrin saturation (TSAT) < 20% and 29 with TSAT > 20% who received I.V sodium ferric gluconate, calcium, and vitamin D. Sixty normal healthy were selected as the control group.. VDR genetic variant (SNP rs2228570) was genotyped in all subjects using PCR/RFLP. HD patients showed a higher frequency of rs2228570 FF genotype (38.3%) than controls (31.7%). The frequency of ff genotype and f allele in patients (8.4 and 35% respectively) were significantly lower than controls (25 and 46.7% respectively). Allele model (f vs. F): OR 0.721, 95% CI 0.521-0.998, P = 0.049. While (ff vs. FF): OR 0.452, 95% CI 0.223-0.917, P = 0.028. The distribution of Ff + ff genotypes in HD cases with TSAT > 20% was higher than in HD cases with TSAT < 20%, Dominant model (Ff +ff vs FF): OR 2.753, 95% CI 1.902-3.409, P = 0.048. f allele showed lower frequency in low TSAT group than high TSAT group (27.4 vs. 43.1%) with significant P value (P = 0.042) with allele model (f vs. F): OR 2.012, 95% CI 1.923-4.226, P = 0.042. Fok-1 ff, Ff + ff genotypes were significantly associated with TSAT > 20% with a protective effect against low TSAT in HD patients.

Topics: Adult; Anemia, Iron-Deficiency; Case-Control Studies; Erythropoietin; Female; Ferritins; Genetic Predisposition to Disease; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Polymorphism, Genetic; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Transferrin

Iron and erythropoietin deficiencies are determinants of anemia in chronic kidney disease. In hemodialysis (HD) patients, intravenous (IV) iron is associated with a greater hemoglobin (Hb) production and better erythropoietin response but may be associated to hypersensitivity reaction. After the 2013 European Medicines Agency report regarding early detection/management of iron allergic reactions, IV iron administration dramatically reduced in Italian Hemodialysis-Limited-Assistance-Centre (HD-CAL) where a physician is present only once a week. Objective of the study was providing an effective and secure IV iron administration protocol for HD-CAL patients. IV ferric carboxymaltose (FCM) administration was more effective and better tolerated than sodium ferric gluconate for iron deficiency correction and resolution of anemia in 24 patients undergoing HD in our HD-CAL. Six months of FCM IV treatment once a week increased ferritin and Hb compared to sodium ferric gluconate once a week leading to decreased erythropoietin consumption from 24 000 to 15 000 U/patient/week with an erythropoietin annual expense reduction. No blood transfusions, gastrointestinal intolerance or other adverse effects were reported. The FCM IV administration protocol for our HD-CAL patients was safe and no adverse events were reported, resulting in significantly increased ferritin, transferrin saturation, and Hb levels, reduction of erythropoietin requirements, and consequently reduction of erythropoietin expenses.

Topics: Administration, Intravenous; Ambulatory Care Facilities; Anemia, Iron-Deficiency; Clinical Protocols; Costs and Cost Analysis; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Humans; Iron; Italy; Male; Maltose; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

Iron deficiency anemia is common in general surgery patients during the perioperative period, which will increase the morbidity and mortality. Timely diagnosis and treatment of iron deficiency anemia in the perioperative period will improve the clinical outcome of patients and reduce the medical burden.Management of perioperative iron deficiency anemia includes familiar with the diagnosis and grading of anemia, monitoring patient's hemoglobin, treatment of anemic etiology, nutritional support, iron supplementation, implementation of restrictive transfusion strategy, application of erythropoietin, autotransfusion, etc.Multidisciplinary management of iron deficiency anemia is encouraged.. 普通外科患者在围手术期常见缺铁性贫血，缺铁性贫血会增加围手术期并发症发生率和病死率。围手术期及时诊断及治疗缺铁性贫血有助于改善患者临床转归，减轻医疗负担。围手术期缺铁性贫血管理的措施包括熟悉贫血的诊断及分级，监测患者血红蛋白，治疗贫血病因，营养支持，补充铁剂，实施限制性输血策略，应用促红细胞生成素，自体血回输等。本共识推荐通过多学科合作，诊断和治疗普通外科患者围手术期的缺铁性贫血。.

Topics: Anemia, Iron-Deficiency; Consensus; Erythropoietin; Hemoglobins; Humans; Iron; Surgical Procedures, Operative

In patients with pre-operative anaemia undergoing cardiac surgery, combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12 and oral folic acid reduces allogeneic blood product transfusions. It is unclear if certain types of anaemia particularly benefit from this treatment. We performed a post-hoc analysis of anaemic patients from a randomised trial on the 'Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery'. We used linear regression analyses to examine the efficacy of a combination anaemia treatment compared with placebo on the following deficiencies, each representing a part of the combination treatment: ferritin and transferrin saturation; endogenous erythropoietin; holotranscobalamine; and folic acid in erythrocytes. Efficacy was defined as change in reticulocyte count from baseline to the first, third and fifth postoperative days and represented erythropoietic activity in the immediate peri-operative recovery phase. In all 253 anaemic patients, iron deficiency was the most common cause of anaemia. Treatment significantly increased reticulocyte count in all regression analyses on postoperative days 1, 3 and 5 (all p < 0.001). Baseline ferritin and endogenous erythropoietin were negatively associated with change in reticulocyte count on postoperative day 5, with an unstandardised regression coefficient B of -0.08 (95%CI -0.14 to -0.02) and -0.14 (95%CI -0.23 to -0.06), respectively. Quadruple anaemia treatment was effective regardless of the cause of anaemia and its effect manifested early in the peri-operative recovery phase. The more pronounced a deficiency was, the stronger the subsequent boost to erythropoiesis may have been.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Blood Transfusion; Cardiac Surgical Procedures; Double-Blind Method; Drug Therapy, Combination; Erythropoietin; Female; Folic Acid; Hematinics; Humans; Iron; Male; Middle Aged; Postoperative Period; Preoperative Care; Reticulocyte Count; Vitamin B 12; Vitamin B Complex

To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs).. Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared.. The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P < .05).. In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Topics: Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Infant, Extremely Premature; Infant, Newborn; Iron-Dextran Complex; Male; Prevalence; Recombinant Proteins; Retrospective Studies

Severe traumatic injury leads to persistent injury-associated anemia that is associated with hypercatecholaminemia, systemic inflammation, increased hepcidin, and a functional iron deficiency. Vitamin D has been shown to reduce proinflammatory cytokines and hepcidin concentrations. This study aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia following blunt trauma.. A prospective observational cohort study comparing blunt trauma patients (n = 45) with elective hip replacement patients (n = 22) and healthy controls (n = 8) was performed. Bone marrow ferroportin, transferrin receptor, and erythroferrone expression was measured using quantitative polymerase chain reaction (qPCR). Plasma was assessed for systemic inflammation, erythropoietin (EPO), iron regulation, and vitamin D (25-OH) concentrations using enzyme-linked immunosorbent assay. Hemoglobin was measured on the day of discharge.. Compared with hip replacement, trauma patients had higher plasma interleukin-6 (90.1 vs. 3.8 pg/mL), C-reactive protein (6,223 vs. 2,612 ng/mL), and hepcidin (79.3 vs. 21.2 ng/mL) concentrations. Trauma patients had lower vitamin D (25-OH) (12.8 vs. 18.1 ng/mL) and iron (23.5 vs. 59.9 μg/mL) levels compared with hip replacement patients. Despite the higher hepcidin EPO levels, bone marrow erythroferrone expression was increased 69% following trauma.. Following elective hip replacement, patients did have anemia and impaired iron homeostasis without a significant change in inflammatory biomarkers, EPO, and vitamin D status. Vitamin D status did correlate with systemic inflammation, iron dysfunction, and persistent injury-associated anemia following severe blunt trauma. Further research is needed to determine whether supplementation with vitamin D in the trauma population could improve the persistent injury-associated anemia.. Prospective study, prognostic, level III.

Topics: Adult; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Erythropoietin; Female; Hemoglobins; Hepcidins; Humans; Iron; Male; Middle Aged; Prospective Studies; Vitamin D; Vitamin D Deficiency; Wounds, Nonpenetrating

Anemia and iron deficiency are highly prevalent in chronic kidney disease (CKD) and in chronic heart failure. Both may epidemiologically predict future renal and/or cardiovascular events. However, anemia treatment with either erythropoietin or erythropoiesis-stimulating agents failed to induce a prognostic benefit in either CKD or chronic heart failure. Instead, in the subgroup of chronic dialysis patients, liberal intravenous iron supplementation was beneficial, and ongoing clinical trials are testing the prognostic implication of intravenous iron supplementation in chronic heart failure. Finally, HIF stabilizers are a new treatment option for anemia in chronic kidney disease, and safety studies are currently ongoing in CKD patients. Whether patients suffering from chronic heart failure might also benefit from this treatment is currently unknown.. THERAPIE MIT EISENPRäPARATEN:  Mit PIVOTAL erschien 2018 die erste kardiovaskuläre Endpunktstudie zur Eisensubstitution bei Dialysepatienten, die eine prognostische Überlegenheit einer Hochdosiseisentherapie gegenüber einer restriktiveren Eisenapplikation aufzeigte. Mit AFFIRM-AHF, IRONMAN, FAIR-HF2 und HEART-FID überprüfen aktuell gleich 4 Studien die Bedeutung einer intravenösen Eisenapplikation auf kardiovaskuläre Endpunkte bei Patienten mit Herzinsuffizienz. AUSBLICK:  HIF-Stabilisatoren erlauben eine orale Anämie-Behandlung bei chronischer Nierenerkrankung. Erste klinische Studien zeigten eine „Nichtunterlegenheit“ von HIF-Stabilisatoren gegenüber der Behandlung mittels rekombinanten Erythropoetins (EPO)/Erythropoese-stimulierenden Agenzien (ESA) in Bezug auf den Hämoglobinanstieg. Finale Ergebnisse großer Studien mit kardiovaskulären Endpunkten sind aktuell noch ausstehend. In diesen Studien muss das Sicherheitsprofil von HIF-Stabilisatoren überprüft werden, da HIF-Stabilisatoren die Transkription zahlreicher Gene auch jenseits der Hämatopoese verändern. In der klinischen Kardiologie spielen HIF-Stabilisatoren aktuell (noch) keine Rolle. Unter der Therapie mittels SGLT-II-Inhibitoren konnte ein Anstieg des Hämatokrits beobachtet werden, welcher sich nicht allein durch diuretische Effekte erklären lässt. Die genaue pharmakodynamische Wirkweise ist noch offen.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Heart Failure; Hematinics; Humans; Iron; Renal Dialysis; Renal Insufficiency, Chronic

Topics: Anemia, Iron-Deficiency; Basic Helix-Loop-Helix Transcription Factors; Erythropoietin; Hepcidins; Humans; Iron; Oxygen

Optimizing preoperative anemia is a required component of the Joint Commission Patient Blood Management Certification and an important component of Enhanced Recovery After Surgery.. To describe a preoperative anemia protocol developed and implemented at the Kaiser Permanente San Jose Medical Center in California to facilitate preoperative identification and treatment of anemia.. The protocol included all operations at risk of causing substantial blood loss. It excluded emergent operations and those for which the patient had a normal last hemoglobin value within the prior 12 months unless newly developed anemia was suspected. Eligible patients were screened for laboratory evaluation, and those with anemia were treated for reversible causes. Consistency was ensured by physician, staff, and patient education, and by use of electronic health records. Administration of intravenous iron and erythropoietin and consultation with specialists were expedited as part of a management algorithm.. Among 510 patients enrolled during 1 year, 442 (87%) received anemia screening laboratory tests. Half of those with laboratory results were eligible for further optimization: 207 had anemia and 21 had iron deficiency without anemia. Among the 228 patients eligible for optimization, 189 (83%) had anemia addressed preoperatively. Of 129 patients with iron deficiency anemia, 102 (79%) received intravenous iron preoperatively, with a mean preoperative increase in hemoglobin level by 0.98 g/dL (n = 79).. Integration of specialty services, optimization of technology, and consistency across practitioners were crucial for successful implementation and sustainability of a preoperative anemia protocol developed to expedite and enhance best practices.

Topics: Anemia, Iron-Deficiency; Delivery of Health Care, Integrated; Erythropoietin; Feasibility Studies; Female; Humans; Iron; Male; Middle Aged; Preoperative Care; Trace Elements

Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross-sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti-cytokine-specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti-tumour necrosis factor-alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.

Topics: Adult; Anemia, Iron-Deficiency; Arthritis, Rheumatoid; Cross-Sectional Studies; Disease Progression; Erythropoietin; Female; Hemoglobins; Hepcidins; Humans; Inflammation; Joints; Male; Middle Aged

Anemia is very common among end stage patients with chronic renal failure (CRF). In this investigation, hematological parameters were examined in patients with end stage chronic renal failure from Khartoum, Sudan. A total of 70 patients and additional 30 healthy subjects were included in the study. All patients were under erythropoietin therapy whereas 42% were using iron supplements. The results showed that about 98% of CRF patients had anemia. Normocytic normochromic anemia was the most common type (94%) while few were suffering from microcytic hypochromic (6%) anemia. Low levels of hemoglobin, red blood cell count, hematocrits, serum iron, serum ferritin, and platelet counts were observed in the patient group compared to healthy controls (P<0.01). However, MCV, MCH and MCHC were not different between the two groups (P > 0.05). Moreover, no significant differences in all hematological parameters between patients with and without iron supplements were observed except for hemoglobin. In conclusion, anemia is common among end stage CRF in Sudan in spite of erythropoietin and iron therapy.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; Case-Control Studies; Dietary Supplements; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Sudan

A study of the clinical analysis of blood and major metabolites of ferrokinetics in 107 breast cancer patients before treatment was conducted. In 31 (28.9%) patients revealed anemic syndrome (AS). A feature of the AS is pronounced microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes. Most often (n = 22; 71%) there was iron deficiency (IDA), which was characterized by a low concentration of iron (F), ferritin (FR), hepcidin 25 (GP25), interleukin-6 (IL-6) and high - soluble transferrin receptors (rTFR), transferrin (TRF). In 9 (29%) patients with AS, on the basis of a high concentration of FR, GP25, IL-6, the anemia of chronic disease (AHZ) with functional iron deficiency (FDI) was established. In 23 (74.2%) patients with AS, the was a deficiency of erythropoietin (EPO), the lowest rates were found in the group of patients with a common tumor process and FDI, with less in patients with IDA.

Topics: Anemia; Anemia, Iron-Deficiency; Breast Neoplasms; Erythropoietin; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Interleukin-6; Iron; Iron Deficiencies; Receptors, Transferrin; Transferrin

Emerging data in chronic kidney disease (CKD) patients suggest that iron deficiency and higher circulating levels of erythropoietin (EPO) stimulate the expression and concomitant cleavage of the osteocyte-derived, phosphate-regulating hormone fibroblast growth factor 23 (FGF23), a risk factor for premature mortality. To date, clinical implications of iron deficiency and high EPO levels in the general population, and the potential downstream role of FGF23, are unclear. Therefore, we aimed to determine the associations between iron deficiency and higher EPO levels with mortality, and the potential mediating role of FGF23, in a cohort of community-dwelling subjects.. We analyzed 6,544 community-dwelling subjects (age 53 ± 12 years; 50% males) who participated in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study-a prospective population-based cohort study, of which we used the second survey (2001-2003)-and follow-up was performed for a median of 8 years. We measured circulating parameters of iron status, EPO levels, and plasma total FGF23 levels. Our primary outcome was all-cause mortality. In multivariable linear regression analyses, ferritin (ß = -0.43), transferrin saturation (TSAT) (ß = -0.17), hepcidin (ß = -0.36), soluble transferrin receptor (sTfR; ß = 0.33), and EPO (ß = 0.28) were associated with FGF23 level, independent of potential confounders. During median (interquartile range [IQR]) follow-up of 8.2 (7.7-8.8) years, 379 (6%) subjects died. In multivariable Cox regression analyses, lower levels of TSAT (hazard ratio [HR] per 1 standard deviation [SD], 0.84; 95% confidence interval [CI], 0.75-0.95; P = 0.004) and higher levels of sTfR (HR, 1.15; 95% CI 1.03-1.28; P = 0.01), EPO (HR, 1.17; 95% CI 1.05-1.29; P = 0.004), and FGF23 (HR, 1.20; 95% CI 1.10-1.32; P < 0.001) were each significantly associated with an increased risk of death, independent of potential confounders. Adjustment for FGF23 levels markedly attenuated the associations of TSAT (HR, 0.89; 95% CI 0.78-1.01; P = 0.06), sTfR (HR, 1.08; 95% CI 0.96-1.20; P = 0.19), and EPO (HR, 1.10; 95% CI 0.99-1.22; P = 0.08) with mortality. FGF23 remained associated with mortality (HR, 1.15; 95% CI 1.04-1.27; P = 0.008) after adjustment for TSAT, sTfR, and EPO levels. Mediation analysis indicated that FGF23 explained 31% of the association between TSAT and mortality; similarly, FGF23 explained 32% of the association between sTfR and mortality and 48% of the association between EPO and mortality (indirect effect P < 0.05 for all analyses). The main limitations of this study were the observational study design and the absence of data on intact FGF23 (iFGF23), precluding us from discerning whether the current results are attributable to an increase in iFGF23 or in C-terminal FGF23 fragments.. In this study, we found that functional iron deficiency and higher EPO levels were each associated with an increased risk of death in the general population. Our findings suggest that FGF23 could be involved in the association between functional iron deficiency and increased EPO levels and death. Investigation of strategies aimed at correcting iron deficiency and reducing FGF23 levels is warranted.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Biomarkers; Cohort Studies; Erythropoietin; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Male; Middle Aged; Mortality; Netherlands; Population Surveillance

Evaluation of anemic syndrome (AS) was performed in 79 patients with advanced stages of Hodgkin's lymphoma (LH) at various stages of chemotherapy (CT) according to the EACOPP-14 scheme. Against the background of the treatment, the number of erythrocytes and, accordingly, the HCT indices decreased with each subsequent cycle of chemotherapy (CTC) and reached the maximum reduction to 5, 6 th CCT. Absolute iron deficiency (IDA), which was combined with a low level of EPO and an inadequate degree of anemia, was found in a few LH patients (5 people, 6.3%). Functional iron deficiency (FDZH) was diagnosed in 9 patients (11.4%), had the same morphological signs as IDA. Namely, microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes (RET-HE). In contrast to IDA, patients with FDZh concentration of FR, GP-25 and IL-6 were high. Despite the fairly large reserves of iron, the level of rRTF testified to the "iron hunger" of the erythrocariocytes of the bone marrow, its index exceeded the upper limit of the norm, while RET-HE was low. In 34 (43%) patients, LH revealed a deficiency of endogenous erythropoietin (EPO), which was observed not only in patients with AHZ, but also in patients with IDA. Lower levels of EPO were detected in patients with leukopenia and very low erythropoietic activity of the bone marrow.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Hodgkin Disease; Humans; Reticulocytes

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus; Erythropoiesis; Erythropoietin; Female; Hematinics; Hepcidins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Renal Dialysis; Transferrin

Strategies to prevent anaemia in preterm infants include drawing fewer blood samples, the use of recombinant human erythropoietin and iron supplementation. Although iron sulfate is the most commonly used pharmaceutical formulation for iron supplementation, there are few studies comparing different iron salts in infants.. This is a study of retrospective data comparison of two groups of preterm infants receiving erythropoietin to evaluate the efficacy of iron bisglycinate chelate to iron sulfate.. Three-hundred infants of gestational age ≤32 weeks were enrolled: 225 were supplemented with iron sulfate (3 mg/kg/day) and 75 were supplemented with iron bisglycinate chelate (0.75 mg/kg/day). The effect on erythropoiesis was assessed with a general linear model that estimates the response variables (values for Haemoglobin, Haematocrit, absolute values and percentage Reticulocytes, Reticulocyte Haemoglobin content) based on treatment, time, birth weight, and gestational age.. Supplementation with iron bisglycinate chelate at a dose of 0.75 mg/kg/day demonstrated an efficacy comparable to iron sulfate at a dose of 3 mg/kg/day in both populations of preterm infants. The two cohorts had similar erythropoietic response, without significant differences.. The higher bioavailability of iron bisglycinate chelate resulted in a lower load of elemental iron, a quarter of the dose, and achieved equivalent efficacy compared to iron sulfate. Iron bisglycinate chelate may appear to be an alternative to iron sulfate in the prevention and treatment of preterm newborn anaemia.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Retrospective Studies; Treatment Outcome

Iron (Fe) status of neonates born to women carrying multiple fetuses might be compromised as a consequence of the high prevalence of maternal Fe deficiency and anemia coupled with an increased risk of preterm birth. This study aimed to characterize and identify determinants of anemia in this neonatal population.. Umbilical cord blood obtained from 183 neonates was utilized to assess hemoglobin (Hb), ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum Fe, erythropoietin, folate, vitamin B-12, C-reactive protein, and interleukin-6. Associations with maternal Fe status were explored.. Cord Hb or SF did not change significantly as a function of gestational age at birth (25-38 wks). Neonates born to women who were obese prior to pregnancy or smoked cigarettes during pregnancy had a 4-5-fold greater odds of anemia at birth. Cord sTfR was the strongest indicator of cord Hb (P < 0.0001), and it was significantly associated with maternal sTfR at mid-gestation (P = 0.01) and delivery (P = 0.002). Cord Fe indicators were significantly associated with cord hepcidin, but not maternal hepcidin.. Screening for Fe status in neonates born to women carrying multiple fetuses is warranted, especially for those born to smokers or to women who are obese at entry into pregnancy.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Cohort Studies; Erythropoietin; Female; Ferritins; Fetal Blood; Folic Acid; Hemoglobins; Hepcidins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Iron; Obesity; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Premature Birth; Receptors, Transferrin; Smoking; Tobacco Use Disorder; Vitamin B 12; Young Adult

To study the effects of iron metabolism abnormality on EPO-STAT5 signaling pathway in anemia patients.. According to diseases, the patients were divided into 3 groups: lower risk myelodysplastic syndrome (MDS) group (30 cases) including 14 cases of non-iron over load and 16 cases of iron over load, 12 cases of them were treated by iron chelation therapy; anemia of chronic disease (ACD) group (12 cases) and iron deficiency anemia (IDA) group (12 cases). In addition, the healthy control group was selected. The iron metaloslism index (SF, SI, TIBC), serum level of EPO, plasma level of P-STAT5 and STAT-5 mRNA expression in peripheral blood cells were detected and compared in different groups. Moreover, the effects of iron metabolism abnormality on the expression of EPO and STAT5 in anemia patients were analyzed.. compared with non-iron over load group, the EPO level in iron over load group significantly increased (P<0.05), the expression of STAT5 mRNA and P-STAT5 significantly decreased (P<0.05). After iron chelation therapy, the EPO level in serum significantly decreased (P<0.05), the expression of STAT5 mRNA and P-STAT5 was up-regulated significantly (P<0.05). Compared with healthy control group, the expression of EPO in ACD group was down-regulated significantly, while the expression of STAT5 mRNA was not different, but the P-STAT5 expression was down-regulated significantly (P<0.05). Compared with the healtly control group, the EPO expression in IDA group was enhanced significantly (P<0.05), the expression of STAT5 mRNA and P-STAT5 were also significantly enhanced (P<0.05).. The excessive iron load or chronic inflammation may inhibit the activation of EPO-STAT5 signaling pathway and aggravate the anemia.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Humans; Iron; Signal Transduction; STAT5 Transcription Factor

Iron deficiency anemia (IDA) is common in children. Limited data exist on the efficacy and safety of ferumoxytol in children.. To assess the efficacy of 10 mg/kg dose given over 15-60 minutes in correcting IDA and report any adverse drug reactions (ADRs).. We conducted a retrospective review of all patients who received ferumoxytol infusions for the management of IDA by the Pediatric Blood Management Program between October 2010 and March 2015.. A total of 110 infusions were given to 54 patients. Compared with baseline preinfusion hemoglobin (Hb; 9.2 ± 1.9 g/dL), a significant rise was seen at 1 week and 4 weeks postinfusion (11.5 ± 1.5 and 11.8 ± 1.7 g/dL, respectively, P < 0.001). Also, a significant rise in serum ferritin at 1 week and 4 weeks postinfusion was seen (51 ± 71 vs 192 ± 148 and 89 ± 135 ng/mL, P < 0.001 and <0.035, respectively). Patients who concomitantly received erythropoietin had a significantly larger Hb rise from baseline than those who did not at 4 weeks (2.7 ± 2.2 vs 1.6 ± 1.1 g/dL, P < 0.017). ADRs included pruritus (n = 1), urticaria (n = 1), and multisymptom episodes (n = 3) that included shortness of breath, chest tightness, back pain, and epigastric cramping that responded to therapy with IV diphenhydramine and methylprednisolone.. Ferumoxytol was effective in treating IDA in our small study. Slow infusion rate and close monitoring allowed early detection of the infrequent ADRs.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Erythropoietin; Female; Ferrosoferric Oxide; Hemoglobins; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Methylprednisolone; Pruritus; Retrospective Studies; Young Adult

Objective Iron deficiency anemia (IDA) has become important with regard to mortality in hemodialysis (HD) patients. Therefore, it is necessary to optimize the treatment of these patients. Methods IDA in end-stage renal disease patients on HD was observed in 42 (33.6%) of 125 patients. We examined the influence of daily orally iron [sodium ferrous citrate (SFC) iron/tablet 50 mg, 1-2 tablets] on the renal function markers, anemia and iron data for about 6 months. Results The hematocrit and hemoglobin levels were significantly increased in the patients treated with SFC [hematocrit: before 28.5%±2.1% (mean ± standard deviation), 1st month 30.0%±2.3%, p<0.05; 3rd month 32.4%±2.9%, p<0.05; 6th month 31.3%±3.4%, p<0.05; and hemoglobin: before 9.25±0.70, 1st month 9.72±0.71, p<0.05; 3rd month 10.54±0.96, p<0.05; 6th month 10.25±1.21 g/dL, p<0.05]. The transferrin saturation (TSAT) and serum ferritin levels were significantly increased in the patients treated with SFC (TSAT: before 21.5%±10.0%, 1st-3rd month, 34.1%±15.1%, p<0.05; 6-8th month 34.7%±11.9%, p<0.05; and ferritin: before 38.2±37.1, 6-8th month 67.5±44.0 ng/mL, p<0.05). The present findings clearly indicate that oral iron is an effective route of iron supplementation in HD patients, and no adverse effects associated with SFC occurred during the treatment and follow-up period. Conclusion Our results clearly indicate that oral iron delivered via SFC is a well-tolerated and effective form of iron supplementation in long-term HD and IDA patients in Japan.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Citric Acid; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hematocrit; Hemoglobins; Humans; Iron; Japan; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Erythropoietin; Hemoglobins; Humans; Iron

The role of inflammation in the development and progression of chronic kidney disease (CKD) in cats is not well characterized. Hepcidin is a recently discovered acute-phase protein (APP) that plays an important role in iron metabolism and contributes to the development of anemia in humans with CKD.. To compare serum APP concentrations, iron status, and erythropoietin (EPO) concentrations in healthy cats and cats with naturally occurring CKD.. A total of 18 healthy control cats and 38 cats with CKD.. Prospective study. After complete physical examination and routine blood analysis, the following tests were performed: serum amyloid A (SAA), haptoglobin (HAP), EPO, serum iron and ferritin concentration as well as total iron-binding capacity (TIBC). Serum hepcidin-25 concentration was measured by ELISA kit designed for use in humans.. Mean SAA and hepcidin concentrations were significantly higher and mean total iron and TIBC were significantly lower in the CKD group (P < .05). There was a significant positive correlation between serum creatinine concentration (CRT) and 2 of the APPs (SAA and hepcidin; P < .05). Increases in SAA and hepcidin were associated with decreases in TIBC and hematocrit in the CKD group. Fourteen (37%) of the cats with CKD were anemic, and these cats had significantly lower TIBC (P < .05), suggesting a functional iron deficiency. There was no association between survival time and APP, iron status, or EPO concentrations.. Our data suggest that CKD in cats is associated with systemic inflammation and altered iron metabolism. With further validation in cats, hepcidin assays may help better characterize these relationships.

Topics: Acute-Phase Proteins; Anemia, Iron-Deficiency; Animals; Case-Control Studies; Cat Diseases; Cats; Erythropoietin; Female; Ferritins; Hematocrit; Hepcidins; Iron; Male; Prospective Studies; Renal Insufficiency, Chronic; Serum Amyloid A Protein

The article presents data concerning clinical significance of interleukin 6, hepcidin-25 and its predecessor prohepcidin in differentiated diagnostic of anemic syndrome. The sampling of 192 workers of the oncologic center undergoing annual dispensarization was examined. The genuine reference values for immune enzyme (interleukin 6, hepcidin-25, prohepcidin, soluble receptors of transferrin, ferritin, erythropoietin) techniques are presented. The analysis of results demonstrated that values of interleukin 6, hepcidin-25, prohepcidin can be applied as additional diagnostic criteria of anemic syndrome and especially in differentiated diagnostic of anemia of chronic disease with functional iron deficiency. The carried out study is a new perspective direction of modern concept of iron metabolism in patients with anemic syndrome.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Ferritins; Hepcidins; Humans; Interleukin-6; Iron; Male; Middle Aged; Receptors, Transferrin

The UK-based National Institute for Health and Care Excellence (NICE) has updated its guidance on iron deficiency and anemia management in chronic kidney disease. This report outlines the recommendations regarding iron deficiency and their rationale. Serum ferritin alone or transferrin saturation alone are no longer recommended as diagnostic tests to assess iron deficiency. Red blood cell markers (percentage hypochromic red blood cells, reticulocyte hemoglobin content, or reticulocyte hemoglobin equivalent) are better than ferritin level alone at predicting responsiveness to intravenous iron. When red blood cell markers are not available, a combination of transferrin saturation < 20% and ferritin level < 100ng/mL is an alternative. In comparisons of the cost-effectiveness of different iron status testing and treatment strategies, using percentage hypochromic red blood cells > 6% was the most cost-effective strategy for both hemodialysis and nonhemodialysis patients. A trial of oral iron replacement is recommended in people not receiving an erythropoiesis-stimulating agent (ESA) and not on hemodialysis therapy. For children receiving ESAs, but not treated by hemodialysis, oral iron should be considered. In adults and children receiving ESAs and/or on hemodialysis therapy, intravenous iron should be offered. When giving intravenous iron, high-dose low-frequency administration is recommended. For all children and for adults receiving in-center hemodialysis, low-dose high-frequency administration may be more appropriate.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Iron; Meta-Analysis as Topic; Practice Guidelines as Topic; Renal Insufficiency, Chronic

Matriptase-2 (TMPRSS6) is an important negative regulator of hepcidin expression; however, the effects of iron overload or accelerated erythropoiesis on liver TMPRSS6 protein content in vivo are largely unknown. We determined TMPRSS6 protein content in plasma membrane-enriched fractions of liver homogenates by immunoblotting, using a commercial antibody raised against the catalytic domain of TMPRSS6. Plasma membrane-enriched fractions were obtained by centrifugation at 3000 g and washing. TMPRSS6 was detected in the 3000 g fraction as a 120 kDa full-length protein in both mice and rats. Feeding of iron-deficient diet as well as erythropoietin treatment increased TMPRSS6 protein content in rats and mice by a posttranscriptional mechanism; the increase in TMPRSS6 protein by erythropoietin was also observed in Bmp6-mutant mice. Administration of high doses of iron to mice (200, 350 and 700 mg/kg) decreased TMPRSS6 protein content. Hemojuvelin was detected in the plasma membrane-enriched fractions of control animals as a full length protein of approximately 52 kDa; in iron deficient animals, the full length protein was partially cleaved at the N-terminus, resulting in an additional weak band of approximately 47 kDa. In livers from hemojuvelin-mutant mice, TMPRSS6 protein content was strongly decreased, suggesting that intact hemojuvelin is necessary for stable TMPRSS6 expression in the membrane. Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo.

Topics: Anemia, Iron-Deficiency; Animals; Bone Morphogenetic Protein 6; Disease Models, Animal; Erythropoietin; Female; GPI-Linked Proteins; Hemochromatosis Protein; Iron; Iron Deficiencies; Iron Overload; Liver; Male; Membrane Proteins; Mice; Mice, Knockout; Mutation; Rats; Serine Endopeptidases; Sodium-Potassium-Exchanging ATPase

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Drug Substitution; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Trace Elements

Topics: Anemia, Iron-Deficiency; Erythropoietin; Hematinics; Humans; Iron; Iron Deficiencies; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

To test the correlation of the serum erythropoietin levels, serum transferrrin receptor levels and serum ferritin levels along with other hematological parameters in normal pregnant and anemic pregnant patients.. In a prospective study, 120 pregnant women were recruited between 18 and 36 weeks of gestation; 53 normal pregnant patients, 67 anemic pregnant patients, in which, 17 had mild, 30 had moderate anemia, 20 had severe anemia. A blood sample was taken. The various hematological parameters, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total iron binding capacity (TIBC), serum ferritin, percentage saturation of iron, serum erythropoietin (SEPO) levels, serum transferrin receptors (STfRS) were performed. For statistics, Student's 't' test, Pearson's Chi test, Mann Whitney test and Bartlett test were used as per data.. MCV was significantly reduced in anemic pregnancies as compared to non-anemic pregnancies (80.2±9.6 vs 94.12±9.8fl, p=0.001), MCHC was also reduced in them (30.2±3.38% vs 34.2±2.33%, p=0.176), TIBC was significantly increased in anemic pregnancies (343.31±28.54% vs 322.88±23.84%, p=0.001), serum ferritin was significantly reduced (24.9±10.48μg/L vs 31.03±9.98μg/L, p=0.001), percentage saturation of iron was also reduced (53.85±13.21% vs 62.04±15.79%, p=0.0024), serum erythropoietin levels were significantly higher in anemic women (26.24±26.61mU/ml vs 18.12±19.08mU/ml, p=0.064). The levels were significantly higher in severe anemia (46.5±46.8mU/ml than in moderate anemia 27.4±28.1mU/ml and mild anemia 22.8±22.8mU/ml. Serum transferrin receptors were significantly higher in anemic pregnancies than in non-anemic pregnancies (1.40±0.0802μg/ml vs 1.08±0.641μg/ml, p=0.019) with rise being higher in severe anemia (2.28±0.986μg/ml) than in moderate (1.4±0.816μg/ml) and mild anemia (1.16±0.702μg/ml).. Various hematological parameters especially sTfR, serum erythropoietin, serum ferritin and sTfR/log ferritin levels correlate with the severity of anemia.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Cross-Sectional Studies; Erythropoietin; Female; Ferritins; Humans; Pregnancy; Pregnancy Complications, Hematologic; Prospective Studies; Receptors, Transferrin; Young Adult

In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of "anemia of unknown etiology" and whether this trend persists after accounting for confounders.. This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index.. A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities.. We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology.

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Comorbidity; Erythropoietin; Female; Folic Acid Deficiency; Glomerular Filtration Rate; Hematologic Tests; Hemoglobins; Humans; Linear Models; Male; Middle Aged; Myelodysplastic Syndromes; Renal Insufficiency, Chronic; Retrospective Studies; Vitamin B 12 Deficiency

Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births.. We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia.. A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6.. The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 μg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery.. ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802.

Topics: Adult; Anemia, Iron-Deficiency; C-Reactive Protein; Erythropoietin; Female; Ferritins; Hemoglobins; Hepcidins; Humans; Inflammation; Interleukin-6; Iron; Iron Deficiencies; Longitudinal Studies; Nutritional Requirements; Nutritional Status; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Prevalence; Quadruplets; Triplets; Twins

To evaluate the effect of erythropoietin (EPO) treatment on retinal nerve fiber layer (RNFL) parameters in patients with chronic renal failure (CRF) undergoing peritoneal dialysis (PD).. Fifty-eight eyes of 29 patients with CRF undergoing PD were evaluated. Fifteen patients have been treated with EPO (group 1), 14 patients without EPO treatment (group 2), and 30 eyes of 15 age-matched normal control subjects were assessed in group 3. A complete ophthalmologic examination and RNFL measurements were performed for each patient after PD. Anemia parameters were also measured. RNFL thickness protocol was used to acquire circular scans of 3.4 mm in diameter around optic nerve. RNFL thicknesses were evaluated in 4 quadrants. Only the left eyes were recruited for statistical analysis. The mean and quadrantal RNFL thickness values in group 1 were compared with those of groups 2 and 3.. The mean RNFL thickness values in patients undergoing PD were statistically lower than the control group at superior, inferior, nasal, and temporal quadrant, respectively (P=0.03, 0.04, 0.04, and 0.03). Differences between the RNFL thickness values in group 1 and group 2 were statistically significant only in the temporal quadrant (P=0.02).. In patients with CRF undergoing PD, RNFL thickness parameters were found to be significantly reduced. The effect of EPO on RNFL parameters was statistically significant only in the temporal quadrant.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Intraocular Pressure; Kidney Failure, Chronic; Male; Middle Aged; Nerve Fibers; Peritoneal Dialysis; Recombinant Proteins; Retinal Ganglion Cells; Transferrin; Young Adult

Topics: Adult; Anemia, Iron-Deficiency; Case-Control Studies; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Middle Aged; Platelet Count; Thrombocytopenia

C.E.R.A. (continuous erythropoietin receptor activator, pegilated-rHuEPO ß) corrects and maintains stable hemoglobin levels in once-monthly administration in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the management of anemia with C.E.R.A. in CKD patients not on dialysis in the clinical setting.. Two hundred seventy two anemic CKD patients not on dialysis treated with C.E.R.A. were included in this retrospective, observational, multicentric study during 2010. Demographical characteristics, analytical parameters concerning anemia, treatment data and iron status were recorded.. C.E.R.A. achieved a good control of anemia in both naïve patients (mean Hemoglobin 11.6g/dL) and patients converted from a previous ESA (mean Hemoglobin 11.7g/dL). Most naïve patients received C.E.R.A. once monthly during the correction phase and required a low monthly dose (median dose 75 µg/month). The same median dose was required in patients converted from a previous ESA, and it was lower than recommended in the Summary of Product Characteristics (SPC). Iron status was adequate in 75% of anemic CKD patients, but only 50% of anemic patients with iron deficiency received iron supplementation.. C.E.R.A. corrects and maintains stable hemoglobin levels in anemic CKD patients not on dialysis, requiring conversion doses lower than those recommended by the SPC, and achieving target hemoglobin levels with once-monthly dosing frequency both in naïve and converted patients.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Diabetic Nephropathies; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Iron; Male; Middle Aged; Polyethylene Glycols; Renal Insufficiency, Chronic; Retrospective Studies; Young Adult

Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron-deficiency anaemia and iron overload, is common in many clinical conditions and impacts the health of up to 30% of the world's population. The proteins transmembrane protease, serine 6 (TMPRSS6; also termed matriptase-2), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis, by regulating expression of the iron regulatory hormone hepcidin. We have performed a systematic analysis of mice deficient in these three proteins and show that TMPRSS6 predominates over HFE and TFR2 in hepcidin regulation. The phenotype of mice lacking TMPRSS6 and TFR2 is characterized by severe anaemia and extramedullary haematopoiesis in the spleen. Stress erythropoiesis in these mice results in increased expression of the newly identified erythroid iron regulator erythroferrone, which does not appear to overcome the hepcidin overproduction mediated by loss of TMPRSS6. Extended analysis reveals that TFR2 plays an important role in erythroid cells, where it is involved in terminal erythroblast differentiation and the regulation of erythropoietin. In conclusion, we have identified an essential role for TFR2 in erythropoiesis that may provide new targets for the treatment of anaemia.

Topics: Anemia, Iron-Deficiency; Animals; Cell Differentiation; Erythroid Cells; Erythropoiesis; Erythropoietin; Hematopoiesis, Extramedullary; Hemochromatosis Protein; Hepcidins; Histocompatibility Antigens Class I; Kidney; Liver; Male; Membrane Proteins; Mice; Mice, Knockout; Receptors, Erythropoietin; Receptors, Transferrin; Serine Endopeptidases; Splenomegaly

Patients on hemodialysis (HD) are usually anemic because of defective erythropoeisis. Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient's response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 42 patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 ageand sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron and CRP were performed. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 ± 2.8 ng/mL and 8.5 ± 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 ± 2.4 ng/mL) while lower levels (16.9 ± 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as well as EPO resistance.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Case-Control Studies; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Hepcidins; Humans; Inflammation; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Transferrin; Young Adult

Anemia is a common comorbidity of patients with heart failure, and iron deficiency is known as one of the causes of anemia in heart failure. Recent studies have shown that iron deficiency alone, without overt anemia, is associated with poor outcomes in patients with heart failure. Thus, to minimize the mortality in patients with heart failure, it is important to understand the link between iron deficiency and cardiac function. Chronic untreated iron deficiency results in cardiac remodeling, and we have previously reported that erythropoietin (Epo) and cardiac Epo receptor (EpoR) signaling may be associated with its remodeling. However, the link between EpoR signaling and its remodeling remains to be elucidated. Herein, we investigated the role of EpoR signaling on cardiac remodeling in response to chronic iron deficiency.. Wild-type mice and transgene-rescued EpoR-null mutant mice, which express EpoR only in the hematopoietic lineage (EpoR-restricted mice), were fed with either a normal or an iron-restricted diet, and the molecular mechanisms were investigated.. Dietary iron restriction gradually induced anemia, Epo secretion, and cardiac hypertrophy in wild-type mice. In contrast, EpoR-restricted mice fed with an iron-restricted diet exhibited anemia, left ventricular dilatation, and cardiac dysfunction compared with wild-type mice. Interestingly, altered cardiac mitochondrial biogenesis was observed in EpoR-restricted mice following iron deficiency. Moreover, cardiac p53 expression was increased in EpoR-restricted mice compared with wild-type mice following iron deficiency.. These data indicate that EpoR signaling is associated with cardiac remodeling following chronic iron deficiency.

Topics: Anemia, Iron-Deficiency; Animals; Chronic Disease; Disease Models, Animal; Erythropoietin; Heart Failure; Iron Deficiencies; Male; Mice; Mice, Knockout; Myocardium; Receptors, Erythropoietin; Signal Transduction

This study aimed to analyze the iron deficiency index and erythrocyte parameters in anemic pregnant women and their newborns, and explore their implications for anemia during pregnancy. Pregnant women (70) in the third trimester with hemoglobin (Hb) <100 g/L who registered and delivered from June 2012-2013 were randomly selected as the observation group, 70 pregnant women at similar gestational ages with Hb >110 g/L were selected as the control group, and 70 newborns delivered by women in each group were included in corresponding offspring observation and control groups, respectively. Periodic physical examinations were conducted on the infants, and blood samples were drawn from the women and infants at birth, 42 days, 4 months, and 6 months old for detection of Hb and soluble transferrin receptor (sTfR) levels. Pregnant women and their 6-month-old infants in the observation group had significantly different Hb and sTfR levels compared to controls (P < 0.01). There were no significant differences in Hb and sTfR levels of infants at birth, 42 days, and 4 months old (P > 0.05). The detection rate of iron deficiency anemia (IDA) was significant, at 61.43% among 6-month-old infants in the observation group and 22.86% among controls (P < 0.01). There were no significant differences in the detection rate of IDA among infants at birth, 42 days, and 4 months old between observation and control groups (P > 0.05). Therefore, anemia during pregnancy is a major contributing factor of IDA and subclinical iron deficiency among 6-month-old infants.

Topics: Adult; Anemia, Iron-Deficiency; Erythrocytes; Erythropoietin; Female; Ferritins; Gestational Age; Hemoglobins; Humans; Infant; Infant, Newborn; Iron; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Transferrin; Young Adult

The study was carried out to analyze peripheral blood covering 23 patients with prevalent phases of Hodgkin lymphoma received no treatment previously. The clinical analysis of blood was implemented using hematologic analyzer Sysmex XE-2100. The content of ferritin, soluble receptors of transferrin and erythropoietin was estimated using enzyme-linked immunosorbent assay. The free hemoglobin was estimated using hemoglobin cyanide method. The direct Coombs test, counting of leukogram and analysis of morphology of erythrocytes were applied to all patients. The anemia is diagnosed in 19 patients (83%). In 18 out of them the anemic syndrome corresponded to anemia of chronic disease and in one patient asiderotic anemia was established. The rest of patients had no anemia. The anemia of chronic diseases characterized by microcytosis and hypochromia of erythrocytes, inadequate degree of anemia by production of erythropoietin and functional deficiency of iron in most of the patients. It should be emphasized that anemia of chronic diseases commonly is normocyte normochrome anemia whereas in patients with prevalent phases of Hodgkin Iymphoma the microcyte hypochrome anemia was detected before the treatment and it was followed by functional deficiency of iron. In patients without anemic syndrome microcytosis and hypochromia of erythrocytes were marked too. The techniques of laboratory diagnostic objectively reflecting iron metabolism (evaluation of level of soluble receptors of transferrin andferritin) and appropriate hormonal response to degree of anemia (production of erythropoietin) are to be included into algorithm of treatment of patients. The purpose is to timely detect type of anemia with the purpose of its appropriate correction prior to treatment onset.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Erythrocytes; Erythropoietin; Female; Ferritins; Hodgkin Disease; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Transferrin

Iron deficiency is more common in women due to uterine bleeding, which affects them throughout their fertile life. Additionally, iron needs increase physiologically during pregnancy and breastfeeding. Pregnant women therefore constitute one of the risk groups for iron deficiency. During the postpartum period, iron deficiency is the most common cause of anemia. Longer hospital stays and greater susceptibility to infections are potential consequences of postpartum anemia.

Topics: Anemia; Anemia, Iron-Deficiency; Blood Loss, Surgical; Blood Transfusion; Cesarean Section; Erythropoietin; Female; Gynecologic Surgical Procedures; Hematinics; Hemoglobins; Humans; Iron; Medical Errors; Menstruation; Multicenter Studies as Topic; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Preoperative Care; Prevalence; Prospective Studies; Puerperal Disorders; Randomized Controlled Trials as Topic; Recombinant Proteins

The appropriate use of intravenous (i.v.) iron is essential to minimise the requirements for erythropoiesis-stimulating agents (ESAs). The clinical efficacy of generic i.v. iron compared to the original formulation is controversial. We evaluated the changes that were induced after switching from a generic i.v. iron to an original formulation in a stable, prevalent haemodialysis (HD) population.. A total of 342 patients were included, and the follow-up period was 56 weeks for each formulation. Anaemia parameters and doses of ESA and i.v. iron were prospectively recorded before and after the switch from generic to original i.v. iron.. To maintain the same haemoglobin (Hb) levels after switching from the generic to the original formulation, the requirements for i.v. iron doses were reduced by 34.3% (from 52.8±33.9 to 34.7±31.8 mg/week, p<0.001), and the ESA doses were also decreased by 12.5% (from 30.6±23.6 to 27±21 μg/week, p<0.001). The erythropoietin resistance index declined from 8.4±7.7 to 7.4±6.7 IU/kg/week/g/dl after the switch from the generic to the original drug (p = 0.001). After the switch, the transferrin saturation ratio (TSAT) and serum ferritin levels rose by 6.8% (p<0.001) and 12.4% (p = 0.001), respectively. The mortality rate was similar for both periods.. The iron and ESA requirements are lower with the original i.v. iron compared to the generic drug. In addition, the uses of the original formulation results in higher ferritin and TSAT levels despite the lower dose of i.v. iron. Further studies are necessary to analyse the adverse effects of higher i.v. iron dosages.

Topics: Administration, Intravenous; Aged; Anemia, Iron-Deficiency; Chemistry, Pharmaceutical; Drugs, Generic; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Iron; Male; Prospective Studies; Renal Dialysis; Transferrin

Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations.. We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status.. The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum.. Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin.. In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Anemia, Iron-Deficiency; Biomarkers; Calcifediol; Cohort Studies; Cross-Sectional Studies; Erythropoietin; Female; Hemoglobins; Humans; Linear Models; Longitudinal Studies; Maternal Nutritional Physiological Phenomena; New York; Nutritional Status; Pregnancy; Pregnancy Complications; Prospective Studies; Risk; Vitamin D Deficiency

To investigate the expression level of erythropoietin (EPO) and ferritin before and after treatment of patients with iron deficiency anemia (IDA) so as to explore their clinical significance in diagnosis and discrimination.. The EPO and ferritin levels in serum of 37 patients with IDA were determined by using chemiluminescence analysis (CLIA method) and electrical chemiluminescence analysis (ECLIA method), 30 healthy people were randomly selected as normal controls.. (1) the sEPO level in IDA patients of group before treatment, group treated for 1 month and group treated for 2 months was higher than that in normal control group (P < 0.05). The level of sEPO of IDA patients in different groups after treatment was lower than that in IDA patients of groups before treatment, along with improvement of anemia status, the level of EPO was gradually reduced, and the level of sEPO in patients of group treated for 3 months was not statistical significant in comparison with that in normal control (P > 0.05). The level of ferritin in IDA patients before and after treatment was lower than that in normal control group (P < 0.05). The level of ferritin in IDA patient of groups after treatment was all higher than that in patients of groups before treatment, but comparision of serum ferritin level in patients of groups after treatment did not show statistical significance. (2) The level of logEPO in IDA patient before and after treatment was negatively related with level of Hb, but the level of ferritin in IDA patients was positively related with the level of Hb before treatment (r = 0.449, P = 0.005), the level of ferritin in patients of different group after treatment and in normal group did not related with level of HB. (3) The level of serum EPO in patients of severe anemia group was obviously higher than that in patients of moderate and mild anemia groups, and along with aggravation of anemia, the EPO level was gradually arised.. The serum EPO is involved in the process of erythrocyte hematopoiesis, and can indicate the level of anemia, its sensitivity for anemia is higher than that of ferritin, and has important clinical value for evaluating status of diseases, observing therapeutic efficacy and judging prognosisi of IDA.

Topics: Anemia, Iron-Deficiency; Case-Control Studies; Erythropoietin; Ferritins; Humans

Approximately 50 % of patients with inflammatory bowel disease (IBD) suffer from anaemia, with Fe deficiency being the most common cause. CD52 monoclonal antibody (mAb) targets the cell surface CD52 and is effective in depleting lymphocytes through cytolytic effects in vivo. The aim of the present study was to investigate the therapeutic effect of anti-mouse CD52 mAb on Fe-deficient anaemia in IBD. IL-10 knockout mice (IL-10- / -) of 12 weeks with established colitis were treated with anti-mouse CD52 mAb once per week for 2 weeks. Severity of colitis, blood T lymphocytes, blood Hb, haematocrit, plasma erythropoietin (EPO), serum Fe concentration, transferrin saturation, splenic Fe stores, expression of liver hepcidin mRNA, Western blotting of the phosphorylated form of Smad1/5/8 and total Smad1 were measured at the end of the experiment. IL-10- / - mice treated with CD52 mAb showed a reduction in the percentage of CD4+ and CD4+CD45+ T cells in blood and weight loss typically associated with colonic inflammation, serum levels of EPO, the expression of liver hepcidin mRNA and total Smad1 protein, while they showed an increase in Hb concentrations, haematocrit, levels of serum Fe, transferrin saturation and splenic Fe stores. The present results indicated that anti-CD52 therapy may ameliorate Fe-deficient anaemia by reducing colonic inflammation. These findings may open novel horizons in the treatment of patients with IBD by resetting of immunological homeostasis in the gut by depleting the activated T cells in the gut mucosa.

Topics: Anemia, Iron-Deficiency; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; CD4 Antigens; CD52 Antigen; Colitis; Erythropoietin; Glycoproteins; Hemoglobins; Hepcidins; Interleukin-10; Leukocyte Common Antigens; Liver; Lymphocyte Count; Mice; Mice, Inbred C3H; Mice, Knockout; RNA, Messenger; T-Lymphocytes; Weight Loss

A 16-year-old vasectomized male ring-tailed lemur (Lemur catta) with a history of suspected chronic renal failure was evaluated because of extreme lethargy, hyperpnea, and abscess of the right pectoral scent gland.. Examination of the anesthetized patient revealed an impacted right pectoral scent gland with serosanguineous exudate. A CBC and serum biochemical analysis revealed severe anemia, marked azotemia, hyperphosphatemia, and hypocalcemia.. Supportive care (including fluid therapy and phosphorus binder administration) was initiated for renal failure; the affected gland was cleaned, and antimicrobials were administered. The patient received 1 blood transfusion, and darbepoetin alfa was administered weekly to stimulate RBC production. Anemia and azotemia persisted. Three months after treatment started, serum iron analysis revealed that iron deficiency was the probable cause for the lack of a consistent regenerative response to darbepoetin injections. Iron dextran injections resulted in a marked regenerative response; however, serum biochemical analysis results after the second injection were consistent with hepatic injury. Hepatic enzyme activities normalized following discontinuation of iron dextran treatment, but the lemur's Hct declined rapidly despite supplementary iron administration PO. The patient developed severe mandibular osteomyelitis and was euthanized because of poor prognosis. Postmortem evaluation of hepatic iron concentration confirmed iron deficiency.. The family Lemuridae is considered prone to hemosiderosis and hemochromatosis, which delayed rapid diagnosis and treatment of the lemur's disease. Apparent hepatic injury following iron dextran injections further complicated treatment. Findings for this lemur support the use of species-specific total iron binding capacity and total serum iron and ferritin concentrations in evaluation of an animal with suspected iron deficiency.

Topics: Aging; Anemia, Iron-Deficiency; Animals; Blood Transfusion; Chemical and Drug Induced Liver Injury; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Hematinics; Iron; Iron-Dextran Complex; Lemur; Male; Renal Insufficiency, Chronic

Ever since the introduction of EPO, ESAs and iron dosing have been driven by financial incentives. When ESAs were a profit center for providers, large doses were used. With ESAs becoming a cost center, a new trend has appeared, gradually replacing their use with iron to achieve the same therapeutic effect at lower cost. This financially driven approach, treating ESAs and iron as alternatives, is not consistent with human physiology where these agents act in a complementary manner. It is likely that we are still giving unnecessarily large doses of ESAs and iron, relative to what our patients' true needs are. Although we have highlighted the economic drivers of this outcome, many other factors play a role. These include our lack of understanding of the complex interplay of the anemia of chronic disease, inflammation, poor nutrition, blood loss through dialysis, ESAs and iron deficiency. We propose that physiology-driven modeling may provide some insight into the interactions between erythropoiesis and ferrokinetics. This insight can then be used to derive new, physiologically compatible dosing guidelines for ESAs and iron.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Hematinics; Humans; Iron; Prospective Payment System; Renal Dialysis; Renal Insufficiency, Chronic

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.

Topics: Adolescent; Anemia, Iron-Deficiency; C-Reactive Protein; Cross-Sectional Studies; Delivery, Obstetric; Dietary Supplements; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Hepcidins; Humans; Inflammation; Interleukin-6; Iron, Dietary; Longitudinal Studies; Multivariate Analysis; Nutrition Assessment; Nutritional Status; Pregnancy; Prevalence; Receptors, Transferrin; Regression Analysis; Surveys and Questionnaires; Vitamin B 12

Iron homeostasis is a dynamic process that is tightly controlled to balance iron uptake, storage, and export. Reduction of dietary iron from the ferric to the ferrous form is required for uptake by solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both processes are proton dependent and have led to the suggestion of the importance of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated channel subfamily E, member 2 (KCNE2), in combination with potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1 results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on iron absorption has not, to our knowledge, been investigated. Here we report that Kcne2-deficient mice, in addition to the previously reported phenotypes, also present with iron-deficient anemia. Interestingly, impaired function of KCNQ1 results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients. We speculate that impaired function of KCNE2 could result in the same clinical phenotype.

Topics: Anemia, Iron-Deficiency; Animals; Diet, Western; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Genetic Heterogeneity; Hematocrit; Humans; KCNQ1 Potassium Channel; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Potassium Channels, Voltage-Gated; Sex Characteristics; Species Specificity; Specific Pathogen-Free Organisms; Transferrin

The clinical blood analysis implemented at modern hematological analyzers can be used as a foundation for primary differentiated diagnostic of anemic syndrome related to true and functional iron deficiency in oncologic patients. The normocyte normochromic anemia with normal and higher level of hemoglobin of reticulocytes (RET-HE) testifies presence in higher degree of anemia of chronic diseases which is more often combined with higher content of serum ferritin (Ferr), lower level of soluble receptors of ferritin (sTfR) and production of erythropoietin (EPO) inadequate to anemia degree. The microcyte hypochromic anemia can be present both under iron-deficient anemia and under functional iron deficiency as a result of its blocking in macrophages under anemia of chronic diseases in oncologic patients. Hence the differentiated diagnostic of these states demands additional analysis of content of serum ferritin, soluble receptors of ferritin and production of erythropoietin.

Topics: Anemia, Iron-Deficiency; Automation, Laboratory; Blood Chemical Analysis; Diagnosis, Differential; Erythropoietin; Ferritins; Iron-Binding Proteins; Neoplasms; Receptors, Cell Surface

The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Body Mass Index; C-Reactive Protein; Dietary Supplements; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Hepcidins; Humans; Iron, Dietary; Linear Models; Male; Middle Aged; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Biomarkers; Blood Specimen Collection; Clinical Laboratory Techniques; Erythropoietin; Hepcidins; Humans; Iron; Iron Deficiencies; Receptors, Transferrin

Topics: Adult; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Fluid Therapy; Glucaric Acid; Hematinics; Humans; Jehovah's Witnesses; Male; Oxygen Inhalation Therapy; Recombinant Proteins; Severity of Illness Index; Vitamin B 12; Vitamin B Complex

Current knowledge indicates that there is a close connection between being overweight, obesity and iron metabolism disorders,but the underlying mechanism is unclear. Hepcidin could be a major contributor to poor iron status observed in the obese population.. The study was performed in 58 obese elderly individuals (F/M 34/24) aged 65-91 (78.92 ± 8.32) years. The controlgroup consisted of 15 non-obese elderly volunteers, age- and sex-matched. Based on the WHO definition, 36 (62%) obese individualswere diagnosed with normo- or microcytic anaemia. The following parameters were determined: prohepcidin, haemoglobin, serum iron,erythropoietin, ferritin and C-reactive protein (CRP).. Prohepcidin concentrations were significantly increased in obese elderly individuals without anaemia compared to obese andanaemic (p < 0.01) as well as non-obese volunteers (p < 0.01). In obese individuals with anaemia there was a decrease in serum iron,concomitant with increased levels of erythropoietin and CRP compared to two other groups. Ferritin concentration was increased inobese people (with and without anaemia) compared to the non-obese group. Serum prohepcidin levels were positively correlated withfat mass percentage in obese individuals without and with anaemia (r = 0.32; p = 0.02).. Results of this preliminary study suggest that body fat content does have an impact on prohepcidin concentration, andthereby on iron homeostasis.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Erythropoietin; Female; Ferritins; Hepcidins; Humans; Male; Middle Aged; Obesity; Risk Factors; Serum Albumin

In July 2010 end stage renal disease anemia correction was incorporated to the program of explicit health guaranties of the Ministry of Health. The treatment plan included intravenous iron and erythropoietin. The prescription of these medications carne from the deriving health organizations.. To describe the results of that program in 11 dialysis facilities belonging to Fresenius Medical Care (a private organization) distributed in the six Metropolitan Health Services (MHS) in Santiago, Chile.. We selected 328 patients who remained in dialysis treatment at least between June 2010 and March 2011 and had a packed red cell volume lower than 30%, representing the target of the Plan. The evolution of packed red cell volume and the proportion of anemic patients in the facilities from each MHS were evaluated.. The two above mentioned variables began to improve only in December 2010. In no MHS, with the exception of the Eastern MHS, the mean hematocrit improved to higher than 30%, nor was the proportion of anemic patients reduced to lower than 50%.. Treatment of anemia of end stage renal disease in dialysis, implemented by the explicit health guaranties program of the Ministry of Health, was ineffective in almost all MHS in Santiago.

Topics: Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Hematocrit; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Program Evaluation; Renal Dialysis

Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation.. Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01).. In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients' iron stores than by inflammation.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Cross-Sectional Studies; Erythropoietin; Female; Heart Failure; Hemoglobins; Hepcidins; Humans; Iron; Male; Middle Aged; Odds Ratio; Outpatients; Receptors, Transferrin; Tumor Necrosis Factor-alpha

Mutations in transmembrane protease, serine 6 (TMPRSS6) cause iron refractory iron deficiency anemia (IRIDA). Parenteral iron administration may slightly improve hemoglobin level but is troublesome for patients. Optimal treatment has yet to be determined. We identified five patients from four independent families displaying the IRIDA picture with truncating biallelic mutations in TMPRSS6, one of which is novel. Liver iron determined by superconducting quantum interference device biosusceptometry ranged from 390 to 720 µg Fe/g wet weight (normal range 100-500; n = 3). Intestinal iron absorption (12 and 32 %, normal range 10-50; n = 2) and 59Fe erythrocyte incorporation after ingestion of 59Fe (57 and 38 %, normal range 70-90; n = 2) were inadequately low for iron-deficient anemic individuals. Baseline serum erythropoietin was elevated or borderline high in four patients. Administration of recombinant human erythropoietin (rhEPO) at up to 273 and 188 U/kg body weight/week alone did not improve anemia or result in a decrease of urinary hepcidin in two individuals. In conclusion, the ability of exogenous rhEPO to increase hemoglobin level appears to be impaired in IRIDA.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Erythropoietin; Female; Humans; Male; Membrane Proteins; Phenotype; Recombinant Proteins; Serine Endopeptidases; Young Adult

The diagnosis of iron deficiency anemia (IDA) in the context of the anemia of chronic disease (ACD) in elderly patients is often difficult due to the existence of many disorders. Recent studies have shown that hepcidin measurement (combined with the existing diagnostic methods) may possibly help in the differential diagnosis of IDA and ACD.. The aim of the study was to evaluate the differential diagnostic value of serum prohepcidin in elderly patients with IDA and ACD.. The study included 65 individuals aged 65 years or more: 26 patients with ACD, 13 patients with IDA, and 26 age-matched controls. Prohepcidin, ferritin, soluble transferrin receptor, erythropoietin, and interleukin 6 (IL-6) were measured using the commercially available enzyme-linked immunosorbent assay kits. Complete blood count, total iron-binding capacity (TIBC), and iron, transferrin, and C-reactive protein (CRP) levels were assayed using the standard laboratory methods.. Prohepcidin concentrations were similar in patients with ACD (196.59 ng/ml) compared with those with IDA (230.16 ng/ml) (P = 0.35). Patients with ACD had significantly lower levels of TIBC compared with those with IDA (P <0.0001). Serum ferritin concentration in patients with ACD was almost 20-fold higher compared with those observed in patients with IDA (P <0.0001). CRP and IL-6 concentrations in patients with ACD were significantly higher compared with those with IDA.. The results of the study indicate that serum prohepcidin has limited value in the differential diagnosis of IDA and ACD in elderly patients.

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Diagnosis, Differential; Erythropoietin; Female; Ferritins; Hepcidins; Humans; Interleukin-6; Iron; Male; Predictive Value of Tests; Receptors, Transferrin

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia.. Platelet counts were analyzed before and after iron therapy from four prospective clinical trials. Further, changes in hemoglobin, transferrin saturation, ferritin, C-reactive protein, and leukocyte counts, before and after iron therapy were compared. In a subgroup the effect of erythropoietin treatment was tested. The results were confirmed in a large independent cohort (FERGIcor).. A total of 308 patient records were available for the initial analysis. A dose-depended drop in platelet counts (mean 425 G/L to 320 G/L; p<0.001) was found regardless of the type of iron preparation (iron sulphate, iron sucrose, or ferric carboxymaltose). Concomitant erythropoietin therapy as well as parameters of inflammation (leukocyte counts, C-reactive protein) had no effect on the change in platelet counts. This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort (n=448, mean platelet counts before iron therapy: 383 G/L, after: 310 G/L, p<0.001).. Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia. Thus, iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD.

Topics: Anemia, Iron-Deficiency; Blood Platelets; C-Reactive Protein; Cohort Studies; Erythropoietin; Ferritins; Hemoglobins; Humans; Inflammatory Bowel Diseases; Iron; Iron Compounds; Iron Deficiencies; Leukocyte Count; Platelet Count; Prospective Studies; Thrombocytosis; Transferrin

A cohort of rhesus macaques used in neuroscience research was found at routine examinations to have chronic anemia (spun Hct less than 30%). Four anemic (Hct, 24.8% ± 3.4%) and 10 control (39.6% ± 2.9%) macaques were assessed to characterize the anemia and determine probable cause(s); some animals in both groups had cephalic implants. Diagnostic tests included CBC, bone marrow evaluations, iron panels, and serum erythropoietin and hepcidin concentrations. Serum iron and ferritin were 15.8 ± 11.1 μg/dL and 103.8 ± 53.1 ng/mL, respectively, for the anemic group compared with 109.8 ± 23.8 μL/dL and 88.5 ± 41.9 ng/mL, respectively, for the control group. Erythropoietin levels were 16.2 to over 100 mU/mL for the anemic macaques compared with 0 to 1.3 mU/mL for the control group. Hepcidin results were similar in both groups. Because the findings of low iron, high erythropoietin, and normal hepcidin in the anemic macaques supported iron-deficiency anemia or anemia of chronic disease combined with iron-deficiency anemia, a regimen of 4 doses of iron dextran was provided. In treated macaques, Hct rose to 36.3% ± 6.8%, serum iron levels increased to 94.0 ± 41.9 μg/dL, and erythropoietin levels fell to 0.15 to 0.55 mU/mL. Maintenance of normal Hct was variable between macaques and reflected individual ongoing clinical events.

Topics: Age Factors; Anemia, Iron-Deficiency; Animals; Animals, Laboratory; Antimicrobial Cationic Peptides; Biomarkers; Blood Cell Count; Bone Marrow Examination; Chronic Disease; Dietary Supplements; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Hepcidins; Iron; Iron Compounds; Macaca mulatta; Male; Monkey Diseases; Time Factors; Treatment Outcome

A novel polysaccharide named Angelica sinensis polysaccharide (ASP) was obtained from the powdered and defatted roots of A. sinensis (Oliv.) Diels. The molecular weight of ASP was determined to be 78 kDa and was 95.0% sugars consisting of mostly arabinose, glucose, and galactose with a molar ratio of 1:5.68:3.91. A previous study indicated that ASP may increase plasma iron levels by suppressing the expression of hepcidin, a negative regulator of body iron metabolism, in the liver. The present study aims to clarify the inhibitory effect of ASP on hepcidin expression in rat models of iron deficiency anemia (IDA), and clarify the mechanisms involved. It was demonstrated that ASP significantly reduced hepcidin expression by inhibiting the expression of mothers against decapentaplegic protein 4 (SMAD4) in liver and stimulating the secretion of erythropoietin, which further downregulated hepcidin by repressing CCAAT/enhancer-binding protein α (C/EBPα) and the phosphorylation of signal transducer and activator of transcription 3/5. The results indicate that ASP can suppress the expression of hepcidin in rats with IDA, and may be useful for the treatment of IDA.

Topics: Anemia, Iron-Deficiency; Angelica sinensis; Animals; Antimicrobial Cationic Peptides; Arabinose; CCAAT-Enhancer-Binding Protein-alpha; Down-Regulation; Erythropoietin; Hepcidins; Iron; Liver; Male; Phosphorylation; Plant Roots; Polysaccharides; Powders; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad4 Protein; STAT3 Transcription Factor; STAT5 Transcription Factor

The algorithm of analysis of blood of oncologic patients with anemic syndrome was elaborated using large clinical sampling (n = 284). It is established that 72% of oncologic patients developed anemia by kind of chronic diseases anemia. However in some patients the anemic syndrome was caused by the iron deficiency The cases of B12 deficient, autoimmune hemolytic anemia were registered and inefficient erythropoiesis under metastatic lesion of bone marrow and myelodysplasia syndromes as well. The high importance of methods of objective evaluation of iron resources (level of ferritin and soluble receptors of transferrin), erythropoietic activity of bone marrow (reticulocytes and reticulocyte indices) and adequate response to anemia degree (level of endogenic erythropoietin). The possibility to detect the concentration of hemoglobin in reticulocytes makes it possible to monitor the restoration of hemoglobin content on early stages of treatment of patient with iron deficiency anemia.

Topics: Aged; Algorithms; Anemia, Iron-Deficiency; Clinical Laboratory Techniques; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Receptors, Transferrin; Reticulocyte Count; Reticulocytes

Topics: Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Heart Failure; Humans; Injections, Intravenous; Iron; Male; Middle Aged; Treatment Outcome

Dietary iron is particularly critical during periods of rapid growth such as in neonatal development. Human and rodent studies have indicated that iron deficiency or excess during this critical stage of development can have significant long- and short-term consequences. Since the requirement for iron changes during development, the availability of adequate iron is critical for the differentiation and maturation of individual organs participating in iron homeostasis. We have examined in rats the effects of dietary iron supplement following neonatal iron deficiency on tissue iron status in relation to erythropoietic ability during 16 wk of postweaning development. This physiological model indicates that postweaning iron-adequate diet following neonatal iron deficiency adversely affects erythroid differentiation in the bone marrow and promotes splenic erythropoiesis leading to splenomegaly and erythrocytosis. This altered physiology of iron homeostasis during postweaning development is also reflected in the inability to maintain liver and spleen iron concentrations and the altered expression of iron regulatory proteins in the liver. These studies provide critical insights into the consequences of neonatal iron deficiency and the dietary iron-induced cellular signals affecting iron homeostasis during early development.

Topics: Age Factors; Anemia, Iron-Deficiency; Animals; Animals, Newborn; Bone Marrow; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Growth Differentiation Factor 15; Hematocrit; Hemoglobins; Homeostasis; Iron Deficiencies; Iron-Regulatory Proteins; Iron, Dietary; Liver; Male; Maternal Nutritional Physiological Phenomena; Polycythemia; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Spleen; Splenomegaly; Transferrin; Weaning

Topics: Anemia, Iron-Deficiency; Animals; Erythropoietin; Membrane Proteins; Mice; Mice, Knockout; Recombinant Proteins; Serine Endopeptidases

To assess changes in reticulocyte impedance volume, conductivity and light scatter (reticulocyte population data or RPD) obtained with the volume, conductivity and laser light scatter (VCS) technology in healthy subjects and in different erythropoietic states.. Blood samples were analysed with the Beckman-Coulter LH750 system, using the VCS method, from a group of 40 healthy subjects and three groups of patients with different types of untreated or treated anaemia: 24 cases of iron deficiency at the time of diagnosis, 16 patients with iron deficiency anaemia during intravenous iron administration, and 57 patients with chronic kidney disease undergoing dialysis and administration of rHu-erythropoietin and intravenous iron.. RPD data were reproducible. Average mean channels for volume were 50.9 for controls and 49.2, 55.7 and 64.0 for the three patient groups, respectively. Average mean channels for conductivity were 52.0 for controls and 59.8, 55.7 and 56.1 for the three patient groups. Average mean channels for light scatter were 108.4 for controls and 113.3, 117.3 and 128.2 for the three patient groups. SD data indicated increased dispersion in the patient groups.. When values in the patient groups are compared with reference values obtained in healthy controls, the main differences are found in impedance volume and light scatter, which were both increased in patients with stimulated erythropoiesis. These data indicate the opportunity to further evaluate the clinical usefulness of RPD in haematological diseases.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Blood Cell Count; Cell Size; Erythropoiesis; Erythropoietin; Female; Ferritins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Reticulocyte Count; Reticulocytes; Young Adult

Topics: Anemia, Iron-Deficiency; Animals; Erythropoietin; Membrane Proteins; Mice; Mice, Knockout; Recombinant Proteins; Serine Endopeptidases

Cadmium is a toxic heavy metal and distributed widely in the environment. In addition to damaging the liver, kidneys, and bone, cadmium causes anemia through hemolysis, iron deficiency, and insufficient erythropoietin (EPO) production (renal anemia) along with changes in iron metabolism. Here, we investigated the role of iron in the interdependent progress of three types of anemia in cadmium-injected rats fed iron-sufficient or iron-deficient diets for 1 or 3 months. Cadmium injections for 1 month induced renal anemia without renal injury. Injections for 3 months induced hemolysis, iron deficiency, and renal anemia, accompanied by hepatic and renal damage. Iron concentrations in the liver, kidney, and spleen were increased, derived from internally released iron from hemolyzed red blood cells, increased duodenal iron absorption, insufficient erythropoiesis, and hepatic ferritin overproduced by cadmium-induced interleukin-6. Therefore, the iron deficiency anemia was actually apparent. Cadmium suppressed renal EPO production through a direct effect, accumulated iron, and destruction of EPO-producing cells. Increased duodenal iron absorption could be attributed to hypertrophy of the duodenal mucosa derived from anemia. Thus, insufficient EPO production and iron accumulation are the central factors driving anemia in cadmium toxicity.

Topics: Anemia, Iron-Deficiency; Animals; Cadmium; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemolysis; Interleukin-6; Iron, Dietary; Kidney; Liver; Rats; Rats, Wistar; RNA, Messenger; Spleen

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Humans; Kidney Failure, Chronic; National Health Programs; Practice Guidelines as Topic; Societies, Medical; United Kingdom

To accurately determine the causes of anemia and proportion of unexplained anemia in a racially diverse cohort of older adults after a comprehensive and standardized evaluation.. We evaluated results from a single-institutional university anemia clinic. Patients with anemia, defined as a hemoglobin less than 13.0 g/dL for men and less than 12.0 g/dL for women, underwent a prospective standardized history, physical examination, and laboratory measures, with additional studies including bone marrow examination as indicated. Empiric treatment trials were given for identified deficiencies.. One hundred and seventy-four primarily community-dwelling adults aged 65 years and older were evaluable. African Americans accounted for 69% of patients and whites were 27%. Anemia etiologies included iron deficiency anemia at 25.3%, anemia of chronic inflammation at 9.8%, and hematologic malignancy in 7.5%. Unexplained anemia in the elderly accounted for 43.7% and predominated in both African Americans and whites. The prevalence of iron deficiency anemia and hematologic malignancies did not differ by race. Unexplained anemia in the elderly showed a consistent phenotype composed of a hypoproliferative mild-to-moderate anemia with suppressed serum erythropoietin. Specifically, erythropoietin levels showed no correlation with hemoglobin concentration in unexplained anemia in the elderly (r = -.15, p = .19) as opposed to iron deficiency anemia (r = -.63, p < .0001).. In summary, an intensive hematologic evaluation reveals a wide number of anemia etiologies among older adults, including 7.5% with hematologic malignancies; nevertheless, unexplained anemia in the elderly prevails as the most common category in whites and African Americans.

Topics: Aged; Aging; Anemia; Anemia, Iron-Deficiency; Black or African American; Chronic Disease; Cohort Studies; Erythropoietin; Female; Hematologic Neoplasms; Hemoglobins; Humans; Inflammation; Male; Outpatient Clinics, Hospital; Prevalence; Prospective Studies; Referral and Consultation; White People

Topics: Adult; Anemia, Iron-Deficiency; Antimalarials; Erythropoietin; Female; Hematocrit; Humans; Malaria, Falciparum; Male; Plasmodium falciparum

The study investigated the issues of iron metabolism under iron-deficiency anemia and chronic disorders anemia and dependencies of production of IL-1? and sICAM-1 immunoinflammatory markers from degree of severity and duration of anemia. The study data indicates that under iron-deficiency anemia lactoferrin and sICAM-1 are the negative regulators of hemopoiesis. The inhibition of transferrin expression by the proinflammatory cytokines is one of the causes of inefficient hemopoiesis under chronic disorders anemia.

Topics: Adult; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Erythropoiesis; Erythropoietin; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-1beta; Iron; Iron-Binding Proteins; Male; Middle Aged

The study sample included 170 patients with gynecological diseases, 5 patients with persistent anemia due to systematic blood disorder, 14 healthy patients. The decrease of hemoglobin level lower than 110 g/l is established in 25.7% gynecologic patients and most frequently in those with hysteromyoma. The study revealed that anemia developed due to the female reproductive system disorders and independently of clinically marked loss of blood is an. The biologic characteristic of anemia is the decrease of erythrocytes production under certain diseases against the background of inadequate production of endogenic erythropoietin. The effectiveness of treatment of iron-deficiency anemia is less under decrease of amount of erythrokaryocytes in bone marrow.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Bone Marrow; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Genital Diseases, Female; Hemoglobins; Humans; Leiomyoma; Middle Aged

To determine the efficacy and safety of subcutaneously administered recombinant human erythropoietin in combination with intravenous iron sucrose for the management of iron deficiency anaemia in gynaecological patients in Jinnah Postgraduate Medical Centre Karachi.. It was an interventional quasi experimental study carried out in the Department of Obstetrics /Gynaecology, at JPMC from 1st Nov 2007 to May 2008. All patients with indications for major Gynaecological surgery with iron deficiency anaemia having a mean haemoglobin level of 7 gm/dl were selected and the target haemoglobin was 11 gm/dl. Patients who were symptomatic, had chronic bleeding, renal failure or had signs of anaemia other than iron deficiency were excluded from the study. All investigations were done on day one before the start of therapy, and then treatment was initiated with recombinant human erythropoietin in a dose of 5000 IU subcutaneously and injection Iron Sucrose 200 mg in 100cc NaCI intravenously on 3 alternate days. The parameters checked in succession on day 4 and day 10 included increase in haemoglobin level, haematocrit, reticulocyte count, and time required to reach the target haemoglobin.. Twenty three patients fulfilled the inclusion criteria and were selected for the study. At the end of 10 days of starting therapy increase in haemoglobin was on an average of 2.8 gm/dl, increase in mean corpuscular volume was 4fl, Serum Iron increased by 99.86 ug%, total iron binding capacity decreased by 30.86%, transferrin saturation increased by 15.5% .There were no serious reactions to Erythropoietin or Iron sucrose. It is concluded that recombinant erythropoietin along with iron sucrose safely increased the haemoglobin level in 10 days to the target level thus rendering the patients fit for surgery and, none of the selected patients needed blood transfusion.

Topics: Academic Medical Centers; Adult; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gynecologic Surgical Procedures; Hematinics; Humans; Pakistan; Preoperative Care; Recombinant Proteins; Reticulocyte Count; Time Factors; Treatment Outcome

Iron deficiency is the main cause of failure to respond to erythropoietin (EPO) in haemodialysis patients. Several laboratory tests to detect the deficiency, ferritin and transferrin saturation (TSat) are the most commonly used but its limitations in this patient population are necessary to find other parameters to improve the identification of iron-deficient state.. To evaluate the ability of Reticulocyte Hemoglobin Equivalent (RET-He) to predict iron deficiency, taking as a reference standard to the increase of hemoglobin in response to iron intake.. 44 patients on chronic hemodialysis and fixed-dose EPO received 400 mg of intravenous iron. Were measured Hb, Ret-He, IRF, and ferritin prior to iron administration. After 20 to 30 days of completion of loading the patients were classified as responders if hemoglobin increased by at least 0.8 g / L and non-responders if this increase did not occur.. 25 patients were responders, the ROC curves analysis showed the Ret-He with the largest AUC of 0.862 similar to the AUC of 0.833 that showed the IST, but the first is more sensitive (72% CI 95%: 51-88% vs 52% 95% CI 31-72%) and similar specificity (94.7% CI 95%: 74-100% vs 100% 95% CI 82-100%). Ferritin AUC was 0.772 and finally the IRF AUC was 0.7. The Ret-He, to a cutoff of 29.5 pg was the best combination of sensitivity and specificity (72 and 94.7 respectively), and the sensitivity of the combination Ret-He/IST rose to 80% specificity 94.7%.. According to these results it could consider to Ret-He and the Ret-He/IST combination of clinical utility for the identification of the iron deficit in patients in chronic haemodialysis.

Topics: Anemia, Iron-Deficiency; Biomarkers; Cohort Studies; Erythropoietin; Female; Ferritins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Reproducibility of Results; Reticulocyte Count; ROC Curve; Sensitivity and Specificity

Anemia in IBD is the result of a combination of iron deficiency and anemia of chronic disease. Therapy of IBD is relief of inflammation, but the drugs usage may cause the development hemolytic anemia and myelodysplastic syndrome. We studied the effect of basic therapy on the incidence of anemia and assess the impact of modern biological therapies on the main markers of AHZ. A total of 153 patients with ulcerative colitis (UC) and 53 patients with Crohn's disease (CD), which at the time of the study received basic anti-inflammatory therapy for at least 1 year. All patients underwent blood tests, iron metabolism parameters were determined by the level of erythropoietin and G-gepsidina C reactive protein. Modern biological therapy increases the effectiveness of the treatment of anemia in patients with IBD. The use of Remicade gives a quick positive response, which is due to the decrease of gepsidin negative influence on iron metabolism and unlocking the synthesis of erythropoietin. The use of MSCs does not inhibit the synthesis of erythropoietin, and is likely to stimulate erythropoiesis at the erythroblast precursors.

Topics: Anemia, Hemolytic; Anemia, Iron-Deficiency; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antimicrobial Cationic Peptides; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Erythroblasts; Erythropoiesis; Erythropoietin; Hepcidins; Humans; In Vitro Techniques; Incidence; Infliximab; Male; Myelodysplastic Syndromes; Risk Factors; Time Factors

Renal anemia is caused by a lack of erythropoietin and iron, and is associated with increased morbidity and mortality in patients with chronic kidney disease. Iron deficiency is more common than previously thought. Diagnosis of absolute and relative iron deficiency is difficult because of the lack of an ideal diagnostic method. Adequate supplementation of iron in patients with renal anemia at a certain percentage of patients corrects anemia, while the other reduces the required doses of erythropoesis stimulating agents (ESAs), which can reduce treatment costs. In Department of Dialysis of General Hospital Bjelovar we carried out a retrospective study about treating renal anemia with iron during 36 months in 67 patients on chronic hemodialysis program in a period from 2007. to 2010. Our goal was to see if we adequately treat renal anemia with iron and to show the connection between the level of hemoglobin (Hb), ferritin and transferrin saturation (TSAT). The average value of ferritin in the 36 months follow-up was 196.8mcg/l, TSAT 24.16%, 107.8 g Hb/l. We conclude that the elevation of ferritin and TSAT correlates with the increase of Hb values in patients with renal anemia. Ferritin and TSAT values in our center are above the minimum criteria recommended by guidelines, but not within the target values for the treated population.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The percentage of hypochromic red cells (%Hypo) is a diagnostic tool that has been used with biochemical markers to diagnose iron disturbances and is incorporated to National Kidney Foundation KDOQI guidelines for monitoring recombinant human erythropoietin therapy. %Hypo measurement has been restricted to analysers manufactured by Siemens. Low haemoglobin density (LHD%), a new parameter provided by Beckman-Coulter, is derived from the traditional mean cell haemoglobin concentration (MCHC), using the mathematical sigmoid transformation [see equation in text]. This study aimed to establish LHD% values in the normal population and in different types of anaemia, to investigate its clinical usefulness in the study of iron status and its correlation with %Hypo. Samples from 449 patients [120 healthy individuals, 86 iron deficiency anaemia (IDA), 102 chronic kidney disease, 58 anaemia of chronic disease and 83 beta-thalassaemia carriers] were run sequentially on the LH 750 (Beckman-Coulter) and Advia 2120 (Siemens) analysers. The reliability of LHD% as a marker of iron deficiency was evaluated on a group of 152 consecutive patients with IDA. Good correlation was observed between %Hypo and LHD%, r(2) = 0.869. Receiver operating characteristic curve analysis for LHD% and the diagnosis of iron deficiency was: cut-off point 4.0%; area under the curve 0.976; sensitivity 95.2%; specificity 93.3%. There was a good level of agreement between LHD% and %Hypo. Both are suitable parameters for determining iron status and its availability for erythropoiesis, with the same clinical significance.

Topics: Anemia, Iron-Deficiency; Automation, Laboratory; beta-Thalassemia; Erythrocyte Indices; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Reference Values

Soluble Fas levels (sFas) are increased in the serum of uremic patients and are associated with the presence of anemia and recombinant human EPO (rHuEPO) dosage in dialysis patients. It is possible that sFas levels are associated with an increased need for serum erythropoietin levels (Epo) in chronic kidney disease and dialysis patients in order to maintain hematocrit (Hct) levels.. To investigate the relationship between serum sFas levels, serum Epo levels and the ratio between Epo levels and Hct in uremic patients.. We studied 52 predialysis chronic kidney disease patients (CKD; 33 M, 57 +/- 12 years, hematocrit (Hct) = 37 +/- 7%), 29 peritoneal dialysis patients (PD; 12 M, 54 +/- 14 years, Hct = 36 +/- 7%), 29 hemodialysis patients (HD; 19 M, 47 +/- 14 years, Hct = 33 +/- 5%) and 29 healthy volunteers (control group 17 M, 50 +/- 16 years, Hct = 43 +/- 3%). We examined the relationship between Hct and serum levels of Epo, sFas, C-reactive protein, IL-6 and iron status. The ratio of serum Epo divided by Hct (Epo/Hct) was used as an indicator of Epo responsiveness.. Compared to normal subjects, the CKD, PD and HD groups presented lower Hct levels and higher serum levels of sFas, Epo, Epo/Hct and IL-6. Serum levels of sFas correlated negatively with albumin (r = -0.24, p = 0.02), IL-6 (r = -0.18, p = 0.04) and Epo/Hct (r = -0.37, p < 0.001). In multivariate analysis, after adjusting for markers of iron store and inflammation, only sFas correlated with Epo/Hct. In the CKD group, there were negative correlations between serum levels of sFas and glomerular filtration rate (GFR) (r = -0.45, p < 0.001) and between Epo/Hct and GFR (r = -0.32; p = 0.02). There was a positive correlation between Epo/Hct and serum levels of sFas in the CKD group (r = 0.31, p = 0.03) and in the HD groups (r = 0.58, p = 0.001).. Our findings show that serum sFas is associated with higher Epo/Hct ratio, suggesting that sFas may be a marker of Epo hyporesponsiveness in uremia. Further studies are needed to determine whether sFas is just a marker of Epo hyporesponsiveness or is also involved in its pathophysiology.

Topics: Adult; Aged; Analysis of Variance; Anemia, Iron-Deficiency; C-Reactive Protein; Chi-Square Distribution; Erythropoietin; Fas Ligand Protein; Female; Humans; Inflammation; Interleukin-6; Iron; Kidney Failure, Chronic; Male; Middle Aged; Patient Selection; Regression Analysis; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Drug Evaluation, Preclinical; Erythropoietin; Gene Expression Regulation; Hepcidins; Membrane Proteins; Mice; Mice, Mutant Strains; Recombinant Proteins; Serine Endopeptidases

Topics: Administration, Oral; Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Humans; Injections, Intramuscular; Injections, Intravenous; Iron; Iron Overload; Maltose; Recombinant Proteins; Renal Dialysis

Accumulating data suggest potential clinical relevant relationships between hepcidin-25 levels, iron stores, erythropoiesis effectiveness, and epoetin dose. The immunometric methods and mass spectroscopy are currently used to measure hepcidin-25, but no standard exists, and values, although similar in trends, differ in absolute value.. To investigate hepcidin levels and their relationship with peripheral iron indices, inflammation, and anemia therapy in patients on hemodialysis (HD).. A cross-sectional study in 78 patients from a single HD center. Hepcidin-25 was measured with enzyme-linked immunosorbent assay (ELISA), using a commercial kit (Bachem, UK).. Hepcidin-25 levels were similar to those previously reported in studies using the same antibody (median 113 [95% CI; 107-122 ng/mL]) and significant but weak correlations of hepcidin with transferrin (R2=0.06; p<0.04) and ferritin (R2=0.09; p<0.01) were found. A model of multiple regression analysis explained 57% of variation along hepcidin quartiles. Lower hepcidin levels were associated with higher transferrin levels (odds ratio 1.05 [1.01-1.09]), bigger iron doses (odds ratio 1.09 [1.02-1.15]), and an increased darbepoetin resistance index (odds ratio 4.3E+15 [11.15-1.6E+30]). An elevated serum C reactive protein was associated with increased hepcidin levels (odds ratio 0.70 [0.49-0.99]), while a higher ultrafiltration volume (odds ratio 4.30 [1.28-14.51]) and the male sex (odds ratio 0.04 [0.00-0.80]) were related to lower hepcidin levels.. Cohort number and composition. Hepcidin-25 ELISA assay.. A low hepcidin level in hemodialysis patients with high epoetin resistance index could be a useful marker of iron-restricted erythropoiesis, but confirmation by a therapeutical trial is necessary.

Topics: Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; C-Reactive Protein; Cross-Sectional Studies; Darbepoetin alfa; Drug Resistance; Enzyme-Linked Immunosorbent Assay; Erythropoiesis; Erythropoietin; Female; Hepcidins; Humans; Inflammation; Iron; Iron Deficiencies; Iron Overload; Male; Middle Aged; Renal Dialysis; Transferrin

Topics: Adult; Age Factors; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Humans; Iron; Iron Deficiencies; Male; Menopause; Middle Aged; Risk Factors; Sex Factors

Iron deficiency anemia (IDA) affects many young women in sub-Saharan Africa. Its etiology is multifactorial, but the major cause is low dietary iron bioavailability exacerbated by parasitic infections such as malaria.. We investigated whether asymptomatic Plasmodium falciparum parasitemia in Beninese women would impair absorption of dietary iron or utilization of circulating iron.. Iron absorption and utilization from an iron-fortified sorghum-based meal were estimated by using oral and intravenous isotope labels in 23 afebrile women with a positive malaria smear (asexual P. falciparum parasitemia; > 500 parasites/μL blood). The women were studied while infected, treated, and then restudied 10 d after treatment. Iron status, hepcidin, and inflammation indexes were measured before and after treatment.. Treatment reduced low-grade inflammation, as reflected by decreases in serum ferritin, C-reactive protein, interleukin-6, interleukin-8, and interleukin-10 (P < 0.05); this was accompanied by a reduction in median serum hepcidin of ≈ 50%, from 2.7 to 1.4 nmol/L (P < 0.005). Treatment decreased serum erythropoietin and growth differentiation factor 15 (P < 0.05). Clearance of parasitemia increased geometric mean dietary iron absorption (from 10.2% to 17.6%; P = 0.008) but did not affect systemic iron utilization (85.0% compared with 83.1%; NS).. Dietary iron absorption is reduced by ≈ 40% in asymptomatic P. falciparum parasitemia, likely because of low-grade inflammation and its modulation of circulating hepcidin. Because asymptomatic parasitemia has a protracted course and is very common in malarial areas, this effect may contribute to IDA and blunt the efficacy of iron supplementation and fortification programs. This trial was registered at clinicaltrials.gov as NCT01108939.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Benin; Erythropoietin; Female; Ferritins; Food, Fortified; Growth Differentiation Factor 15; Hepcidins; Humans; Inflammation; Inflammation Mediators; Intestinal Absorption; Iron, Dietary; Isotope Labeling; Malaria, Falciparum; Parasitemia; Plasmodium falciparum; Sorghum; Young Adult

Secondary lack of iron in patients on hemodyalisis is the main cause of inadequate answer on therapy of recombinant human erythropoietin (rHuEPO). Therefore, it is very important to follow the status of iron in these patients.. The objectives of our study were to define the value of hemoglobin content in reticulocytes as predictor of functional iron deficiency on hemodialyzed treated patients with erythropoietin (rHuEPO) then evaluate the eficiency of using the value of hemoglobin content in reticulocytes in administration of iron HD (Patients on hemodialyzed ).. It is a prospective study which included 53 patients treated on chronical hemodialysis and continuing hospital peritoneal dialysis (CAPD), all patients were given additional iron therapy intravenously in order to keep the level of ferritin between 300 microg/l and 500 microg/ and transferrin saturation over 20%. The patients were both male and female randomly chosen. The following parameters conected to iron deficiency were compared in this study. The study was taken in the period from august to december 2008 at University Clinical Centar Tuzla.. The study included patients from chronical HD programme in therapy with rhEPO, iron intravenously, than patients on CAPD also in therapy with rh EPO and intravenously iron and patients on chronical HD with intravenously iron without rh EPO therapy. There wasn't any significant difference between numbers of male and female patients that were examined and in control group. In this study the following parameters conected to iron deficiency were compared. There wasn't any significant difference in values of seruum ferritin, Ret-he and hemoglobin between the examined and control group. Still, it's clear that members of the examined group had higher values of these parameters comparing to the control group. If we would use criterias like the saturation transferrin and the level of ferritin as referent standard we would have 26/53 (49.1%) patients with iron deficiency in the whole sample.. Following chematological and biochemic parameters in examined patients on HD are giving us essential information for planing and leading an adequate erythropoietin therapy. For the maximum effect of rhEPO therapy, an adequate compensation of iron is necessary.

Topics: Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Iron; Iron Deficiencies; Male; Recombinant Proteins; Renal Dialysis

In the early weeks of life, very low birth weight (VLBW) infants experience intense laboratory blood sampling leading to clinically significant anemia and the need for red blood cell transfusion. Although controversial, treatment with recombinant human erythropoietin (EPO) and iron has been recommended to stimulate erythropoiesis; optimal dosing of EPO and iron is still uncertain.. To assess the validity of a four-quadrant diagnostic plot of iron availability (ferritin index) versus iron demand for erythropoiesis (reticulocyte hemoglobin content, CHr) for differentiating iron status in anemic VLBW infants.. Study subjects were enrolled in a previously reported randomized controlled trial of clinically stable VLBW infants <31 weeks' gestation and <1,300 g at birth to receive 18 days of treatment with: group 1: oral iron; group 2: EPO + oral iron, and group 3: EPO + intravenous + oral iron.. At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group. By day 18, CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease. Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia, respectively.. The diagnostic plot for differentiating anemia in VLBW infants may be an informative, clinically useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states. Larger additional studies in difficult patient populations are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Body Weight; Drug Therapy, Combination; Erythropoietin; Ferric Compounds; Ferritins; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Iron; Nomograms; Randomized Controlled Trials as Topic; Recombinant Proteins; Reticulocytes

Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.

Topics: Adaptation, Physiological; Anemia, Iron-Deficiency; Animals; Blood Pressure; Body Weight; Disease Models, Animal; Erythropoietin; Heart; Heart Failure; Heart Rate; Hypertrophy, Left Ventricular; Hypoxia-Inducible Factor 1, alpha Subunit; Iron; Kidney; Male; Myocardial Contraction; Myocardium; Neovascularization, Physiologic; Phosphorylation; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; STAT3 Transcription Factor; Time Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

Topics: Adaptation, Physiological; Anemia, Iron-Deficiency; Animals; Erythropoietin; Heart Failure; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Myocardial Contraction; Myocardium; Neovascularization, Physiologic; Phosphorylation; Receptors, Erythropoietin; STAT3 Transcription Factor; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Hepcidin, a key regulator of iron metabolism, is a small antimicrobial peptide produced by the liver that regulates intestinal iron absorption and iron recycling by macrophages. Hepcidin is stimulated when iron stores increase and during inflammation and, conversely, is inhibited by hypoxia and augmented erythropoiesis. In many pathologic situations, such as in the anemia of chronic disease (ACD) and iron-loading anemias, several of these factors may be present concomitantly and may generate opposing signaling to regulate hepcidin expression. Here, we address the question of dominance among the regulators of hepcidin expression. We show that erythropoiesis drive, stimulated by erythropoietin but not hypoxia, down-regulates hepcidin in a dose-dependent manner, even in the presence of lipopolysaccharide (LPS) or dietary iron-loading, which may act additively. These effects are mediated through down-regulation of phosphorylation of Stat3 triggered by LPS and of Smad1/5/8 induced by iron. In conclusion, hepcidin expression levels in the presence of opposing signaling are determined by the strength of the individual stimuli rather than by an absolute hierarchy among signaling pathways. Our findings also suggest that erythropoietic drive can inhibit both inflammatory and iron-sensing pathways, at least in part, via the suppression of STAT3 and SMAD4 signaling in vivo.

Topics: Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Erythropoiesis; Erythropoietin; Female; Hepcidins; Hypoxia; Interleukin-6; Iron, Dietary; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Phosphorylation; Signal Transduction; Smad1 Protein; Smad4 Protein; Smad5 Protein; Smad8 Protein; STAT3 Transcription Factor

The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.. We considered data from 18,454 patients who were >or=65 yr, were in the US Renal Data System, started hemodialysis in 2003, and survived 3 mo on dialysis. We estimated the association between cumulative average epoetin dosage and survival through the subsequent 9 mo by using inverse probability weighting to adjust for time-dependent confounding by indication.. Survival was similar throughout the entire follow-up period for the three hypothetical treatment regimens selected: Low dosage 15,000 U/wk, medium dosage 30,000 U/wk, and high dosage 45,000 U/wk. Compared with a cumulative average dosage of 20,000 to 30,000 U/wk, the estimated hazard ratio (HR; 95% confidence interval [CI]) was 0.90 (0.52 to 1.54) for <10,000, 0.84 (0.67 to 1.05) for 10,000 to <20,000 U/wk, 0.96 (0.76 to 1.21) for 20,000 to <40,000 U/wk, and 0.91 (0.67 to 1.22) for >40,000 U/wk. In contrast, conventional unweighted models, which do not adequately adjust for time-dependent confounding by indication, indicated an association between high cumulative average epoetin dosage and increased mortality.. Our findings suggest that, on average, epoetin dosages >30,000 U/wk do not confer additional harm or benefit in elderly hemodialysis patients.

Topics: Age Factors; Aged; Anemia, Iron-Deficiency; Biomarkers; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Recombinant Proteins; Renal Dialysis; Risk Assessment; Time Factors; Treatment Outcome; United States

The mortality risk associated with attempting to raise hemoglobin (Hb) levels by increasing Epoetin alfa (EPO) doses in hemodialysis patients with persistently low Hb remains poorly understood. Design, setting, participants, & measurements. We included hemodialysis patients from a large dialysis provider between July 2000 and June 2001 who had EPO dose and Hb data for 6 consecutive months, and a mean Hb <11 g/dl in months 4 to 6 (sub-11 period). We identify predictors of EPO dose changes during the sub-11 period; evaluate the proportion of patients achieving a Hb >or=11 g/dl after the sub-11 period by dose-change categories; and evaluate the association between EPO dose changes and mortality risk.. Patients were more likely to receive greater EPO dose increases if they had lower EPO doses, higher Hb levels, or were recently hospitalized. Greater EPO dose increases elevated the likelihood of achieving an Hb >or=11 g/dl in the subsequent 3 mo. Larger EPO dose changes over the sub-11 period were not associated with an elevated mortality risk, but having an Hb <9 g/dl at the end of that period independent of dose change was associated with mortality risk. We found that patients receiving larger dose changes and whose resulting Hb level remained <9.5 g/dl at the end of the 3 mo were at elevated mortality risk.. In patients with persistently low Hb levels, mortality risk was strongly associated with the patient's ability to achieve a hematopoietic response rather than the magnitude of EPO dose titrations.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Biomarkers; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Animals; Cell Proliferation; Erythropoietin; Humans; Kidney Failure, Chronic; Megakaryocytes; Platelet Aggregation; Recombinant Proteins; Renal Dialysis; Thrombocytosis

The cardiorenal syndrome is a clinical and pathophysiological concept illustrating the relationship between the two organs, and is mainly based on the control of volemia. Heart failure is an example of this entity: when congestive heart failure becomes refractory, ultrafiltration by various modes of dialysis is needed. Ambulatory peritoneal ultrafiltration is a good alternative for the management of treatment-resistant congestive heart failure. Erythropoietin is the main treatment of anaemia of chronic renal failure for dialysed and predialysed patients, or patients with congestive heart failure and renal insufficiency. Correction of anaemia needs to be controlled at a maximal haemoglobin level of 12 g/dl.

Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Erythropoietin; Heart Failure; Hemoglobins; Humans; Kidney Failure, Chronic

The efficiency of therapy with the iron-containing preparation Ferro-Folgamma (Vervag Pharma, Germany) was evaluated in 62 men and women aged from 18 to 82 years with iron-deficiency anemia. Criteria for the efficiency were changes in clinical symptoms of anemia, hemoglobin level, erythrocyte and reticulocyte counts, packed cell volume, erythrocyte indices (mean erythrocyte volume, average content and concentration of hemoglobin in erythrocytes), erythropoietin level, and characteristics of iron metabolism (serum iron and ferritin levels, total iron-binding capacity of the serum, coefficient of ferritin saturation with iron), and drug tolerance. It was shown that Ferro-Folgamma is fairly well tolerated by the patients and produces good therapeutic effect when used to treat and prevent iron-deficiency anemia. Also, the study demonstrated that blood erythropoietin level being a sensitive indicator of hypoxia, it may be used as one of the most important criteria for the assessment of treatment efficiency in patients with iron-deficiency anemia.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferrous Compounds; Follow-Up Studies; Hemoglobins; Humans; Iron; Male; Middle Aged; Treatment Outcome; Young Adult

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFalpha and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFalpha, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Blood Chemical Analysis; Cohort Studies; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hepcidins; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Probability; Protein Precursors; Radioimmunoassay; Recombinant Proteins; Renal Dialysis; Statistics, Nonparametric; Treatment Outcome; Tumor Necrosis Factor-alpha

Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients.. The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level < or = 13 g/dL for men and < or = 12 g/dL for women.. The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 +/- 2.31 g/dL was significantly higher in male compared to female patients (13.26 +/- 2.31 g/dL vs 11.64 +/- 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations.. PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; Cadaver; Cyclosporine; Erythropoietin; Family; Female; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Male; Middle Aged; Prevalence; Tissue Donors

Topics: Adult; Aged; Alleles; Anemia, Iron-Deficiency; Case-Control Studies; Cation Transport Proteins; Drug Resistance; Erythropoietin; Female; Gene Frequency; Genetic Variation; Haplotypes; Humans; Kidney Failure, Chronic; Male; Middle Aged; Point Mutation; Polymorphism, Single Nucleotide; Recombinant Proteins; Renal Dialysis

Aims Chronic heart failure (CHF) is frequently associated with a decreased haemoglobin level, whereas the mechanism remains largely unknown. Methods and results One hundred consecutive CHF patients without anaemia or renal dysfunction based on non-cardiac reasons were enrolled. We explored determinants of anaemia (as iron parameters, erythropoietin, hepcidin and kidney function) including red cell volume (RCV) (by a 51 Cr assay) as well as related markers and plasma volume. The influence of each factor on haemoglobin concentrations was determined in a multiple regression model. Mean haemoglobin concentrations were 11.7 +/- 0.8 mg/dL in anaemic CHF patients and 14.4 +/- 1.2 mg/dL in non-anaemic patients. Corrected reticulocytes were lower in anaemic patients (35.1 +/- 15.7 vs. 50.3 +/- 19.2 G/L, P = 0.001), but the RCV was not reduced (1659.3 +/- 517.6 vs. 1826.4 +/- 641.3 mL, P = 0.194). We found that plasma volumes were significantly higher in anaemic CHF patients (70.0 +/- 2.4 vs. 65.0 +/- 4.0%, P < 0.001). Plasma volume was the best predictor of haemoglobin concentrations in the regression model applied (B = -0.651, P < 0.001, R(2) = 0.769). Conclusion Haemodilution appears to be the most potent factor for the development of low haemoglobin levels in patients with CHF. Our data support an additional independent, but minor influence of iron deficiency on haemoglobin concentrations in CHF patients.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Cross-Sectional Studies; Erythrocyte Volume; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Iron; Male; Middle Aged; Plasma Volume

High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels greater than 13 g/dL in patients with chronic kidney disease appear to be associated with increased mortality.. We conducted logistic regression and survival analyses in a retrospective cohort of long-term hemodialysis patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose-associated hemoglobin level of 13 g/dL or greater and mortality.. The national database of a large dialysis organization (DaVita) with 40,787 long-term hemodialysis patients during July to December 2001 and their survival up to July 2004 were examined.. Hemoglobin level, platelet count, and administered rHuEPO dose during each calendar quarter.. Case-mix-adjusted 3-year all-cause mortality and measures of iron stores, including serum ferritin and iron saturation ratio.. Higher platelet count was associated with lower iron stores and greater prescribed rHuEPO dose. Compared with a hemoglobin level of 12 to 13 g/dL, a hemoglobin level of 13 g/dL or greater was associated with increased mortality in the presence of relative thrombocytosis, ie, platelet count of 300,000/microL or greater (case-mix-adjusted death-rate ratio, 1.21; 95% confidence limits, 1.02 to 1.44; P = 0.03) as opposed to the absence of relative thrombocytosis (death-rate ratio, 1.04; 95% confidence limits, 0.98 to 1.08; P = 0.1). A prescribed rHuEPO dose greater than 20,000 U/wk was associated with a greater likelihood of iron depletion (iron saturation ratio < 20%) and relative thrombocytosis (case-mix-adjusted odds ratio, 2.53; 95% confidence limits, 2.37 to 2.69; and 1.36; 95% confidence limits, 1.30 to 1.42, respectively; P < 0.001) and increased mortality during 3 years (death-rate ratio, 1.59; 95% confidence limits, 1.54 to 1.65; P < 0.001).. Our results may incorporate uncontrolled confounding. Achieved hemoglobin level may have different mortality predictability than targeted hemoglobin level.. Iron depletion and associated relative thrombocytosis might contribute to increased mortality when administering high rHuEPO doses to achieve hemoglobin levels of 13 g/dL or greater in long-term hemodialysis patients. Randomized trials are needed to test these observational associations.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Chronic Disease; Cohort Studies; Dose-Response Relationship, Drug; Erythropoietin; Female; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney Diseases; Logistic Models; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Survival Analysis; Thrombocytosis

Anaemia is prevalent in chronic kidney disease (CKD) and induces significant changes in heart and kidney. In this study, we evaluated the relationship between iron metabolism, hepcidin and inflammation focusing on left ventricular (LV) function, in a remnant kidney rat model.. Rats with 5/6 subtotal nephrectomy (STNx) and sham operation. Haemoglobin (Hb), serum iron (SI), fractional shortening (FS%) by echocardiograms were evaluated. Six months after STNx, the heart and kidney were processed by immunohistochemistry with antibodies against hypoxia-inducible factors (HIF)-1alpha, erythropoietin (EPO), pro-hepcidin, caspase-3, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6.. Hb (g/dL) STNx: 10.8 +/- 0.8, sham: 14.7 +/- 0.6 (P < 0.01); SI (microg/dL) STNx: 154.5 +/- 24.5, sham: 287.5 +/- 32.1 (P < 0.01); heart weight (g) STNx: 2.21 +/- 0.15, sham: 1.12 +/- 0.12 (P < 0.01); FS% STNx: 28.4 +/- 2.5, sham: 45.1 +/- 4.1 (P < 0.01). There was a correlation between Hb and FS% (r = 0.95; P < 0.01) and between SI and FS% (r = 0.86; P < 0.01) in the STNx group. Tissue ferritin was reduced in heart and in kidney in the STNx group (P < 0.01). HIF-1alpha was expressed in cardiomyocytes (positive cells/area) STNx: 32 +/- 5, sham: 4 +/- 1; and tubular cells in STNx group: 70 +/- 16, sham: 10 +/- 3, P < 0.01. Hepcidin (% staining/area) in heart STNx: 6.6 +/- 0.8, sham: 0.8 +/- 0.1; in kidney STNx: 9.7 +/- 2.6, sham: 3.7 +/- 0.9, P < 0.01. EPO (% staining/area) in heart STNx: 2.6 +/- 0.4, sham: 0.8 +/- 0.2; in kidney STNx: 10.2 +/- 1.4, sham: 1.2 +/- 0.6; P < 0.01. In STNx group positive caspase-3, TNF-alpha and IL-6 were detected in heart and renal cells.. Low LV performance is associated with iron deficiency anaemia in rats with CKD. Furthermore, overproduction of HIF-1alpha and the activation of caspase-3 seem to be associated with iron deficiency and with inflammatory markers. Hepcidin seems to plays a key role in this mechanism.

Topics: Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Caspase 3; Erythropoietin; Ferritins; Hepcidins; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Interleukin-6; Kidney; Male; Myocardium; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Tumor Necrosis Factor-alpha; Ventricular Function, Left

Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.

Topics: Adolescent; Adult; Anemia; Anemia, Iron-Deficiency; Antimicrobial Cationic Peptides; Bangladesh; Biomarkers; Cross-Sectional Studies; Erythropoietin; Female; Hemoglobins; Hepcidins; Humans; Inflammation; Iron; Linear Models; Nutritional Status; Pregnancy; Pregnancy Complications; Young Adult

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: 15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 microg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Erythropoietin; Female; Humans; Incidence; Iron; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Prevalence; Prospective Studies; Regression Analysis; Spain

Anaemia is a common and serious complication in patients with end-stage renal disease. Iron therapy is crucial in managing anaemia and maintenance of haemodialysis (HD) patients. This study investigated the efficacy of both oral and intravenous (i.v.) therapies, and the possible factors deleteriously affecting patient response to iron therapy. Forty patients on maintenance HD from a single institution were enrolled in this 6-month retrospective study. Group I (n = 20) received i.v. two ampoules of atofen (ferric chloride hexahydrate 193.6 mg) per week for a total of 6 weeks (total dosage, 960 mg). Group II (n = 20) received oral ferrous sulphate S.C. Tab (ferrous sulphate 324 mg) one pill three times daily (total dosage, 63,000 mg). Patients whose haematocrit (Hct) level increased at minimum 3% within the period were classified as responders. Iron i.v. ferric chloride (960 mg) was more effective than oral ferrous sulphate (63,000 mg) in correcting anaemia in HD patients with iron deficiency. In group I, serum triglyceride (TG) levels were significantly lower in patients responding to i.v. iron therapy than in patients with no response. In group II, serum high-sensitive C-reactive protein (hs-CRP) level was significantly lower in patients responding to oral iron therapy than patients with no response. The i.v. ferric chloride is more effective than oral ferrous sulphate in treating anaemia in HD patients with iron deficiency. Serum hs-CRP and TG levels may be parameters for predicting hyporesponsiveness to oral and i.v. iron therapies, respectively.

Topics: Administration, Oral; Anemia, Iron-Deficiency; C-Reactive Protein; Chlorides; Erythropoietin; Female; Ferric Compounds; Ferritins; Ferrous Compounds; Hematinics; Hematocrit; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome

Under normal conditions, reticulocytes are the youngest erythrocytes released from the bone marrow into circulating blood. They mature for 1-3 days within the bone marrow and circulate for 1-2 days before becoming mature erythrocytes. Measurement of cellular hemoglobin concentration has long been reported by automated hematology analyzers as one of the red blood cell indices. The reticulocyte hemoglobin content (CHr or Ret-He) provides an indirect measure of the functional iron available for new red blood cell production over the previous 3-4 days. Measurement of reticulocyte hemoglobin content in peripheral blood samples is useful for diagnosis of iron deficiency in adults (Mast et al., Blood 2002;99:1489-1491) and children (Brugnara et al., JAMA 1999;281:2225-2230; Ullrich et al., JAMA 2005;294:924-930; Bakr and Sarette, Eur J Pediatr 2006;165:442-445). It provides an early measure of the response to iron therapy increasing within 2-4 days of the initiation of intravenous iron therapy (Brugnara et al., Blood 1994;83:3100-3101). Sequential measurements of reticulocyte hemoglobin content in patients with iron deficiency anemia provide a rapid means for assessing the erythropoietic response to iron replacement therapy (Brugnara et al., Blood 1994;83:3100-3101). It is also an early indicator or iron-restricted erythropoiesis in patients receiving erythropoietin therapy (Fishbane et al., Kidney Int 1997;52:217-222; Fishbane et al., Kidney Int 2001;60:2406-2411; Mittman et al., Am J Kidney Dis 1997;30:912-922; Tsuchiya et al., Clin Nephrol 2003;59:115-123; Chuang et al., Nephrol Dial Transplant 2003;18:370-377). Thus, reticulocyte hemoglobin content is a recent addition to an expanding list of biomarkers that can be used to differentiate iron deficiency from other causes of anemia.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; Biomarkers; Diagnosis, Differential; Erythropoiesis; Erythropoietin; Hemoglobinometry; Humans; Iron; Nephelometry and Turbidimetry; Reticulocytes; Sensitivity and Specificity

Intravenous iron supplementation is a recognized therapy for anemia in chronic hemodialysis patients, especially in those treated with erythropoietin. The vast majority of patients with chronic kidney disease (CKD) seem to be iron-deficient, as evaluated by the usual parameters and by iron staining on bone marrow biopsy, because of multiple forms of interference with all phases of iron metabolism. The need for iron supplementation in CKD patients becomes obvious. Intravenous iron was demonstrated to be superior to oral iron in hemodialysis patients. There is also evidence for the superiority of intravenous iron in peritoneal dialysis and in nondialysis-dependent CKD patients. On the other hand, intravenous iron could promote cytotoxicity and tissue injury, and exacerbate oxidative stress and thus endothelial dysfunction, as well as inflammation and the progression of both CKD and cardiovascular disease. Nevertheless, correction of anemia is effective in reducing oxidative stress and, consequently, cardiovascular risk. The overall risk-benefit ratio favors the use of intravenous iron alone or with an erythropoietic stimulating agent in the management of renal anemia. Clinical judgment is necessary in each individual case to diagnose iron deficiency and effectively use intravenous iron.

Topics: Anemia, Iron-Deficiency; Disease Progression; Erythropoietin; Humans; Inflammation; Injections, Intravenous; Iron; Kidney Failure, Chronic; Oxidative Stress; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Risk Assessment; Uremia

Recombinant human erythropoietin (rHuEpo) is a definitive treatment for anaemia in chronic kidney disease (CKD). During long-term rHuEpo treatment most patients develop and show persistent iron deficiency in spite of oral iron supplementation. Abnormalities of iron absorption and transport in the duodenum may contribute to this deficiency.. To investigate changes in iron absorption and transport in CKD and iron deficiency against the background of rHuEpo treatment, we used severely anaemic rats with adenine-induced renal failure (adenine rats) and sham-treated control rats given only the vehicle. After 4 weeks on adenine or the vehicle, the rats were divided into four groups according to whether or not they received rHuEpo for the next 4 weeks: rHuEpo(-)-adenine, rHuEpo(-)-control, rHuEpo(+)-adenine and rHuEpo(+)-control. We evaluated the effects of rHuEpo treatment on iron balance, duodenal mRNA expression of molecules related to iron absorption and transport and hepatic mRNA expression of hepcidin.. Treatment with rHuEpo improved anaemia and induced iron deficiency only in the adenine rats, in whom the expression of mRNAs for ferroportin 1 and hephaestin 1 increased and for divalent metal transporter 1 (DMT1) was unchanged. In contrast, control rats treated with rHuEpo showed no changes. Hepcidin mRNA expression was greater in adenine rats than in control rats.. In the adenine rats, rHuEpo treatment improved renal anaemia and induced persistent iron deficiency. An alteration of mRNA expression of molecules related to iron metabolism in renal insufficiency may be one of the reasons for this iron deficiency.

Topics: Adenine; Analysis of Variance; Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Disease Models, Animal; Erythrocytes; Erythropoietin; Hepcidins; Humans; Iron; Kidney Failure, Chronic; Kidney Function Tests; Male; Polymerase Chain Reaction; Probability; Random Allocation; Rats; Rats, Wistar; Recombinant Proteins; Renal Insufficiency; RNA, Messenger

Because serum ferritin and transferrin saturation (TS) have a limitation in estimating iron status in haemodialysis patients, the reticulocyte haemoglobin content (CHr) has been proposed as a new tool. We investigate the accuracy of CHr in comparison with conventional tests and the relationship between changes in CHr and haemoglobin levels after therapy. We selected 140 haemodialysis patients receiving rHuEPO and intravenous iron supplementation and measured their complete blood count, CHr and iron parameters. Iron deficiency was defined as a ferritin <100 microg/l and/or a TS <20%. Hb, CHr, ferritin and TS levels were determined 1 month after therapy. Fifty-three patients were iron deficient. CHr were distributed with 33.7 +/- 1.4 pg in the iron sufficient group and with 29.9 +/- 1.9 pg in the iron deficient group (P = 0.001). The cutoff value of CHr for detecting iron deficiency was <32.4 pg. In iron deficient patients, a significant correlation was found between CHr and TS. The change in CHr after therapy was significantly larger in iron-deficient patients, and a lower baseline CHr is associated with a greater haemoglobin change. CHr is useful in screening iron status in dialysis patients, and a CHr cut-off value of 32 pg is appropriate for the assessment of iron deficiency. Moreover, CHr may serve as a predictor of the response to anaemia treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reticulocytes; Transferrin

Topics: Anemia, Iron-Deficiency; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Ferric Compounds; Heart Failure; Hematinics; Homeostasis; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

We examined the adequacy of endogenous erythropoietin (EPO) levels for the degree of anaemia in patients with chronic heart failure (CHF) and its relation to prognosis.. We studied 74 anaemic CHF patients from a cohort of 240 patients. The adequacy of endogenous EPO levels was assessed by derived observed/predicted (O/P) ratio. A ratio value < 0.92 indicates EPO levels lower than expected, whereas a value > 1.09 indicates EPO levels higher than expected. The primary endpoint was mortality. During a median follow up of 4.9 years, 35 of the 74 (47.3%) anaemic patients died. EPO levels lower than expected were observed in 29 patients (39%), whereas EPO levels higher than expected were present in 22 anaemic patients (29%). The Kaplan-Meier analysis revealed that anaemic patients with EPO levels higher than expected had a significantly higher mortality rate compared to patients with EPO levels as expected or EPO levels lower than expected (log-rank: P = 0.024). A higher O/P ratio was an independent predictor of increased mortality risk adjusted for variables including age, sex, haemoglobin, NT-proBNP, and renal function; hazard ratio (HR): 1.020 95%CI (1.004-1.036), P = 0.012.. EPO levels higher than expected, suggesting resistance to the hormone, are common in CHF patients and are associated with a higher mortality.

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Epidemiologic Methods; Erythropoietin; Female; Heart Failure; Humans; Male; Prognosis; Stroke Volume

Topics: Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Heart Failure; Humans; Prognosis

The anemia of inflammation is an acquired disorder affecting patients with a variety of medical conditions, and it is characterized by changes in iron homeostasis and erythropoiesis. Mounting evidence suggests that hepcidin antimicrobial peptide plays a primary role in the pathogenesis of the anemia of inflammation. To evaluate which features of this anemia can be attributed to hepcidin, we have generated mice carrying a tetracycline-regulated hepcidin transgene. Expression of the hepcidin transgene resulted in down-regulation of endogenous hepcidin mRNA. The transgenic mice developed a mild-to-moderate anemia associated with iron deficiency and iron-restricted erythropoiesis. Similar to the anemia of inflammation, iron accumulated in tissue macrophages, whereas a relative paucity of iron was found in the liver. Circulating erythrocytes in transgenic animals had normal survival rates, but transgenic animals had an impaired response to erythropoietin. Thus, hepcidin transgenic mice recapitulate each of the key features of anemia of inflammation in human patients and serve as a useful model of this prevalent disorder.

Topics: Anemia, Iron-Deficiency; Animals; Antimicrobial Cationic Peptides; Cell Survival; Disease Models, Animal; Erythrocytes; Erythropoiesis; Erythropoietin; Hepcidins; Inflammation; Iron; Macrophages; Mice; Mice, Transgenic

There is increasing evidence that the anaemia of surgery is not iron deficient and is, therefore, unresponsive to iron supplementation. Oral iron is best avoided postoperatively, particularly in children, due to its dose-dependent side effects. We undertook a national survey of major paediatric orthopaedic surgical units in the UK to investigate the current management of postoperative anaemia with particular reference to iron supplementation.. Middle-grade doctors and charge nurses at 23 major paediatric orthopaedic units in the UK were contacted by telephone and a structured questionnaire was used to determine the management of postoperative anaemia in major hip, pelvic and spinal surgery.. Only one (4.3%) of the units surveyed had a formally established protocol for the management of postoperative anaemia. Only 10 out of 23 units (43.5%) did not routinely prescribe iron postoperatively. Of the remaining units, 11 commenced iron based on the postoperative haemoglobin level while only 2 used iron supplementation after investigation of serum haematinics for iron deficiency. One unit used erythropoietin in the treatment of postoperative anaemia.. Iron supplementation continues to be used in major paediatric orthopaedic surgery in the treatment of postoperative anaemia in the absence of iron deficiency. Given the current available evidence, we call for an end to the practice of routine iron supplementation for postoperative anaemia following major paediatric orthopaedic surgery in the UK.

Topics: Anemia, Iron-Deficiency; Child; Erythropoietin; Health Care Surveys; Humans; Iron; Orthopedic Procedures; Postoperative Care; Postoperative Complications; Professional Practice; United Kingdom; Vitamin B 12

Topics: Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Humans; Injections, Intravenous; Iron; Recombinant Proteins

Anemia is frequent in cancer patients, is the result of decreased erythropoietin production. In fact in cancer, alteration of immune system alters iron metabolism and inhibits erythropoietin production. In this study we proposed to determine the profile of erythropoietin secretion in anaemic cancer patients in the pre and postoperative period. Our prospective study from January to March 2005 included 41 anemic cancer patients from 30 to 79 years old and 31 healthy individuals with iron deficiency anemia. A measure of erythropoietin, CRP, ferritin, iron levels and hemoglobin were released in healthy individuals and in cancer patients in preoperative period (J0) and postoperative period (J3, J8, J21). In preoperative period, the increase of serum erythropoietin was significantly lower in patients than in healthy individuals. In postoperative period, the levels of erythropoietin at J3 and hemoglobin's at J8 and J21 were significantly higher than in preoperative period (J0) (p < 0.05). In conclusion, despite the presence of inflammatory syndrome caused by surgery, cancer patients with anaemia increase their erythropoietin production in immediate postoperative period.

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Digestive System Neoplasms; Erythropoietin; Female; Ferritins; Genital Neoplasms, Female; Hemoglobin A; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Time Factors

Human recombinant erythropoietin (rHuEPO) is widely used to stimulate red blood cell production in patients with anemia due to cancer, renal disease, and other medical conditions, but concern has grown about its overuse and potential for harm. Little is known about the nature of rHuEPO use in hospitalized patients who receive rHuEPO therapy for nononcologic indications.. We reviewed the drug utilization data from a large academic medical center for all patients admitted during 3 years to identify all patients without cancer who received at least 1 dose of rHuEPO, including their age and sex; diagnoses; hematocrit and hemoglobin and iron levels; and use of supplemental iron. We also compared the rates of laboratory testing and iron supplementation in patients with and without chronic kidney disease (CKD).. A total of 1360 distinct patients with 3094 hospitalizations received at least 1 dose of rHuEPO. In 2959 admissions for which hematocrit was determined within 14 days before rHuEPO use, mean values were less than 33% in 1792 (61%) and greater than 36% in 553 (19%). Patients with CKD were more likely than patients without CKD to receive rHuEPO with hematocrit greater than 36% (22% vs 8%; P<.001). Monitoring of iron status was more common in patients with CKD than in those without CKD (64% vs 45%; P <.001). Almost one fourth (23%) of rHuEPO recipients in whom iron levels were measured had absolute iron deficiency (serum ferritin concentration <100 ng/mL). In patients with CKD, only about half (54%) had adequate iron stores at the time of rHuEPO administration; this rate was even lower in patients without CKD (33%; P<.001). Only 66% of patients with documented iron deficiency who were receiving rHuEPO also received concomitant iron supplementation; this rate did not differ between patients with or without CKD.. There is significant variability in the degree of anemia, completeness of iron measurement, and use of iron supplementation in hospitalized patients without cancer who are prescribed rHuEPO. Our results identify potential targets for quality improvement in patients both with and without CKD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Drug Utilization Review; Erythropoietin; Female; Hematocrit; Humans; Inpatients; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

We conducted this study to determine the achievements of the current practice guidelines in the management of anemia in the Arabian Gulf Countries. The survey was designed as a retrospective, one day screening of adult patients with end-stage renal disease in six Arabian Gulf countries including Saudi Arabia, Kuwait, Bahrain, Oman, United Arab Emirates and Qatar. Data were collected on patients undergoing chronic dialysis. For random patient sampling, each participating center drew up an alphabetical list of all hemodialysis (HD) or peritoneal dialysis (PD) patients which were 18 years or older and selected every fourth patient on the list. A total of 563 patients from 18 centers were included in the survey. The most common cause of end-stage renal failure was diabetic nephropathy, closely followed by chronic glomerulonephritis. The majority of patients were treated by HD, with only 20% receiving PD. The mean (+/-SD) hemoglobin (Hgb) concentration was 115 +/- 15 g/L (median, 115 g/L; range, 61-159 g/L). The Hgb concentration was > or = 110 g/L in 28%, > or = 120 g/L in 38% and < 100 g/L in 16%. Information on their iron status was available for 97% of patients, ferritin levels were available for 97% and TSAT values for 67% were available. The mean serum ferritin concentration for the study patients was 503 +/- 406 ng/ml (median, 390 ng/ml; range, 20.0-2960 ng/ml); 90.5% had a serum ferritin concentration > 100 ng/ml. We conclude that the results of our study demonstrate anemia management in the Gulf countries which is comparable to the European Survey on Anemia Management 2003 (ESAM 2003). However, many patients still have not reached the current recommendation of anemia management.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Bahrain; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Kuwait; Male; Middle Aged; Oman; Population Surveillance; Prognosis; Qatar; Renal Dialysis; Retrospective Studies; Saudi Arabia; United Arab Emirates

An 18-year-old woman patient was discovered to have severe anemia and advanced renal failure during a routine prenatal follow-up at her 6th week of gestation. During the first few weeks of therapy, the hemodialysis frequency was increased gradually and Erythropoietin was administered with intravenous iron therapy to keep the patient's hemoglobin above 115 gm/L. Blood pressure rose was controlled by alpha methyldopa. Obstetric follow-up consisted of monitoring the fetal activity and growth, placental maturity and umbilical artery perfusion. On the 32nd week of gestation, the patient had a normal vaginal delivery of live female weighing 2,100 gm. the patient had a completely uneventful postpartum course and the newborn baby was well. In conclusion, our index case illustrates that intensified dialysis regimens and attentive medical care results in a successful outcome of pregnancy in patients with end stage renal disease on hemodialysis.

Topics: Adolescent; Anemia, Iron-Deficiency; Erythropoietin; Female; Follow-Up Studies; Humans; Infant, Newborn; Iraq; Iron; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Renal Dialysis; Renal Insufficiency

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/ epoetin alfa) in severe cases. Iron saccharate (VENOFER) is commercially available in Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

Topics: Anemia, Iron-Deficiency; Biomarkers; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Pregnancy; Pregnancy Complications, Hematologic; Recombinant Proteins; Sucrose; Switzerland; Transferrin

This study was undertaken to assess the safety and tolerability of the use of intravenous (IV) iron sucrose in the therapy of iron-deficiency anemia in elderly, hemodialysis dependent (HDD), chronic kidney disease (CKD) patients.. This was a multicenter, open-label study in a large consecutive sample of 665 HDD-CKD patients (in 11 locations). Patients received IV iron sucrose therapy in treatment and maintenance dosing cycles over 10-week periods. There were 10 doses of 100 mg of iron sucrose in each drug cycle, and participants could receive multiple cycles of either or both regimens. Variables evaluated in the intent-to-treat population included adverse events (AEs), hemoglobin, and iron indices.. Of the 665 patients, 391 patients were under the age of 65 (younger adults) and 274 were 65 years of age or older (elder adults). Iron needs and erythropoietin dosing were similar in both the elder and younger adult patients. The incidence, severity, and nature of AEs and overall mortality were similar in both age groups. There were no drug-related deaths or drug-related serious AEs in either group. There were no hypersensitivity reactions or allergic reactions in either patient population, even among those with a prior history of intolerance to other parenteral-iron products. Comparison of the two age groups also revealed no differences in the efficacy of iron treatment as reflected by hemoglobin, transferring saturation, and ferritin response.. There is no apparent difference in the safety and efficacy of iron sucrose between elder and younger adults in the treatment of iron-deficiency anemia in HDD patients with CKD.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Geriatrics; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

On the basis of follow up of 462 adolescent girls of 14-19 years old, in 110 of them iron-deficiency anemia was revealed. With the help of general blood analysis and biochemistry studies there was detected a disturbance of iron metabolism, declaring itself in decreasing iron serum indices, serum ferritin saturation factor and increase of general iron combined ability levels, latent combined ability and levels of serum erythropoietin.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Humans; Iron; Kinetics; Transferrin

Chronic lung disorders are usually associated with a hypoxia driven increase in red cell mass. However, patients with cystic fibrosis (CF) often have normal or decreased haemoglobin levels. The present prospective observational study in cystic fibrosis patients was performed to determine which factors were involved in alterations in the hematopoetic response to corresponding arterial oxygen pressure. Sixty adult patients (age 21-51) with stable CF were included. They all had vitamin A, D, E, and K but no vitamin B12 supplementation. Twenty-five patients were on oral Fe(2+) (100 mg/day). Resting arterial blood gases, lung function, complete blood counts, parameters of iron status, CRP, sputum microbiology and serum erythropoietin were measured at recruitment and after 3 and 6 months. Patients had varying degrees of pulmonary functional impairment and 9% were hypoxemic (arterial oxygen pressure <60 mm Hg). Low-grade systemic inflammation (CRP > 0.5 mg/dl) was present in 40% of the patients, who all had bacterial colonization. None of the patient had erythrocytosis and 12 patients had anemia. There was no significant difference in iron status between patients with or without chronic iron supplementation and erythropoietin levels were normal. During the 6 months observation period no significant changes occurred. The patients exhibited an impaired erythropoietic response to hypoxemia with normal or low hematocrit in spite of chronic lung disease which might be caused by chronic inflammation associated with CF. Linear multivariate regression analysis revealed CRP levels but neither iron substitution, nor erythropoietin levels nor lung function parameters as independent determinant of haemoglobin levels. CF may be associated with anemia of variable severity as expression of the chronic inflammation present in these patients. The therapeutic consequences are to treat the underlying inflammation rather than to supplement iron.

Topics: Adult; Anemia, Iron-Deficiency; Blood Gas Analysis; C-Reactive Protein; Cystic Fibrosis; Erythropoietin; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Hemoglobins; Humans; Male; Middle Aged; Oxygen; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Heart Failure; Hematinics; Humans; Infusions, Intravenous; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Erythropoietin; Heart Failure; Humans; Iron Compounds; Length of Stay; Prevalence; Prognosis; Sleep Apnea Syndromes; Survival Rate

Central sleep apnea (CSA) (with or without Cheyne-Stokes breathing) or obstructive sleep apnea (OSA) are common in congestive heart failure (CHF). Correction of anemia may improve CHF. We hypothesized that correction of anemia might also improve sleep-related breathing disorders (SRBDs) in CHF.. Thirty-eight patients with CHF and anemia (hemoglobin level < 12 g/dL) were treated with erythropoietin and intravenous iron to a target hemoglobin level of 13 g/dL. Home sleep recordings were done before and after 3 months of treatment.. Thirty-seven patients had SRBD (Apnea Hypopnea Index [AHI] of > or = 10). Hemoglobin level increased from 10.4 +/- 0.8 to 12.3 +/- 1.2 g/dL (P < .001). Total AHI values decreased from 35.9 +/- 12.2 to 24.9 +/- 12.2 (P < .001). The AHI of CSA, OSA and Cheyne-Stokes breathing decreased from 26.5 +/- 14.6 to 18.6 +/- 7.7, from 9.4 +/- 10.9 to 6.9 +/- 9.8, and from 13.1 +/- 16.4 to 9.0 +/- 12.2, respectively (all P < .05). Sleep minimal oxygen saturation (SaO2) increased from 62% +/- 12% to 71% +/- 11%; Epworth Sleepiness Scale score improved from 9.4 +/- 6.2 to 6.0 +/- 5.0 and New York Heart Association class improved from 2.9 +/- 0.4 to 1.7 +/- 0.7, all P < .001. Hemoglobin level improvement correlated with improvement in OSA+CSA, CSA, minimal SaO2, Epworth Sleepiness Scale score, and New York Heart Association class (all P < .001).. Improvement of anemia in CHF is associated with a reduction in SRBD and an improvement in daytime sleepiness.

Topics: Aged; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferritins; Follow-Up Studies; Heart Failure; Hematinics; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Polysomnography; Retrospective Studies; Sleep; Sleep Apnea Syndromes; Treatment Outcome

First experience of application of the blood autodonorship programme, using recombinant erythropoietin (Eprex) plus preparations containing iron during their preparation for partial hepatic resection, was analyzed. Realization of this programme had permitted to escape the performance of allogenic hemotransfusion in 71.4% of donors, in whom the right or left hepatic lobe was taken out and in 100%--the left lateral section. The erythropoietin dosage regimes in different types of hepatic resections in living kindred donors were proposed.

Topics: Adult; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Family; Female; Humans; Liver Transplantation; Living Donors; Male; Middle Aged; Recombinant Proteins

Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy.. We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth.. At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by approximately 90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points.. HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

Topics: Anemia, Iron-Deficiency; Cohort Studies; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; HIV Seronegativity; HIV Seropositivity; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Odds Ratio; Receptors, Transferrin; Risk Factors; Zimbabwe

Anemia is as a frequent complication in patients with chronic kidney disease, which gains in importance in the treatment of patients with renal disease. The main cause of renal anemia is the inadequately low production of endogenous erythropoietin. Often the patients develop an additional absolute or functional iron deficiency, which complicates the diagnostic and therapeutic procedures. Substitution of recombinant human erythropoietin (r-HuEPO) is the most effective therapy. The goal is a stable haemoglobin level >11 g/dl. An often additional existing iron deficiency should be balanced adequately according to the guidelines. With consequent and early treatment morbidity, mortality, and quality of life can be effectively improved.

Topics: Anemia; Anemia, Iron-Deficiency; Diagnosis, Differential; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Glomerular Filtration Rate; Humans; Inflammation Mediators; Iron Compounds; Kidney Failure, Chronic; Kidney Function Tests; Recombinant Proteins; Treatment Outcome

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/Epoetin alfa) in severe cases. Iron saccharate Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

Topics: Administration, Oral; Adult; Age Factors; Aged; Anemia, Iron-Deficiency; Cross-Sectional Studies; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobinometry; Humans; Infant, Newborn; Infusions, Intravenous; Iron Compounds; Male; Middle Aged; Nutritional Requirements; Pregnancy; Risk Factors; Transferrin

The diagnostic power of the transferrin receptor-ferritin (TfR-F) index for identification of iron responsiveness in long-term hemodialysis (HD) patients compared with the routine markers recommended by the current US and European guidelines was appraised.. Initially, 121 long-term HD patients with a serum ferritin level less than 800 microg/L and on recombinant erythropoietin (rHuEPO) therapy for longer than 6 months were enrolled for intravenous iron (IVFE) supplementation (100 mg of iron polymaltose 3 times/wk for 4 weeks, then 100 mg every 2 weeks for 5 months). Routine iron tests (ie, serum ferritin and transferrin saturation [TSAT]), TfR-F index calculated by the ratio of soluble TfR to log ferritin level, hematocrit, hemoglobin, red blood cell count, and serum high-sensitive C-reactive protein were examined at baseline. Hematocrit and hemoglobin were followed up every 2 weeks during the study period.. One hundred patients (52 men, 48 women; mean age, 59 years) completed this study. Fifty-two patients were IVFE responders, defined as an increase in hematocrit greater than 3% and/or a decrease in rHuEPO dose greater than 30% of baseline values at the end of the study, and 48 nonresponders did not fulfill these criteria. Of 52 responders, only 14 patients (27%) could be recognized for iron deficiency by means of routine iron tests (ferritin < 100 microg/L and/or TSAT < 20%). Thirty-three responders (63%) could be further identified for iron deficiency by using TfR-F index (> 0.6), but 5 (10%) still could not by either method. Analyses by using receiver operating characteristic (ROC) curves showed that a cutoff value greater than 0.6 for TfR-F index had greater sensitivity (90%) for the detection of iron deficiency than ferritin level less than 100 microg/L (29%) and TSAT less than 20% (6%). TfR-F index showed a greater area under the ROC curve than ferritin level (P < 0.05) and TSAT (P < 0.001).. TfR-F index is superior to routine tests for predicting response to IVFE supplementation in long-term HD patients. Our study indicates that TfR-F index is a new and surrogate marker to estimate body iron stores and guide IVFE therapy for long-term HD patients.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Biomarkers; Biopsy; Bone Marrow; C-Reactive Protein; Diagnostic Tests, Routine; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Receptors, Transferrin; Renal Dialysis; Sensitivity and Specificity; Time Factors

Topics: Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Ferritins; Hematocrit; Hemoglobins; Humans; Injections, Intravenous; Iron; Recombinant Proteins; Renal Dialysis

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Direct measurement of the reticulocyte hemoglobin content provides useful information for the diagnosis and treatment of iron-deficient states. We have examined direct measurements of reticulocyte and red cell hemoglobin content on the Sysmex XE 2100 (Ret He and RBC He respectively) and the Bayer ADVIA 2120 (CHr and CH respectively) analyzers. Good agreement was found between Ret He and CHr (Y = 1.04X - 1.06; r2= 0.88) and between the RBC He and CH parameters (Y = 0.93X + 1; r2= 0.84 n = 200) in pediatric patients and in normal adults (Ret He and CHr; Y = 1.06X - 0.43; r2= 0.83; n = 126; RBC He and CH; Y = 0.94X + 1; r2= 0.87; n = 126). In 1500 blood samples from patients on chronic dialysis, Ret He was compared with traditional parameters for iron deficiency (serum iron <40 microg/dl, Tsat <20%, ferritin <100 ng/ml, hemoglobin <11 g/dl) for identifying iron-deficient states. Receiver operator characteristic (ROC) curve analysis revealed values of the area under the curve for Ret He of 0.913 (P < 0.0001). With a Ret He cutoff level of 27.2 pg, iron deficiency could be diagnosed with a sensitivity of 93.3%, and a specificity of 83.2%. Ret He is a reliable marker of cellular hemoglobin content and can be used to identify the presence of iron-deficient states.

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Dialysis; Erythropoietin; Female; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Reference Values; Reproducibility of Results; Reticulocytes; ROC Curve; Sensitivity and Specificity

Anemia is common following liver transplantation. Because cyclosporine inhibits erythropoietin (Epo) production in experimental models, we investigated whether Epo production was impaired in liver transplant recipients receiving a cyclosporine- or tacrolimus-based immunosuppressive regimen. First, serum Epo levels were measured before and 1 year after transplantation in 35 liver transplant recipients. Second, serum Epo levels were compared in a large series of liver transplant recipients with stable graft and renal functions: 27 receiving a cyclosporine-based and 31 receiving a tacrolimus-based immunosuppressive regimen. A reference group was made up of 22 blood donors and 21 nontransplanted subjects with iron-deficiency anemia. Serum Epo levels were significantly lower after than before liver transplantation, especially in cyclosporine-treated patients. Serum Epo concentrations correlated with hematocrit values in both transplant recipients and control subjects. Using multiple linear regression models, the polynomial relationship between hematocrit and serum Epo values was similar to the control group in patients under tacrolimus, whereas Epo production was significantly reduced in patients under cyclosporine-based immunosuppression. Hematocrit values and the type of calcineurin inhibitor were the only parameters independently related to Epo levels. In conclusion, cyclosporine, but not tacrolimus, inhibits Epo production at the doses used in clinical practice.

Topics: Adult; Anemia, Iron-Deficiency; Blood Donors; Calcineurin Inhibitors; Cyclosporine; Erythropoietin; Female; Hematocrit; Humans; Immunosuppressive Agents; Linear Models; Liver Transplantation; Male; Middle Aged; Osmolar Concentration; Postoperative Period; Preoperative Care; Tacrolimus

The prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients. All new hemodialysis patients entering a single hemodialysis unit between July 1999 and April 2002 were included in the study. The admission laboratory tests and the Health Care Financing Administration (HCFA) 2728 form were examined to determine the prevalence of erythropoietin use, anemia (Hb<11 g/dl), and iron deficiency (ferritin<100 ng/ml and transferrin saturation %<20%). In a second part of the study, the effect of intravenous iron gluconate replacement in patients with stage III & IV chronic kidney disease was examined. Anemia was present in 68% of all patients starting hemodialysis. Iron deficiency was a common feature occurring in 29% of patients taking erythropoietin (49% of all patients) and 26% of patients without erythropoietin (51% of all patients). Following the administration of intravenous iron gluconate to four patients, there was a significant rise in hemoglobin levels from 10.6+/-0.19 to 11.7+/-g/dl (p=0.02).. Iron deficiency is common in predialysis patients. Replenishing iron stores in anemic patients with chronic kidney disease significantly increases hemoglobin levels and should be considered as an integral part of the therapy for treating anemia in the predialysis population.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Ferric Compounds; Gluconates; Humans; Kidney Diseases

To study whether hematologic malignancy patients with anemia have a lower erythropoietin (EPO) response.. Serum EPO levels were detected by ELISA in patients with hematologic malignancies and with iron deficiency anemia (IDA). Eighty patients with hematologic malignancies, including 13 multiple myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty patients with IDA were studied as the control.. Hematologic malignancy patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA, serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) , but no such inverse correlation was found in the hematologic malignancy patients with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were significantly lower in anemic patients with hematologic malignancies than in IDA patients (P = 0.032) , indicating a decreased EPO response in the former group.. Anemia associated with hematologic malignancy might result from an inappropriately low EPO response. EPO treatment for these patients may be beneficial.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies

Many studies in the general population have shown a link between Helicobacter pylori infection and iron-deficiency, often resulting in iron-deficient anaemia. Despite the high prevalence of iron deficiency in hemodialysis patients, no studies have been performed in this population.. To evaluate the role of Helicobacter pylori infection in the appearance of anemia and the iron requirements in our hemodialysis population.. After excluding patients with severe pathology and short life expectancy and those with blood losses secondary to other causes, 79 patients were included.Iron requirements and anaemia were determined by iron serum, ferritin, and hematocrit values; and by transfusion, eritropoietin and iron requirements. The diagnosis of Helicobacter pylori status was established by the concordance of at least two of the three non invasive diagnostic methods performed (breath test, serology and fecal antigen of Helicobacter pylori).. Prevalence of Helicobacter pylori infection was 43%. No significant differences between patients infected or not by Helicobacter pylori were found in any of the variables analysed: hematocrit (33.5% versus 34.1%), serum iron (58.9 versus 63.7 pg/dl), ferritin(340.3 versus 264.2 ng/ml), transferrin saturation index (22.5% versus 25.2%), dose of eritropoietin administered (96.6 versus 93.5 U/kg/weekly), and parenteral iron (1,389 versus 1,538 mg/year). A noteworthy finding was that patients with Helicobacter pylori infection had been on hemodialysis for a shorter period than those without (37.4 versus 63.7 months,p = 0.04).. Helicobacter pylori infection has no effect on anaemia (hematocrit, Eritropoietin dose or iron needs) in our hemodialysis patients. Prevalence of Helicobacter pylori is lower in patients with longer time on dialysis. We consider that the diagnosis of Helicobacter pylori infection must be reserved for clinical peptic ulcer suspicion or patients on transplant waiting list.

Topics: Aged; Anemia, Iron-Deficiency; Comorbidity; Dyspepsia; Erythropoietin; Female; Ferritins; Helicobacter Infections; Helicobacter pylori; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Hematinics; Humans; Infusions, Intravenous; Iron Compounds; Practice Guidelines as Topic; Quality of Health Care; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF).. We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n=211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA).. The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month.. CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.

Topics: Anemia, Iron-Deficiency; Disease Progression; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Reticulocytes

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.

Topics: Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Cisplatin; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms

Anemia in pregnancy is seen often because of iron deficiency and the "physiologic dilution" that occurs in the third trimester. Other causes include genetic conditions, such as sickle cell anemia and thalassemias. In cases not responding to iron therapy, patients occasionally require a blood transfusion to restore adequate circulating red blood cell mass. In patients belonging to the Jehovah's Witness sect, transfusion of blood products is not allowed, and treatment of anemia in pregnancy may require use of erythropoietin.. A 26-year-old, African American woman belonging to the Jehovah's Witness sect presented with anemia associated with beta-thalassemia. Iron therapy and prenatal vitamins did not correct the anemia, and the patient became symptomatic, with fatigue and shortness of breath when walking. Therapy with synthetic erythropoietin corrected the anemia, and the patient had an otherwise-uncomplicated pregnancy and delivery.. Synthetic erythropoietin has been used successfully in patients with renal failure and anemia. In pregnancy associated with renal failure and anemia, synthetic erythropoietin has been shown to be safe except for rare cases of hypertension. We treated anemia caused by beta-thalassemia in pregnancy with synthetic erythropoietin to avoid a transfusion in a Jehovah's Witness.

Topics: Adult; Anemia, Iron-Deficiency; beta-Thalassemia; Erythropoietin; Female; Follow-Up Studies; Gestational Age; Humans; Jehovah's Witnesses; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Risk Assessment; Treatment Outcome

Pregnant women often develop anemia concomitant with the increase in serum erythropoietin levels, which are actually lower than those of nonpregnant anemic women due to the possible suppressive effect of endogenous estradiol on erythropoietin induction. The anemia, derived from hemodilution, does not act as a drive for erythropoietin induction, but iron deficiency, often observed during pregnancy, might. In order to demonstrate this, we investigated the effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats. Single doses of estradiol suppressed hypoxia-, cobalt-, and bleeding-stimulated elevation of plasma erythropoietin levels and renal erythropoietin mRNA expression. Repeated administration of estradiol at 0.1 and 1 mg/kg for 2 months induced a slight anemic trend without elevation of plasma erythropoietin. Feeding an iron-deficient diet for 2 months induced plasma erythropoietin elevation without obvious anemia, but the simultaneous repeated administration of estradiol suppressed it and reversed the iron deficiency. Plasma erythropoietin levels had distinct negative correlations with plasma iron, plasma ferritin, and iron concentrations in the organs, but not with plasma hemoglobin level. These results suggest that iron deficiency would significantly stimulate erythropoietin induction during pregnancy, although estradiol might suppress it through iron restoration.

Topics: Anemia, Iron-Deficiency; Animal Feed; Animals; Disease Models, Animal; Erythropoiesis; Erythropoietin; Estradiol; Female; Iron; Kidney; Liver; Organ Size; Pregnancy; Pregnancy Complications, Hematologic; Rats; Rats, Wistar

To investigate whether postoperative administration of erythropoietin can safely augment in the rapid restoration of hemoglobin (Hgb) values following major gynecologic surgery.. Thirty-three women were enrolled. They had all undergone gynecologic surgery due to malignant or non-malignant reasons. Because of chronic blood loss, many of these patients were iron depleted. Examinations of hematology, serum chemistry and urinalysis values were obtained. Subcutaneous administration of r-HuEPO, in a dosage of 40,000 IU was initiated on the first postoperative day. One additional injection of 40,000 IU was given on the fourth day after surgery. Contemporarily the patients received orally a polysaccharide-iron complex.. During the early postoperative period three patients that were transfused due to severe anemia and one more that was lost in follow-up were excluded from the study analysis. The remaining 29 patients showed a considerable rise in Hgb counts that reached a median value of 1.9 g/dl within a 20-day period.. The postoperative administration of r-HuEPO in gynecologic surgery in patients where autologous blood transfusions can be avoided is challenging, since it can guarantee an uneventful postoperative period with rapid resuscitation without posing the patient to the well-established risks of transfusions.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Blood Loss, Surgical; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Ferric Compounds; Greece; Gynecologic Surgical Procedures; Hemoglobins; Humans; Injections, Subcutaneous; Menorrhagia; Middle Aged; Polysaccharides; Postoperative Care; Prospective Studies; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Hemoglobins; Humans; Iron; Recombinant Proteins; Uterine Cervical Neoplasms

Anemia is a common problem in critically ill patients. The etiology of anemia of critical illness is often determined to be multifactorial in the clinical setting, but the pathophysiology remains to be elucidated. Erythropoietin (EPO) is an endogenous glycoprotein hormone that serves as the primary stimulus for erythropoiesis. Recent evidence has demonstrated a blunted EPO response as a factor contributing to anemia of critical illness in specific subsets of patients. Critically ill patients requiring mechanical ventilation who exhibit anemia have not been the subject of previous studies. Our goal was to evaluate the erythropoietic response to anemia in the critically ill mechanically ventilated patient.. A prospective observational study was undertaken in the medical intensive care unit of a tertiary care, military hospital. Twenty patients admitted to the medical intensive care unit requiring mechanical ventilation for at least 72 hours were enrolled as study patients. EPO levels and complete blood count were measured 72 hours after admission and initiation of mechanical ventilation. Admission clinical and demographic data were recorded, and patients were followed for the duration of mechanical ventilation. Twenty patients diagnosed with iron deficiency anemia in the outpatient setting were enrolled as a control population. Control patients had baseline complete blood count and iron panel recorded by primary care physicians. EPO levels were measured at the time of enrollment in conjunction with complete blood count.. The mean EPO level for the control population was 60.9 mU/ml. The mean EPO level in the mechanically ventilated patient group was 28.7 mU/ml, which was significantly less than in the control group (P = 0.035). The mean hemoglobin value was not significantly different between groups (10.6 g/dl in mechanically ventilated patients versus 10.2 g/dl in control patients; P > 0.05).. Mechanically ventilated patients demonstrate a blunted EPO response to anemia. Further study of therapies directed at treating anemia of critical illness and evaluating its potential impact on mechanical ventilation outcomes and mortality is warranted.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Case-Control Studies; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Hospitals, Military; Humans; Intensive Care Units; Linear Models; Male; Middle Aged; Prospective Studies; Respiration, Artificial

The percentage of hypochromic erythrocytes (%HYPO) and the reticulocyte hemoglobin content (CHr) have been used for the diagnosis of iron deficiency (ID). However, we found a discrepancy between %HYPO and CHr values in some hemodialysis patients. Hemodialysis patients receiving recombinant human erythropoietin (rHuEPO) with ID were defined as patients with a %HYPO value exceeding 5%. Five ID patients with a high CHr (group A) and 3 ID patients with a low CHr (group B) received 120 mg/week iron intravenously for 8 to 12 weeks. Changes in %HYPO, CHr, percentage of macrocytic erythrocytes (%MACRO), absolute reticulocyte count, immature reticulocyte fraction, and soluble transferrin receptor level were investigated over a 20-week period. CHrs were measured with 2 hematology analyzers: the Bayer HealthCare Technicon H*3 and the ADVIA 120. Patients in group A showed a significantly greater mean %MACRO (P < .01) and a lower mean red blood cell number (P < .05) than patients in group B. Even the mean CHr at baseline in group A was significantly higher than the mean CHr in the healthy subjects (P < .01), and hemoglobin levels increased in association with the reduction in rHuEPO dose following iron administration (P < .01). We found a group with high CHr, %HYPO, and %MACRO values among hemodialysis patients. Iron administration enables the rHuEPO dose to be reduced.

Topics: Anemia, Iron-Deficiency; Case-Control Studies; Drug Monitoring; Erythrocytes; Erythropoietin; Hematologic Tests; Hemoglobins; Humans; Iron; Recombinant Proteins; Renal Dialysis; Renal Insufficiency; Reticulocytes

Unlike iron therapy, folate use is not a standard of care in hemodialysis (HD) patients. Despite iron repletion, poor response to erythropoietin (EPO) treatment is common. Theoretical evidence for folate deficiency (FD) includes chronic blood loss, inflammation, malnutrition, and nutrient loss during dialysis. Due to poor diagnostic standards, early studies failed to establish a role for FD in EPO resistance. Given that hematological response to therapeutic intervention is the gold standard for FD, its diagnosis was therefore based on composite scoring of RBC and/or folate indices. Fifteen subjects (8-20 years) on chronic HD were enrolled in this study. No folate supplement was given in the first six months. Thereafter, 5-mg folic acid was administered orally after HD sessions over a six-month period. Folate indices before and after treatment were compared using percentage differences and paired t-tests. After folate use, the mean Hb increased by 11.4%, while MCV and RDW were reduced. Similarly, 4 of the 15 subjects each had a > or = 20% rise in Hb and a > or = 5% reduction in MCV, while 46.7% had a > or = 2.5% reduction in RDW. Mean RBC folate increased by 24%, while FD scores reduced from 3.8+/-1.2 to 0.4+/-0.7, and the EPO requirement by 90%. In contrast to previous studies, 26.7% of study subjects met the criteria for FD. Furthermore, the substantial (post-folate) reduction in the EPO requirement validates the need for therapeutic intervention, and therefore the presence of functional FD in the population.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Child; Drug Resistance; Erythropoietin; Female; Folic Acid; Folic Acid Deficiency; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Vitamin B 12

Anemia is prevalent among pregnant adolescents, but few data exist on biochemical indicators of iron status in this group. We hypothesized that among an at-risk population of African-American, pregnant adolescents, the degree of iron depletion and deficiency would be marked, and that iron deficiency anemia would comprise the majority of the observed anemia. To examine this, blood samples were collected from 80 girls (< or =18 y old) attending an inner city maternity clinic, 23 of whom were studied longitudinally in the 2nd and 3rd trimesters depending on contact at the clinic. Sample sizes for the biomarkers varied according to the blood volume available at the time the assays were completed. Descriptive statistics were applied to characterize iron status, and multivariate regression and logistic analyses were used to identify significant determinants of iron status. Depleted iron stores (ferritin < or = 15 microg/L) were indicated for 25% (n = 44) and 61% (n = 59) of adolescents during the 2nd and 3rd trimesters, respectively. Serum folate (39.3 +/- 15.4 nmol/L, n = 60), RBC folate (2378 +/- 971 nmol/L, n = 60), and serum vitamin B-12 concentrations (313 +/- 163 pmol/L, n = 60) were within normal ranges. Adolescents with serum transferrin receptor:serum ferritin ratios (R:F ratio) > 300 during the 2nd trimester were 12.5 times (95% CI 2.83, 55.25) more likely to be classified with iron deficiency anemia during the 3rd trimester (P = 0.0002) than those with lower ratios. Estimates of body iron were lower in those tested after wk 26 of gestation (P < 0.0001), and reserves were depleted in 5.0% vs. 31.3% of the 2nd (n = 40) and 3rd (n = 48) trimester cohorts, respectively. In conclusion, iron-deficiency anemia was prevalent among these pregnant minority adolescents. Targeted screening and interventions to improve diet and compliance with prenatal iron supplementation are warranted for this at-risk group.

Topics: Adolescent; Anemia, Iron-Deficiency; Birth Weight; Black or African American; Body Mass Index; Erythropoietin; Female; Ferritins; Folic Acid; Gestational Age; Hemoglobins; Humans; Iron; Iron Deficiencies; Leptin; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence; Regression Analysis; Transferrin; Vitamin B 12; Weight Gain

Although a known cardiovascular risk factor, anemia in the renal transplant recipients has only recently been receiving an increasing attention.. In a cross-sectional study, data was obtained from 959 patients followed at a single outpatient transplant clinic. Based on the guideline of the American Society of Transplantation, anemia was defined as hemoglobin (Hb) < or =130 g/L in males and < or =120 g/L in females.. About one-third (34%) of the patients were anemic. The prevalence of anemia was comparable in males and females. Serum Hb concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (abbreviated modification of diet in renal disease formula) (r = 0.266, p < 0.001), serum transferrin (r = 0.268, p < 0.001) and serum albumin (r = 0.196, p < 0.001). None of the immunosuppressive medications or the use of angiotensin converting enzyme inhibitors was associated with a higher likelihood of anemia. In multivariate analysis the eGFR, serum albumin and serum transferrin, potential markers of nutritional status and/or chronic inflammation, and also iron deficiency were independently and significantly associated with anemia. Erythropoietin was administered only to 63 (19%) anemic patients.. Post-transplant anemia is a prevalent and under-treated condition. Based on our results we suggest that, besides other factors, protein/energy malnutrition and/or chronic inflammation may be independently associated with anemia. Further studies are needed to determine whether the presence of anemia and its treatment will have an impact on long-term outcomes of this population.

Topics: Adult; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Cross-Sectional Studies; Erythropoietin; Female; Humans; Inflammation; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Protein-Energy Malnutrition; Recombinant Proteins; Transferrin

Women carrying triplets are at greater risk for both anemia, due to the increased demands of the developingfetuses, and peripartum hemorrhage. Jehovah's witnesses are a unique obstetric population since women of this faith refuse blood transfusion.. A Jehovah's Witness with a triplet pregnancy was successfully administered recombinant human erythropoietin (rHuEpo), 200 IU/kg 3 times per week subcutaneously, in order to correct her peripartum anemia. No side effects were observed during rHuEpo therapy, and the patient delivered healthy triplets.. rHuEpo can be safely administered, with a beneficial effect in pregnancy, and seems to be an effective option in preventing transfusions as demonstrated in this case in a Jehovah's Witness.

Topics: Adult; Anemia, Iron-Deficiency; Blood Transfusion; Erythropoietin; Female; Humans; Jehovah's Witnesses; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Triplets

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Child; Child, Preschool; Cross-Sectional Studies; Erythropoietin; Female; Graft Rejection; Growth; Hemoglobins; Humans; Immunosuppressive Agents; Iron; Kidney Function Tests; Kidney Transplantation; Male; Mycophenolic Acid; Recombinant Proteins; Tacrolimus

Topics: Anemia, Iron-Deficiency; Darbepoetin alfa; Erythrocyte Indices; Erythrocyte Transfusion; Erythropoietin; Ferritins; Hemochromatosis; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Phlebotomy; Reticulocyte Count

To investigate the serum erythropoietin (Epo) levels in patients with chronic liver diseases and to compare to subjects with iron-deficiency anaemia and healthy controls.. We examined 31 anaemic (ALC) and 22 non-anaemic (NALC) cirrhotic patients, 21 non- anaemic subjects with chronic active hepatitis (CAH), 24 patients with iron-deficiency anaemia (ID) and 15 healthy controls. Circulating Epo levels (ELISA; R and D Systems, Europe Ltd, Abingdon, UK) and haemoglobin (Hb) concentration were determined in all subjects.. Mean+/-SD of Epo values was 26.9+/-10.8 mU/mL in ALC patients, 12.5+/-8.0 mU/mL in NALC subjects, 11.6+/-6.3 mU/mL in CAH patients, 56.4+/-12.7 mU/mL in the cases of ID and 9.3+/-2.6 mU/mL in controls. No significant difference (P>0.05) was found in Epo levels between controls, CAH and NALC patients. ALC individuals had higher Epo levels (P<0.01) than these groups whereas ID subjects had even higher levels (P<0.001) than patients suffering from ALC.. Increased Epo values in cirrhotics, are only detectable when haemoglobin was lesser than 12 g/dL. Nevertheless, this rise in value is lower than that observed in anaemic patients with iron-deficiency and appears blunted and inadequate in comparison to the degree of anaemia.

Topics: Aged; Anemia, Iron-Deficiency; Erythropoietin; Female; Hemoglobins; Hepatitis, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Regression Analysis

Non-haemodialysis renal patients requiring intravenous iron therapy are increasing the pressure on renal units. A new form of iron therapy can dramatically reduce patient visits, but takes longer to administer. Sunday provision of nurse-led clinics has enabled a switch to this new therapy. Cost savings have more than offset the additional nurse-led sessions and eliminated waiting lists for this group.

Topics: Anemia, Iron-Deficiency; Cost Savings; Efficiency, Organizational; England; Erythropoietin; Hemodialysis Units, Hospital; Hospitals, Public; Humans; Infusion Pumps; Iron-Dextran Complex; Kidney Failure, Chronic; Process Assessment, Health Care; Waiting Lists; Workload

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease patients. Therefore it is essential that serum ferritin levels should be maintened > 200 micro g/l. Functional iron deficiency occurs with serum ferritin levels > 200 micro g/l and transferrin saturation (TFS) lower than 20 %. The purpose of this study was to determine the efficacy of iron therapy in dialysis patients with serum ferritin levels higher than 200 micro g/l.. A total of 16 stable patients receiving chronic hemodialysis completed a 6-month survey period. Hemodialysis therapy and weekly subcutaneous rhEPO dose remained unchanged. Patients were divided into three groups according to their TFS, with TFS low (<20 %), barely adequate (20 % < TFS < 25 %) or optimal (>30 %). Sodium ferric gluconate complex (62.5 mg iron) was administered once per week intravenous over 10 minutes at the end of the dialysis.. After 3 months, hemoglobin was significantly higher in all groups (10.3 +/- 0.7 g/dl to 12,6 +/- 1.3 g/dl; p < 0,01) with no difference between the three groups and was constant in the following 3 months. Intravenous iron therapy raised ferritin levels significantly after 3 and 6 months: this observation was similar in all groups. The rise in TFS varied between and within the three groups.. Consistent intravenous iron therapy in combination with subcutaneous rhEPO had a rapid effect on the correction of anemia in patients with even optimal serum ferritin levels receiving chronic hemodialysis. There was no difference between patients with low, barely adequate and optimal TFS. It is concluded that there is a need for consistent intravenous iron therapy also in hemodialysis patients with optimal serum ferritin levels to correct anemia.

Topics: Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Bone Marrow; Chronic Disease; Cytokines; Erythropoiesis; Erythropoietin; Hematologic Tests; Humans; Inflammation; Iron; Neoplasms

To investigate the possible benefits of erythroproietin ingestion in patients with various gynecological cancers with proven severe iron deficiency anemia.. Seven patients with gynecological cancer were included in the study. Nadir hematocrit values were found to be 20-24% before the initiation of recombinant human erythropoietin treatment. Initial therapy started at 50 units/kg/dose, three times weekly for a month. The dose was modified according to the rise of hemoglobin after a month's period. The dose was modified according to the rise of hemoglobin after a month's period. If the rise was greater than 2 g/dl the dose was changed to 25 units/kg two times weekly and if it was less than 2 g/dl it was changed to 25 units/kg three times weekly per month. Five patients were simultaneously given erythropoietin therapy and iron supplementation.. We confirmed a rise in the hematocrit values which averaged 0.5-1.5% weekly till the upper limit. Reticulocyte and hematocrit values were higher in the erythropoietin plus iron group (five cases).. In this small series, erythropoietin appeared to be effective in treating severe iron deficiency in gynecologic cancer patients. Further investigation is needed to confirm these results.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Female; Genital Neoplasms, Female; Hematocrit; Humans; Injections, Subcutaneous; Recombinant Proteins; Treatment Outcome

Iron deficiency anaemia and the thalassemia syndromes, a group of disorders resulting from inherited abnormality of globin chain production, are common causes of anaemia in Thailand, and in the Far East in general. Monitoring erythropoiesis in these patient is very important in evaluating the disease and the response to treatment. Recently, our group has just reported the feasibility in using serum erythropoietin (EPO) for monitoring purposes in thalassemia and demonstrated that the determination of serum EPO can be an alternative choice in the follow up of these conditions. This study reports a cost effectiveness analysis comparing the recently reported radioimmunoassay (RIA) for serum EPO determination and the previously used tool, the reticulocyte count. The study reports a higher detection rate for ineffective erythropoiesis when using serum EPO determination, however, the increased sensitivity is at balanced by a higher unit cost. In this analysis, the cost effectiveness for serum EPO and reticulocyte are 208.33 and 50 baht/detection, respectively. () Therefore, the reticulocyte count is more cost effective and is recommended for routine usage in our current medico-economic setting.

Topics: Anemia, Iron-Deficiency; beta-Thalassemia; Cost-Benefit Analysis; Erythropoiesis; Erythropoietin; Hemoglobin E; Humans; Monitoring, Physiologic; Radioimmunoassay; Reticulocyte Count; Thailand

Recombinant human erythropoietin (epoetin) is widely used for the treatment of renal anemia. The aim of our study was to determine the influence of epoetin on erythrocyte metabolism. Thirty-six hemodialysis patients (22 men, 14 female), aged from 17 to 64 years (mean age 43) and 30 healthy volunteers (12 men, 18 female), aged from 25 to 65 years (mean age 40) were studied. Epoetin (Eprex, Janssen-Cilag) was administered subcutaneously with the starting dose of 2000 IU three times per week for twelve months (range from 75 to 133 IU/kg/week, mean dose 102+/-21 IU/kg/week). Laboratory markers of: hematological response, iron status and erythrocyte metabolism were measured before epoetin administration. Afterwards the markers were controlled every three months. During epoetin treatment a significant increase in hemoglobin concentration was observed (100% patients responded in a positive way to epoetin). The following changes in erythrocyte metabolism were noticed: 1) in glycolytic enzymes: a significant increase in the activity of hexokinase and that of lactate dehydrogenase, 2) in glycolytic intermediates: a significant increase in the 2,3-diphosphoglycerate and adenosine triphosphate concentrations, 3) a significant increase sodium, potassium adenosine triphosphatase concentration, 4) the glucose uptake by erythrocytes significantly decreased while the lactate production remained stable. During anemia treatment with epoetin in hemodialysis patients not only quantitative but also qualitative changes in erythrocytes were observed.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anemia, Iron-Deficiency; Case-Control Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Reference Values; Renal Dialysis; Risk Assessment; Statistics, Nonparametric; Treatment Outcome

To study characteristics of iron deficiency anemia (IDA) in native population of high altitude territories.. 1300 women living in Tien-Shan areas were examined for serum and erythrocytic ferritins (SF and EF), general iron-binding capacity of the serum, transferrin saturation with iron, transferrin, soluble transferrin receptor (TR), erythropoietin (EP), Hb, erythrocytes, erythrocytic indices.. Regulation of erythropoiesis in women living at high altitude is specific, i.e. disagreement between complete depletion of iron (by SF and EF) and normal level of Hb, erythrocytes, EP and TR.. It is suggested that in population living at high altitudes (3000 m above the sea level and higher) long-term adaptation to hypoxia gave rise to an original mechanism of erythropoiesis regulation when all coming iron participates in hemoglobin synthesis without iron deposition. Under hypoxic hypoxia regulation of erythropoiesis is directed to prevention of tissue hypoxia.

Topics: Adaptation, Physiological; Altitude; Anemia, Iron-Deficiency; Erythrocyte Indices; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Ferritins; Humans; Hypoxia; Iron; Kyrgyzstan; Receptors, Transferrin; Transferrin

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic hemodialysis patients. We advocate an initial dosage of 1500 U three times per week. The fifth section deals with the factors refractory to treatment with rHuEPO. If the patient shows an inadequate response to the usage of 9000 U per week, this condition defines the inadequate response to rHuEPO in Japan. Blood transfusion must be avoided where possible. The reasons for this and the adverse effects are interpreted in section six. In the final section, the adverse effects of rHuEPO are listed. A

Topics: Anemia; Anemia, Iron-Deficiency; Blood Transfusion; Diagnosis, Differential; Erythropoietin; Hematocrit; Humans; Iron Overload; Japan; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Societies, Medical; Treatment Failure

Anaemia is the most common haematological complication in patients with malignant diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis of this hypoproliferative, normochromic, normocytic anaemia is complex. Results from clinical studies which evaluate the efficacy of recombinant human erythropoietin (rHuEpo) refer to the possibility that patients with multiple myeloma independently of renal function could have Epo deficiency. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with multiple myeloma in order to define clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 42 patients with multiple myeloma were examined. The control group consisted of 25 patients with iron deficiency anaemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and haemoglobin (Hb) in the control group, as well as from O/PEpo ratio as a measure of the degree of adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferin receptors (sTfR) and Hb in the control group, as well as from O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O -- observed sTfR value, P -- predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with multiple myeloma but preserved renal function, which was not the case in patients with renal insufficiency. 43% of patients without renal insufficiency and 85% of patients with renal insufficiency had inadequate Epo response to anaemia. In both patient groups (with and without renal insufficiency) instead of the expected inverse relationship between Hb and sTfR as in the control group, a positive correlation was found. 76% of patients had inadequate sTfR response to anaemia. There is a positive correlation between O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and O/PsTfR in patients with multiple myeloma are significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production, respectively erythropoietic activity. In conclusio

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Multiple Myeloma; Receptors, Transferrin

Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo.. Sixty-five HD patients with a serum ferritin level of <500 microg/l and on rHuEpo therapy for >6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of >3% and/or a reduction in rHuEpo dose of >30% over the baseline values at the end of the study.. Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P<0.001). This paralleled a statistically significant rise in CHr and HFR (P<0.001). Univariate analyses showed that ferritin (P<0.010) and CHr (P<0.001) at baseline, changes in CHr (DeltaCHr(2W), P<0.001) and HFR (DeltaHFR(2W), P<0.010) at 2 weeks, as well as changes in CHr (DeltaCHr(4W), P<0.001) and HFR (DeltaHFR(4W), P<0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that DeltaCHr(4W) in conjunction with DeltaHFR(4W) exhibited an r(2) value of 0.531 (P<0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that DeltaCHr(4W) at a cut-off value of >1.2 pg and DeltaHFR(4W) of >500/microl were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response to IVFE therapy, with a sensitivity of 96% and a specificity of 100%.. Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect iron-deficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.

Topics: Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fluorescence; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Recombinant Proteins; Renal Dialysis; Reticulocyte Count; Reticulocytes

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Immunosuppressive Agents; Infections; Kidney Transplantation; Liver Failure; Male; Postoperative Complications; Retrospective Studies; Sex Characteristics

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr).. In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer.. Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO.. CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.

Topics: Adult; Anemia, Iron-Deficiency; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reticulocytes; Transferrin

Increasingly, the therapeutic use of hematopoietic growth factors and immunomodulatory agents is under investigation in patients with low-risk myelodysplastic syndrome (MDS). Studies on amifostine therapy-alone or in combination with erythropoietin (EPO)-indicate that long-term treatment is possibly a decisive factor for therapy success. Therefore, we treated an 81-year-old female, transfusion-dependent patient with MDS and refractory anemia (RA) with amifostine and EPO over a period of 2 years. Following a 4-week induction phase of 5 x 500 mg amifostine plus 3 x 10000 IU EPO per week and maintenance therapy of 1 x 500 mg amifostine plus 3 x 10000 IU EPO per week, normal hemoglobin values were reached in week 14. A long-lasting erythroid response could be observed with a reduction of EPO to 2 x 10000 IU and 1 x 10000 IU and, at present, once a week application of amifostine alone (1 x 500 mg). Apart from the 1st week, the treatment was carried out at the outpatient department and was well tolerated by the patient. The patient experienced a good general clinical condition without further need for hospitalization or blood transfusions.

Topics: Aged; Aged, 80 and over; Amifostine; Anemia; Anemia, Iron-Deficiency; Drug Therapy, Combination; Erythropoietin; Female; Humans; Myelodysplastic Syndromes; Radiation-Protective Agents; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Cell Differentiation; Erythropoietin; Humans; Sequence Homology, Amino Acid; Stem Cells; Thrombocytosis; Thrombopoietin

Algorithms that combine scores from multiple blood parameters are demonstrably effective in highlighting recombinant human erythropoietin (rHuEPO) administration, and have been used to deter rHuEPO use by athletes. These models are sensitive to atypical levels of blood parameters encountered during altered states of red cell production. Because hematologic abnormalities can also result in unusual blood profiles, the aim of this study was to document the incidence and magnitude of such abnormalities in an elite athlete population.. We screened blood samples obtained from 413 female and 739 male elite athletes from 12 countries for known hematologic abnormalities, and compared the algorithm scores for these athletes with those of their healthy counterparts. We also established the magnitude of blood parameters required for model scores to exceed cut-offs associated with rHuEPO use.. We found that 0.7% of male and 2.4% of female athletes were iron deficient either with our without anemia. An additional 1.4% of males and 1.0% of females had hemoglobinopathies. On average these athletes' model scores were at or below the score of their healthy counterparts. The greatest influence on our models was hemoglobin concentration. Values of other parameters must exceed normal ranges by a substantial margin in order for model scores to approach levels associated with rHuEPO use.. The hematologic disorders we encountered in elite athletes were not associated with model scores that exceeded the nominal cut-offs that we have previously recommended to delineate rHuEPO use. We did not find any abnormalities among elite endurance athletes that were associated with high model scores.

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Doping in Sports; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Female; Hematologic Diseases; Hematologic Tests; Hemoglobinopathies; Hemoglobins; Humans; Male; Models, Biological; Recombinant Proteins; Reticulocyte Count; Sensitivity and Specificity; Sex Characteristics; Sex Distribution; Sports

We showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status with regard to erythrocytopoiesis in chronic dialysis status. The mean CHr level was 32.3 +/- 2.2 pg in dialysis patients and CHr was significantly correlated with the conventional parameters of iron deficiency. We aimed to utilize the measurement of CHr levels to monitor iron status in clinical practice. We measured CHr, iron parameters, and the intrinsic EPO concentration in non-dialysis CRF patients to clarify the alterations in CHr levels that occur as renal anemia progresses. CRF patients who visited our out-patient clinic (n = 189) were included in the study. Iron deficiency was defined by the transferrin saturation and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). The mean CHr value of the non-dialysis patients (creatinine clearance less than 70 ml/min) was 32.7 pg, which did not differ significantly from that of the dialysis patients. Significant correlations were found between CHr and TSAT (r = 0.032, p < 0.0177), unlike the correlation with intrinsic EPO levels. Overall, 11% of the patients were diagnosed as having iron deficiency. There was a positive correlation between CHr and serum creatinine levels. Non-dialysis CRF patients treated with rHuEPO at the dose of 24,000 U/month showed different CHr levels compared with other patients (less than 24,000 U/month). It is possible that rHuEPO treatment in non-dialysis patients affects iron dynamics. In conclusion, CHr is an easily measurable and reliable marker of iron status in non-dialysis CRF patients. Moreover, the CHr level was also sensitive to iron alternations in non-dialysis CRF patients under rHuEPO treatment. Accordingly, if long-acting EPO is available for non-dialysis CRF patients, the CHr value is likely to be indicative of the need for iron supplementation.

Topics: Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Reticulocytes

To study iron metabolism in patients on programmed hemodialysis (PH) in oral and intravenous administration of iron drugs; to compare clinical and financial results of using such drugs.. A two-stage trial studied iron metabolism in 158 PH patients on replacement therapy with erythropoetin. They received correction of iron deficiency with oral drugs (stage I) and venofer (stage II).. The study of iron metabolism has found its deficiency in 2/3 patients receiving oral iron: absolute (48%) and relative (20%). Administration of venofer led to a 2-fold increase in the number of patients with normal iron metabolism. The target Hb and Ht were achieved in 2.5 times more patients than before venofer treatment. The dose of erythpoetin in such cases was reduced by 40%. Side effects were not observed. The week cost of venofer treatment per patient was lower by 22.5$ than the cost of treatment with oral iron drugs.. Venofer correction of iron deficiency in PH patients is more effective both clinically and financially than use of oral iron preparations.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Drug Costs; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Sucrose; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Platelet Count; Sequence Homology, Amino Acid; Thrombocytosis; Thrombopoietin

Topics: Anemia, Iron-Deficiency; Cross Reactions; Erythropoietin; Humans; Neoplasm Proteins; Proto-Oncogene Proteins; Receptors, Cytokine; Receptors, Thrombopoietin; Sequence Homology, Amino Acid; Thrombocytosis; Thrombopoietin

In the last two decades, the use of erythropoietin for the correction of anemia in hemodialysis patients has been recommended. In Chile, only 10% of hemodialysis patients use erythropoietin, therefore, the correction of iron deficiency must be optimized.. To report the effects of intravenous iron without erythropoietin in the management of anemia in hemodialysis patients.. Retrospective analysis of 42 patients that received intravenous ferrous sacharate in doses of 100 mg/week during 5 weeks and 100 mg bimonthly during six months. These patients did not receive erythropoietin.. Thirty six patients had iron deficiency. Basal ferritin was 137 +/- 22 micrograms/l and increased to 321 +/- 28 micrograms/l after treatment. Packed red cell volume increased from 24 +/- 2% to 29 +/- 3%. No adverse effects were reported.. Iron deficiency is frequent in hemodialyzed patients. Intraveineous iron is safe and effective in the treatment of iron deficiency in these patients.

Topics: Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Humans; Injections, Intravenous; Iron; Male; Renal Dialysis; Retrospective Studies

An increased level of soluble transferrin receptor (sTfR) has been recognized as a useful indicator of iron deficiency, especially in tumour anaemia and in chronic diseases. In cases of erythropoietin substitution, however, it indicates a successful stimulation of erythropoiesis. We report an "unusual" increase in sTfR in a 60-year-old man who suffered from end-stage hypernephroma with extended lung metastases. He showed pulmonal hypertension, polycythaemia and a high serum level of erythropoietin. We assume that, in this case, the increased sTfR originates not only from bone marrow but could be partly contributed also by the malignant tissue of the hypernephroma.

Topics: Anemia, Iron-Deficiency; Biopsy; Bone Marrow; Carcinoma, Renal Cell; Diagnosis, Differential; Erythropoietin; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Proteins; Polycythemia; Receptors, Transferrin

Maternal and fetal serum erythropoietin levels were correlated with hemoglobin, mean corpuscular volume and serum ferritin in a group of anemic pregnant women to evaluate the effect of maternal anemia on fetal erythropoiesis.. Serum erythropoietin, ferritin, hemoglobin and mean corpuscular volume were investigated in 33 pregnant women with anemia, 11 women with normal hematological parameters and in their newborns.. Maternal serum erythropoietin concentration (mean +/- SEM) was significantly higher in the anemic group (145.2 +/- 42.9 mU/ml) as compared to the control group (37.3 +/- 7.6 mU/ml) (p < 0.05). In newborns, all parameters were comparable in both groups except cord serum erythropoietin concentration (mean +/- SEM) which was significantly higher in newborns born to anemic women (43.9 +/- 5.3 mU/ml) than controls (29.4 +/- 3.7 mU/ml) (p < 0.05). In the anemic group, maternal serum erythropoietin was inversely correlated to maternal hemoglobin (r = -0.375, p = 0.03), maternal hemoglobin was inversely correlated to cord serum erythropoietin (r = -0.552, p = 0.001) and maternal ferritin was correlated to fetal ferritin (r = 0.521, p = 0.002).. Although cord hemoglobin and mean corpuscular volume were not affected by maternal anemia, increased cord serum erythropoietin levels related to low maternal hemoglobin levels suggest an induced fetal erythropoiesis in maternal anemia.

Topics: Anemia, Iron-Deficiency; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Female; Ferritins; Fetal Blood; Hemoglobins; Humans; Infant, Newborn; Pregnancy

We hypothesized that intravenous iron will improve hemoglobin (Hgb) concentrations in anemic patients with chronic kidney disease (CKD), and the response would be greater if the underlying erythropoietin deficiency also was treated.. Charts of 58 CKD veterans (glomerular filtration rate < 80 mL/min) administered at least 125 mg of sodium ferric gluconate complex in sucrose (SFGC) during a period of 1 year for the primary outcome of an increase in Hgb level by at least 0.5 g/dL were reviewed.. Mean Hgb level at baseline was 10.5 +/- 1.4 (SD) g/dL (105 +/- 14 g/L) in the 30 patients administered recombinant human erythropoietin (rHuEPO) plus SFGC and 10.1 +/- 1.3 g/dL (101 +/- 13 g/L) in the 28 patients administered SFGC alone (P = not significant). The primary event occurred in 83% of the rHuEPO-plus-SFGC group at 31 days compared with 60% at 62 days in the group administered SFGC alone (P = 0.037, Cox F test). In patients administered SFGC alone, mean maximal Hgb level was 11.4 +/- 0.9 g/dL (114 +/- 9 g/L) in contrast to 12.4 +/- 1.7 g/dL (124 +/- 17 g/L) in the combination group, which remained significantly different even after adjustment for biologically important covariates (P = 0.01, analysis of covariance). Of the 240 doses of SFGC administered for which infusion records were available, 237 doses were well tolerated; three hypotensive episodes occurred in 2 patients, which did not result in discontinuation of the drug in either case.. Correction of anemia with parenteral iron alone suggests a high prevalence of iron deficiency in patients with CKD. Treatment of concomitant iron deficiency with SFGC was well tolerated in patients with CKD and appears to optimize management of anemia.

Topics: Administration, Oral; Aged; Anemia, Iron-Deficiency; Clinical Pharmacy Information Systems; Databases as Topic; Drug Administration Schedule; Erythropoietin; Female; Ferric Compounds; Glomerular Filtration Rate; Humans; Hypotension; Iron; Kidney Failure, Chronic; Male; Medical Records; Recombinant Proteins; Retrospective Studies; Sucrose; Treatment Outcome; Veterans

The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients.. Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group.. Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012).. The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Time Factors; Transferrin

New patients starting dialysis typically have hemoglobin (Hb) and hematocrit (Hct) levels well below the target range of 11 to 12 g/dL (33% to 36%) recommended by the NKF-K/DOQI. Despite the emphasis on anemia as a quality indicator, low Hb levels often persist for months after dialysis is initiated. Several factors can help promote timely correction of anemia. (a) proactively assessing anemia-related laboratory indicators, (b) calculating weight-based Epoetin alfa starting doses, (c) starting Epoetin alfa therapy on the first day of dialysis for all eligible patients, and (d) proactively assessing patients for conditions that may affect the erythropoietic response. Through proactive, protocol-mandated interventions, nurses can help ensure that anemia is corrected promptly.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nursing Assessment; Recombinant Proteins; Renal Dialysis

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.

Topics: Adult; Age Factors; Anemia; Anemia, Hemolytic; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Humans; Japan; Male; Middle Aged; Myelodysplastic Syndromes; Reagent Kits, Diagnostic; Receptors, Transferrin; Recombinant Proteins; Renal Insufficiency; Sex Factors; Solubility

Patients with the acute porphyrias may develop renal failure and autonomic dysfunction. Renal damage and sympathetic failure may both cause erythropoietin (EPO) deficiency. In this study, we have investigated serum erythropoietin levels and autonomic function in patients with acute porphyria in clinical remission.. Serum erythropoietin levels and the corresponding haemoglobin (Hb) were assayed in 31 patients with acute porphyria and were compared to 15 type 1 diabetic patients with autonomic neuropathy, 23 patients with iron-deficiency anaemia and 18 healthy individuals.. 9 out of 31 porphyric patients showed a normochromic normocytic anaemia with normal ferritin levels. Three patients had borderline-raised serum creatinine levels, and one of them was anaemic. Autonomic function was investigated in seven patients, six of them being anaemic, and the results were normal. Patients with iron-deficiency anaemia showed the expected increase in serum erythropoietin levels in response to a decreasing haemoglobin (r=-0.86, p<0.001). Patients with porphyria had inappropriately low serum erythropoietin levels for the degree of anaemia compared to iron-deficiency patients (p<0.001) although there was still a significant increase in serum erythropoietin with decreasing haemoglobin levels (r=-0.46, p=0.01). In contrast, diabetic autonomic neuropathy patients demonstrated a significant decrease in serum erythropoietin with decreasing Hb levels (r=+0.53, p=0.05).. Patients with acute porphyria may have inappropriately low levels of EPO. In contrast to the diabetic patients, this does not appear to be due to autonomic neuropathy but it may reflect mild renal tubular impairment.

Topics: Adult; Anemia, Iron-Deficiency; Creatinine; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Erythropoietin; Female; Humans; Kidney; Male; Middle Aged; Porphyria, Acute Intermittent; Reference Values

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Bacteremia; Chronic Disease; Drug Hypersensitivity; Erythropoietin; Ferritins; Humans; Injections, Intravenous; Iron; Kidney Diseases; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis

Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-alpha (TNF-alpha), neopterin, CD4(+) lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 microg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log(10) plasma erythropoietin = 2.86 - 0.016.hemoglobin, and log(10) plasma erythropoietin = 4.11 - 0.028.hemoglobin, respectively, with a difference in the slope of the regression lines between log(10) erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.

Topics: Anemia, Iron-Deficiency; CD4 Lymphocyte Count; Erythropoietin; Female; Ferritins; Hemoglobins; HIV Infections; HIV Seronegativity; HIV Seropositivity; Humans; Infant; Iron; Male; Nutritional Status; Tumor Necrosis Factor-alpha; Uganda

The management of anemia in adult end-stage renal disease (ESRD) patients receiving hemodialysis in dialysis facilities is examined. Clinical information was collected for a random sample of adult (age > or = 18 years) patients who received hemodialysis for ESRD between October and December 1999 and included hemoglobin concentrations, epoetin alfa doses and routes of administration, iron prescribing patterns, transferrin saturation levels, and serum ferritin concentrations. Patients whose data did not include hemoglobin concentrations with the weekly epoetin dose were excluded from the analysis. Associations by patient characteristics and geographic region were examined for clinical intermediate outcomes and epoetin alfa and iron prescribing practice patterns. Data were submitted for 8154 patients, and hemoglobin values linked to weekly epoetin alfa doses were available for 7573 of those patients. The mean hemoglobin concentration for patients in the sample was 11.4 +/- 1.3 g/dL. Sixty-seven percent of patients had mean hemoglobin values > or = 11 g/dL. Females, blacks, patients 18-44 years old, and patients receiving hemodialysis for less than six months exhibited significantly lower mean hemoglobin values despite being prescribed, on average, significantly higher epoetin alfa doses than males, whites, older patients, and patients receiving hemodialysis for six months or more (p < 0.001). There was significant regional variation in the prescribing patterns for s.c. epoetin alfa and i.v. iron (p < 0.001). Multivariable logistic regression analysis found significant associations between mean hemoglobin values > 11 g/dL and certain patient characteristics, including white race, hemodialysis for six months or longer, lower prescribed weekly epoetin alfa doses, prescription of i.v. iron, mean transferrin saturation levels > or = 20%, mean Kt/V > or = 1.2, and higher mean serum albumin values. Prescribing patterns for i.v. iron did not vary by the status of patients' iron stores. Regional and patient-specific variations in parameters of anemia management provide pharmacists with the opportunity to contribute to a multidisciplinary team approach to improve the care of hemodialysis patients.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Risk Factors; Transferrin; Treatment Outcome

The European best practice guideline [Nephrol Dial Transplant 1999; 14 (Suppl 5)] (5A) for the management of anaemia suggests that > 85% of the CAPD population should have a haemoglobin level of > 11.0 g/dl.. We developed and implemented an outpatient-based protocol for intravenous iron sucrose (IV Fe) and erythropoietin (Epo) in CAPD patients showing iron deficiency despite oral iron therapy. We managed a total of 103 patients over 13 months of study. All CAPD patients were included, regardless of co-morbidity. Treatment developed in two phases: in phase 1 (reactive) (months 1-8), patients with markers of iron deficiency (ferritin < 100 ng/ml or ferritin 100-500 and percentage hypochromic red cells (%HRC) > or =5) were converted from oral iron to IV Fe (300 mg) and reviewed after 4-8 weeks according to haemoglobin (Hb). In phase 2 (proactive) (months 9-13), the criteria for iron therapy were extended: ferritin < 150 ng/ml or ferritin 150-500 and %HRC > or = 2. Patients then received IV Fe (200 mg) and were reviewed after 4 weeks according to Hb.. The median haemoglobin increased from 11.0 (Inter quartile range, IQR, 10.1-12.6) g/dl to 11.7 (11.0-12.7) g/dl (P = 0.06). The proportion of patients with absolute iron deficiency (ferritin < 100 ng/ml) decreased from 24 to 2%. The percentage of hypochromic red cells (%HRC) decreased from 4 (2-7) to 1 (1-4) (P < 0.01).. An integrated Epo and IV Fe policy increased the number of patients reaching the European guideline from 50 to 75% with no increase in the population median Epo requirements (42 (IQR, 25-95) IU/kg/week vs 45 (27-101) (P = NS)). This study demonstrates the benefit of early (proactive) intervention in achieving population compliance within current guidelines for renal anaemia.

Topics: Anemia, Hypochromic; Anemia, Iron-Deficiency; Clinical Protocols; Erythropoietin; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Iron; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Time Factors

Anemia in persistent nephrotic syndrome (NS) has been described in a few case reports but has not been studied systematically. We present a group of 19 children with NS who developed anemia before the deterioration of kidney function. The aim of our study is to determine whether erythropoietin (EPO) and/or iron deficiency are causative factors and to evaluate the effect of EPO replacement therapy. Serum EPO levels, iron status, and vitamin B(12) concentrations were measured in nephrotic patients with anemia (NS-A) and compared with those of nephrotic children with normal hemoglobin (Hb) levels (NS-NHb; n = 13). Two control groups consisted of age-matched patients without kidney disease or hypoxemia with either iron deficiency anemia (IDA; n = 19) or normal Hb concentrations (NHb; n = 16). Most NS-A patients experienced persistent steroid-resistant NS, whereas most NS-NHb children had steroid-responsive NS. Although serum iron, ferritin, and B(12) levels were significantly lower in NS-A children, appropriate replacement therapy that resulted in normalization of ferritin and/or cobalamin levels did not lead to correction of the anemia. NS-A patients had greater EPO levels than those without anemia (21.6 +/- 3.3 versus 5.5 +/- 0.8 IU/L; P: < 0.001), but their response to anemia was inappropriately low compared with IDA children (EPO, 94.6 +/- 15.1 IU/L) despite similar Hb concentrations. EPO therapy for 4 to 9 months in 6 NS-A children with Hb levels less than 9 g/dL led to resolution of the anemia. In conclusion, anemia is a common feature of persistent NS that develops before the deterioration of kidney function. Depletion of iron stores may contribute to the development of anemia, but iron replacement therapy is ineffective. Nephrotic patients have EPO deficiency with a blunted response to anemia. The EPO deficiency is amenable to EPO therapy, which is recommended for this group of patients.

Topics: Adolescent; Anemia; Anemia, Iron-Deficiency; Child; Child, Preschool; Comorbidity; Erythropoietin; Female; Humans; Male; Nephrotic Syndrome

Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail.. Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis.. With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset.. Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Hospitalization; Humans; Injections, Intravenous; Iron; Middle Aged; Recombinant Proteins; Renal Dialysis

The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEPO) combined with parenteral iron, in the treatment of moderate and severe iron deficiency anemia during pregnancy. Twenty-six pregnant women, who had been ineffectively treated with iron supplementation alone for at least 8 weeks, were enrolled. They met the following criteria for inclusion in the study: hemoglobin (Hb) concentration <8.5 g/dl, evidence of iron deficiency anemia, and absence of other pregnancy complications, or severe systemic diseases. The treatment protocol comprised of a combination therapy with 150 IU/kg rHuEPO subcutaneously three times per week and 100 mg parenteral iron daily, for a total period of 4 weeks. Nineteen out of 26 women (73%) showed a quick response, with Hb reaching normal levels within the first 2 weeks of treatment. They displayed an average of 3.17 g/dl increase in Hb concentration during the total period of therapy, with 3.0 g/dl increase within the first 2 weeks. In 5 women (19.2%) there was no significant increase in Hb levels, while in 2 women (7.6%) a further decline in Hb concentration was observed, that necessitated a blood transfusion. In conclusion, rHuEPO combined with parenteral iron is an effective treatment for moderate and severe iron deficiency anemia during pregnancy, with minimal adverse or side effects. It may serve as an alternative to blood transfusion, or in cases of resistant anemia that are not effectively treated by iron supplementation alone. However, further studies are needed to investigate the poor response observed in about 25% of treated patients.

Topics: Adult; Anemia, Iron-Deficiency; Blood Transfusion; Erythrocyte Indices; Erythropoietin; Female; Gestational Age; Hematocrit; Hemoglobins; Humans; Iron; Pregnancy; Pregnancy Complications, Hematologic; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

To identify the factors determining a high recombinant human erythropoietin (rHuEPO) dose requirement and associated side effects in children undergoing hemodialysis.. We retrospectively analyzed the clinical data of 23 children (aged 5-20 years) undergoing long-term hemodialysis. All subjects received intravenous rHuEPO to maintain hemoglobin levels > or = 10 g/dL and had iron supplement. Subjects were divided into 2 groups: those receiving high-dose rHuEPO (> or = 450 U/kg/wk) and those receiving an average dose (< 450 U/kg/wk). We compared the specific variables between both groups by using Mann-Whitney, Fisher exact, and linear regression tests; a P value < .05 was considered significant.. Four of 23 subjects (17%) received high-dose rHuEPO despite iron repletion. These subjects were small and young and had frequent bacterial infections, high ferritin levels, and severe hyperparathyroidism. Two patients with human immunodeficiency virus infection required high-dose rHuEPO. The main adverse effect of high-dose rHuEPO was an increase in the heparin requirement during hemodialysis.. Age, body weight, inflammatory status, and severity of hyperparathyroidism should be taken into account when adjusting rHuEPO dose for children undergoing hemodialysis. Furthermore, we suggest that high rHuEPO doses are related to an increase in the heparin requirement in these children.

Topics: Age Factors; Anemia, Iron-Deficiency; Body Weight; Child; Erythropoietin; Female; Ferritins; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Kidney Failure, Chronic; Linear Models; Male; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Cytokines; Erythropoietin; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Quality of Life; Vitamin B 12 Deficiency

Serum erythropoietin (Epo) and soluble transferrin receptor (sTR) were measured in a locally defined reference population (n=100): healthy volunteers (n=50); iron- deficiency anaemia (n=41) and haemolytic anaemia (n=9) (beta-thalassaemia, n = 4; autoimmune, n=5). Our data demonstrated an inverse relationship between erythroid activity and Epo levels. The regression line between Ln Epo and haemoglobin (Hb) was highly significant: P < 0.0001, r2=0.8275, Ln Epo=8.5346-0.04275 Hb, confidence limit 95%. The mean observed/predicted (O/P) ratio of Ln (Epo) was 1.01 +/- 0.11. We demonstrated that the serum Epo concentration in this particular population correlated consistently with clinical measures of erythropoietic activity. sTR, a new index of erythropoiesis, varied from 16.1 to 148 nmol/l, mean 62.0 nmol/l in the anaemic patients' group. The relationship between Ln Epo and Ln sTR was highly significant: P < 0.0001. We conclude that locally defined regression analyses are crucial for correct data interpretation and can indicate whether or not Epo production is appropriate or inappropriate. Serial determinations of sTR could help in the assessment of response to therapeutic doses of Epo.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Hemolytic; Anemia, Iron-Deficiency; beta-Thalassemia; Erythropoietin; Female; Hemoglobins; Humans; Linear Models; Male; Middle Aged; Predictive Value of Tests; Receptors, Transferrin; Solubility

The regulation of transferrin receptor (RTF) is related to intracellular iron stores and with the soluble receptor is present in plasma. It has already been demonstrated that in iron deficiency anemia (IDA), receptor expression increases when iron stores decrease. In anemia of chronic diseases (ACD) it is difficult to establish the real iron status because of the influence exerted by inflammatory or infectious diseases on iron metabolism. We studied 30 healthy normal subjects and 42 anemic patients (hemoglobin less than 120 g/L) affected with ACD divided into two groups with and without iron deficiency, in order to establish the diagnostic value of measuring the soluble transferrin receptor (sRTF). We correlated erythropoietin (EPO) (as an erythropoietic stimulating factor) with the decreased hemoglobin values observed in both groups. The results were analysed with an ANOVA statistic test of one way analysis of variance, and there were no significant differences in sRTF values between the ACD groups with or without iron deficiency. The ratio log EPO vs hemoglobin showed a remarkably significant inverse correlation in both groups. We can conclude that sRTF levels are within the normal reference values in these patients and are not related to organic iron. Consequently, sRTF cannot be considered a good parameter for making a diagnosis of iron deficiency in chronic diseases.

Topics: Adult; Aged; Analysis of Variance; Anemia; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Male; Middle Aged; Receptors, Transferrin

Most patients receiving anemia therapy respond well, with a significant rise in hemoglobin concentration. However, approximately 5%-10% of patients fail to show a satisfactory response despite high doses of erythropoietin. The definition of hyporesponsiveness to anemia therapy is somewhat arbitrary, but it is generally regarded as a failure to achieve a hemoglobin concentration of 10-11 g/dL despite a dose of erythropoietin in excess of 200 U/kg weekly. The condition has many causes, the most important ones being iron deficiency, infection or inflammation, and underdialysis. Investigating a patient's poor response to erythropoietin should begin with a check for compliance, followed by screening for iron deficiency. If doubt exists about the presence of iron deficiency, then a trial of intravenous iron may be given. A reticulocyte count may be helpful. A significantly elevated count suggests the presence of blood loss or hemolysis. The level of C-reactive protein (CRP) may be useful as an indicator of underlying inflammation, and underdialysis may be corrected by increasing the dialysis prescription. If other, minor causes of hyporesponsiveness to erythropoietin have been excluded, then a bone marrow biopsy should be performed. Some patients may require higher doses of erythropoietin, and it is not unreasonable to increase the dose to 10,000 U thrice weekly. Some causes of hyporesponsiveness to erythropoietin, such as iron deficiency and underdialysis, are easily corrected; but others, such as primary bone marrow disorders and hemoglobinopathies, are not possible to overcome.

Topics: Anemia; Anemia, Iron-Deficiency; Bacterial Infections; C-Reactive Protein; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Patient Compliance; Peritoneal Dialysis; Recombinant Proteins; Reticulocyte Count; Treatment Failure

Preterm infants are prone to iron deficiency. Their total body iron content at birth is low and gets further depleted by clinical practices such as uncompensated phlebotomy losses and exogenous erythropoietin administration during the neonatal period. Early iron deficiency appears to adversely affect cognitive development in human infants. To maintain iron sufficiency and meet the iron demands of catch-up postnatal growth, iron supplementation is prudent in preterm infants. A dose of 2-4 mg/kg/day is recommended for preterm infants who are fed exclusively human milk. A dose of 6 mg/kg/day or more is needed with the use of exogenous erythropoietin or to correct preexisting iron deficiency. However, due to the poor antioxidant capabilities of preterm infants and the potential role of iron in several oxidant-related perinatal disorders, indiscriminate iron supplementation should be avoided.

Topics: Anemia, Iron-Deficiency; Breast Feeding; Dietary Supplements; Erythropoietin; Ferritins; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Iron Overload; Iron, Dietary; Milk, Human; Nutrition Assessment; Nutritional Requirements; Recombinant Proteins

Nephrology nurses who manage the anemia of end-stage renal disease (ESRD) are often responsible for monitoring, assessing, and intervening to maintain hemoglobin (Hb) and hematocrit (Hct) levels within their facility target range. Consistency in anemia-related outcomes is sometimes compromised when patients exhibit hyporesponse to Epoetin alfa therapy-defined as a temporary or chronic Hb/Hct level below the target range. Early detection of hyporesponse and correction of conditions that are affecting erythrocyte development can sometimes be delayed if clinicians are unable to promptly identify a causative etiology. This article reviews a hyporesponse algorithm worksheet that nurses can use to identify the cause(s) of hyporesponse and guide clinical decision making.

Topics: Aged; Algorithms; Anemia, Iron-Deficiency; Decision Trees; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nurse's Role; Nursing Assessment; Recombinant Proteins; Renal Dialysis; Risk Factors; Treatment Failure

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Iron; Iron Overload; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia.. 132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed.. The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively.. Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.

Topics: Adult; Anemia; Anemia, Hemolytic, Autoimmune; Anemia, Iron-Deficiency; Autoantibodies; Erythropoietin; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prospective Studies

Anemia is a frequent complication of cancer and its treatment. A defect in erythropoietin production has been advocated as being the main cause of anemia in cancer patients. We studied serum erythropoietin levels in 74 patients with solid tumors and in a control group consisting of 20 otherwise healthy individuals without any malignancy, who have only iron deficiency anemia. Serum erythropoietin levels were measured by enzyme immunoassay in cancer patients without anemia (n=34), and in anemic cancer patients (n=40); either receiving chemotherapy (n=21) or not (n=19). Anemic cancer patients were found to have decreased response of erythropoietin for a given hemoglobin level (mean, 40.1+/-34.7 u/ml), compared with the patients having only iron deficiency anemia (mean, 69.7+/-68.6 u/ml) (P<0.05). In patients with iron deficiency anemia having no malignancy, erythropoietin response was remarkably high and inversely correlated with the level of hemoglobin (r=-0.69; P=0. 05). Although there was no correlation between hemoglobin and erythropoietin response in cancer anemia (r=-0.07), serum levels of erythropoietin were found to be higher in anemic cancer patients (mean, 40.1+/-34.7 u/ml), compared with cancer patients with normal hemoglobin values (mean, 19.96+/-18.4 u/ml). There was not any statistically significant difference between erythropoietin levels in anemic cancer patients with or without chemotherapy (mean, 43. 7+/-37.7 u/ml and 41.9+/-30.08 u/ml respectively; P>0.05). No difference in serum erythropoietin levels were noted in patients treated with cisplatin or non-cisplatin containing regimens (mean, 48.36+/-33.12 u/ml and 38.55+/-43.52 u/ml, respectively; P>0.05). In this study, we demonstrated that anemia in cancer patients was caused by blunted erythropoietin response, rather than its quantitative deficiency. Serial measurements, however, should be considered in patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms

A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these observations.

Topics: Anemia; Anemia, Iron-Deficiency; Animals; Base Sequence; Carcinoma, Hepatocellular; Ceruloplasmin; Cloning, Molecular; Consensus Sequence; DNA-Binding Proteins; Enhancer Elements, Genetic; Erythropoietin; Female; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Mice; Molecular Sequence Data; Nuclear Proteins; Pregnancy; Promoter Regions, Genetic; Recombinant Proteins; Sequence Alignment; Transcription Factors; Transcriptional Activation; Transfection; Tumor Cells, Cultured

This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization.. The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown.. In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period.. The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment.. Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Topics: Aged; Anemia, Iron-Deficiency; Erythropoietin; Female; Glomerular Filtration Rate; Heart Failure; Hospitalization; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Male; Prevalence; Retrospective Studies; Severity of Illness Index; Stroke Volume

An increasing number of dialysis facilities are empowering nurses to coordinate, monitor, and manage most aspects of anemia-related care. Careful analysis of the trends in laboratory values can provide nurses with a valuable assessment tool to guide therapeutic decisions. This article reviews several proven methods for analyzing laboratory trends and uses case studies to illustrate how to interpret these trends to identify potential etiologies that can cause hyporesponse to Epoetin alfa therapy.

Topics: Aged; Anemia, Iron-Deficiency; Drug Monitoring; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Nursing Assessment; Renal Dialysis

Anemia is an important cause of morbidity, and may be associated with increased mortality in patients with end-stage renal disease (ESRD) receiving dialysis. Therapy with recombinant human erythropoietin (rHuEPO) has revolutionized the care of ESRD patients, but this is a costly medication and concerns have been expressed about whether the outcome, as measured by achieved hematocrit (Hct), could be improved. The number and proportion of ESRD patients receiving rHuEPO increased steadily from 1995 to 1998, as did the dose of rHuEPO per patient. The amount of intravenous iron administered to patients increased markedly over the study period. The patients' mean hematocrit also rose, but proportionally less over the study period. The increase in both the amounts of payments per patient for rHuEPO, and the number of patients receiving rHuEPO over this time has resulted in a marked increase in the total costs to Medicare for this therapy. We suggest that a combination of payment regulations, provider financial opportunities and disincentives, and patient resistance to the effects of rHuEPO, as a result of both iron deficiency and inflammation, largely explain the findings.

Topics: Anemia, Iron-Deficiency; Cost-Benefit Analysis; Drug Utilization; Erythropoietin; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Prognosis; Recombinant Proteins; Registries; Renal Dialysis; Treatment Outcome; United States

A large, 4-year, retrospective study of the HCFA end-stage renal disease (ESRD) claims database, Parts A and B, was conducted to determine the association between hematocrit (Hct) level and survival in patients on hemodialysis. Patients who survived the last 6 months of each year and had at least 4 Epoetin alfa claims qualified for the study. Cohort entry years were 1990 through 1993, with the relative risk (RR) of mortality evaluated during the following year. Patients were stratified into four groups on the basis of mean Hct levels in the 6-month entry period: < 27%, 27% to < 30%, 30% to < 33%, and 33% to 36%. Using the 30% to < 33% Hct group as reference (relative risk (RR) = 1), patients whose mean 6-month Hct was in the 33% to 36% range were associated with significantly lower RR of mortality, while patients whose mean 6-month Hct was below 30% were associated with significantly higher RR of mortality. This epidemiologic study highlighted an important association between higher hematocrits in hemodialysis patients and lower RR of mortal.

Topics: Anemia, Iron-Deficiency; Centers for Medicare and Medicaid Services, U.S.; Cohort Studies; Comorbidity; Epidemiologic Studies; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Hospitalization; Humans; Insurance Claim Reporting; Kidney Failure, Chronic; Medicare; Nurse's Role; Proportional Hazards Models; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Survival Analysis; Survival Rate; United States

Topics: Abdominal Pain; Adult; Analgesics, Non-Narcotic; Anemia, Iron-Deficiency; Appendicitis; Epoetin Alfa; Erythropoietin; Fever; Gastrointestinal Hemorrhage; Glomerulonephritis; Hematinics; Humans; Hypertension; Ibuprofen; Kidney Failure, Chronic; Male; Nursing Diagnosis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recombinant Proteins; Renal Dialysis

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Ferric Compounds; Hematinics; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Topics: Anemia, Iron-Deficiency; Child; Epidermolysis Bullosa Dystrophica; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Male; Recombinant Proteins; Sucrose

The relationship between serum erythropoietin (EP) and hemoglobin (Hb) concentrations was investigated in patients of iron deficiency anemia (IDA) in the course of iron replacement therapy to elucidate how the therapy induced changes in that relationship. At first Hb-dependent EP levels were determined in 123 IDA patients prior to the treatment by the third-degree logarithmic regression of EP on the Hb deficit (d-Hb). Following the start of iron supply, the deviation of observed EP values from the predicted level (EPc), i.e., delta-EP, was most obvious at the next phase of the onset of reticulocyte crisis; however, this deviation reduced with the alleviation of IDA. The value in maximum phase (delta-EPmx), as individually defined for each of 95 patients, correlated significantly with the severity of the pretreatment ID state (r = 0.502, p < 0.01). Partial correlation analysis revealed that about 80% of this gap was attributable to the ID state. Also, it was assumed that EP upregulation was twice that attributable to the Hb-deficit factor alone. The phase sequence of the delta-EP versus d-Hb relationship in 21 relapsed patients demonstrated a different rout from that observed in their improvement phase. The ID state-induced upregulation of EP, i.e., EPc, was followed by a therapy-induced overshooting drop that was attributable to acute uptake of EP by shifted erythroid precursors. From the viewpoint of erythropoietic regulation, the subsequent down-regulation of EP in the mid to late phases was considered appropriate for the prevention of Hb over production.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Hemoglobins; Humans; Iron; Male; Middle Aged

Data for iron-status indices in continuous ambulatory peritoneal dialysis patients are limited. The reliability of commonly used indices for the diagnosis of iron-deficiency anemia in peritoneal dialysis patients is still unknown. To study diagnostic values of iron-status indices, including serum ferritin, transferrin saturation, reticulocyte hemoglobin content, and bone marrow-stainable iron, 21 stable anemic peritoneal dialysis patients who have been treated with erythropoietin and oral iron supplementation for more than 3 months were enrolled in this study. The mean age was 51.4 +/- 2.9 years; dialysis duration, 28.7 +/- 5.1 months; initial hemoglobin, 8.4 +/- 0.2 g/dL; erythropoietin dosage, 71 +/- 2 micro/kg/wk; serum albumin, 3.5 +/- 0.1 g/dL; intact parathyroid hormone (PTH), 233 +/- 44 ng/mL; serum ferritin, 643 +/- 135 ng/mL; transferrin saturation, 33.93% +/- 3.9%; and reticulocyte hemoglobin content, 31.6 +/- 4 pg. Bone marrow aspiration was performed in all patients to determine marrow iron content and exclude hematological disorders. All patients were treated with 1, 000 mg of intravenous ferric saccharate infusion in two divided doses more than 1 week apart. Patients who responded to the iron infusion within 3 months by increasing serum hemoglobin of greater than 1 gm/dL more than baseline were defined as being functional iron deficient before the intravenous iron infusion. Serum ferritin, transferrin saturation, and reticulocyte hemoglobin content were followed serially after iron infusion. Fifteen patients (71.4%) responded to the iron administration, indicating iron deficiency. Nine of 13 (69%) patients with the presence of bone marrow-stainable iron still responded to intravenous iron supplementation, suggesting functional iron deficiency. Absence of bone marrow-stainable iron was not a sensitive marker for the diagnosis of iron deficiency, 25% sensitivity. No single value of iron-status indices that can definitely exclude iron-deficiency anemia in peritoneal dialysis patients was found. Therefore, failure to increase hemoglobin concentration after intravenous iron administration should be shown before excluding iron-deficiency anemia as a cause of poor erythropoietic response to erythropoietin therapy.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Predictive Value of Tests; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferritins; Hematinics; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis

The Health Care Financing Administration (HCFA) End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations (TSATs) and iron prescription practices have improved over the last 5 years, we sought to determine whether there are continued opportunities for improvement of this domain of care. A random sample of 7,292 adult in-center hemodialysis patients was selected for the period October through December 1996. Hematocrit values, TSATs, serum ferritin concentrations, epoetin-alfa dosing, and iron prescriptions were abstracted from 4,991 patient medical records to assess anemia management practices. The mean hematocrit for this cohort was 32.6% +/- 3.5%, and 72% of patients had hematocrit values greater than 30%. Ninety-four percent of patients received epoetin alfa intravenously, with a mean weekly epoetin dose of 202.4 +/- 137.2 U/kg. The mean TSAT was 27.4% +/- 12.6%; 73% of patients had TSATs >/= 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79% and 12% of patients had serum ferritin concentrations greater than 100 ng/mL and greater than 800 ng/mL, respectively. Nine percent of the sample had TSATs less than 20% and serum ferritin concentrations less than 100 ng/mL. Regardless of the TSAT, approximately three fourths of patients received iron; only about half received IV iron. Of the subset of patients with TSATs less than 20% and serum ferritin concentration less than 800 ng/mL, only 53% were prescribed IV iron. Although substantial improvements have been made in anemia management in hemodialysis patients over the last 5 years, significant opportunities persist to improve iron prescription practices.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hematocrit; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Quality Indicators, Health Care; Recombinant Proteins; Renal Dialysis; Transferrin; United States

Assessment of iron status is important, because iron deficiency and overload have pathologic consequences. Serum ferritin, the function of which is unknown, is frequently used to assess labile iron stores for the purpose of ensuring their adequacy for erythropoiesis. However, measurable ferritin levels can be increased when tissue ferritin is released during cellular injury, and erythropoietic blockade can increase the labile iron pool, elevating serum ferritin levels despite suppressed erythropoiesis. Erythropoietin-stimulated red blood cell (RBC) production can quickly decrease the labile cellular iron pool and reduce serum ferritin, unless supplemental iron is supplied. A serum ferritin level less than 12 microg/L indicates that there is no iron in the stores (absolute iron deficiency), and levels above 15 microg/L may still not be sufficient to meet erythropoietic demand. This is particularly true in patients receiving erythropoietin, in which the stimulated erythropoiesis requires extra iron supplies. Because of the limitations of serum ferritin measurements and questions regarding the effects of free iron, clinicians need not be too alarmed by high serum ferritin levels. At the very least, safety concerns must be balanced against the real need for iron supplementation to maintain adequate erythropoiesis.

Topics: Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Ferritins; Humans; Iron; Iron Deficiencies; Iron Overload; Renal Dialysis

Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability.. To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures.. While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements.. Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.

Topics: Adolescent; Anemia, Iron-Deficiency; Child; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis

Despite the progress in the knowledge of iron metabolism, its precise assessment remains uneasy. Serum ferritin assesses the extent of storage iron. Serum iron and the percentage of transferrin saturation evaluate the tissues' iron supply. But these parameters are indirect measurements and they do not reflect marrow iron supply. Serum transferrin receptors, red cell ferritin and red cell zinc protoporphyrin are good indicators of this iron supply to the erythroid marrow for erythropoiesis. Since the introduction of recombinant human erythropoietin, it has become apparent that an adequate iron supply to the bone marrow is essential for a satisfactory hematopoietic response. In some cases, despite a high baseline ferritin, iron may not be sufficiently released from reserves in the bone marrow, resulting in a functional iron deficiency. The percentage of hypochromic red cells and reticulocyte haemoglobin content tends to reflect direct marrow iron status.

Topics: Anemia, Iron-Deficiency; Bone Marrow; Erythropoietin; Ferritins; Hematopoiesis; Humans; Iron

We assessed zinc protoporphyrin (ZPP) and the percentage of hypochromic erythrocytes in patients with advanced acquired immunodeficiency syndrome (AIDS) treated with recombinant erythropoietin (rhEPO).. Patients received 150 IU rhEPO subcutaneously every second day for 10 days, and 150 IU rhEPO plus 62.5 mg of intravenous iron every second day for an additional 10 days.. Before rhEPO therapy, ZPP was at 64.3 +/- 27.3 micromol/mol heme and the percentage of hypochromic erythrocytes was elevated at 9.7%, indicating mild functional iron deficiency. Ferritin was 1,002 +/- 956 microg/L, with transferrin saturation of 19.1 +/- 9.7%. Under rhEPO alone, ZPP rose to 80.1 +/- 21.6 micromol/mol heme and the percentage of hypochromic red cells rose to 22.9 +/- 4.7%; ferritin fell to 705 +/- 601 microg/L and transferrin saturation fell to 12 +/- 6.3%. When rhEPO was supplemented with iron, ZPP fell to 70.4 +/- 20.5 micromol/mol heme, the percentage of hypochromic red cells fell to 14.7 +/- 3.4%; ferritin was unchanged at 771 +/- 62 microg/L and transferrin saturation rose to 20.5 +/- 5.5%.. In contrast to ferritin and transferrin saturation, ZPP and the percentage of hypochromic erythrocytes effectively detect the functional iron deficiency under rhEPO therapy in advanced AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Humans; Iron; Male; Metalloporphyrins; Middle Aged; Protoporphyrins; Recombinant Proteins; Severity of Illness Index

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.

Topics: Aged; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Male; Middle Aged; Renal Dialysis; Transferrin

To evaluate storage iron deficiency and iron-deficient erythropoiesis we determined, in a cross-sectional study of 95 patients mainly including end-stage renal disease patients (ESRD) with (32) and without rh-EPO therapy (55), the following parameters: hemoglobin, mean corpuscular red cell volume, ferritin, transferrin saturation (TS), zinc protoporphyrin (ZPP) and soluble transferrin receptor (TfR). In the dialysis group the percentage of positive samples with each marker of tissue iron supply defined as TS < 20%, ZPP > 40 mumol/mol Heme and TfR > 3.05 microgram/ml was as follows: TS 43.7% and 32.2% at a diagnostic threshold level of < 16%, ZPP 33.3% and TfR 17.2%. Manifest storage iron deficiency defined as ferritin < 30 ng/ml was observed in 5.7% of the samples while the mean ferritin concentration of the rh-Epo treated dialysis patients was 509.3 ng/ml compared to 262.5 ng/ml in the group without rh-EPO therapy. These data reflect a generous iron substitution in our series taking a TS < 20% as an intervention criterion. Looking at the different results of the three markers the best correspondence was found between ZPP and TfR resulting in a weak positive correlation (+0.64). In conclusion, we found quite different results with different assays when evaluating endogenous iron availability in our series of mainly ESRD patients in a cross-sectional study. Because a gold-standard is not defined further firm conclusions cannot be drawn from this type of study. The adequacy of the different parameters of iron metabolism including threshold levels and, consequently, the decision and route of iron substitution deserve an evaluation in a longitudinal study to characterize the best marker or marker combination in this setting.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Protoporphyrins; Receptors, Transferrin; Recombinant Proteins; Transferrin

Recombinant human erythropoietin (rHuEPO) is an important component of anemia management in patients with chronic renal failure, however, it can lead to functional iron deficiency (FID). Patients with FID are less likely to have an optimal response to rHuEPO (Cavill et al., 1997). Intravenous (i.v.) iron dextran is often required to replace iron losses, maintain adequate iron stores, and correct iron deficiency. The following article provides a rationale for the use of IV iron dextran and details one unit's protocol and experience with its use.

Topics: Anemia, Iron-Deficiency; Drug Monitoring; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Nursing Assessment; Recombinant Proteins

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Topics: Adult; Anemia, Iron-Deficiency; Case-Control Studies; Erythropoietin; Female; Humans; Male; Middle Aged; Receptors, Transferrin; Recombinant Proteins

Current guidelines recommend maintaining the hematocrits of chronic hemodialysis patients in the low to mid-30s. Maintaining patients' hematocrits within a narrow range requires frequent monitoring of their hematocrits and iron studies and periodic adjustment of erythropoietin doses and administration of intravenous iron. We designed a simple anemia treatment algorithm to streamline the management of anemia in hemodialysis patients. The protocol required formal monthly decisions about the administration of intravenous iron or changes in erythropoietin dose. This algorithm was implemented by dialysis nurses and evaluated prospectively for 6 months in a single dialysis unit (30 patients). The proportion of patients whose hematocrits were within the desired target (31% to 35%) increased from 27% at baseline to 61% during months 4 through 6 of the algorithm. Conversely, the proportion of patients whose hematocrit values were below the target decreased from 46% at baseline to 18% during months 4 through 6 of the algorithm (P=0.004). The percentage of patients whose hematocrit values were above the target did not increase. The proportion of patients whose transferrin saturation was less than 18% decreased from 47% at baseline to 20% during months 4 through 6 of the algorithm (P=0.04). The weekly erythropoietin dose administered decreased from 11,200+/-1,400 units at baseline to 9,400+/-1,200 units in month 6 of the algorithm (P=0.06). We conclude that a simple anemia treatment algorithm implemented by dialysis nurses is feasible and efficacious and may increase the proportion of hemodialysis patients whose hematocrit values are within the target range, without increasing erythropoietin requirements.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome

Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss.. Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete rHuEPO-treated PD patients (serum ferritin 100-500 microg/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen).. Mucosal uptake (13.4+/-9.8%), mucosal transfer (0.34+/-0.18) and iron retention (4.9+/-4.0) in PD patients was significantly lower than in controls (42.9+/-18.8%, P < 0.0001, 0.63+/-0.18, P < 0.0001, and 28.0+/-16.7%, P<0.0001).. Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.

Topics: Absorption; Adolescent; Adult; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hemorrhage; Humans; Infusions, Intravenous; Iron; Iron Compounds; Iron Deficiencies; Kidney Diseases; Male; Peritoneal Dialysis; Receptors, Transferrin; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Erythropoietin; Humans; Injections, Intravenous; Iron; Renal Dialysis

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Ferritins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis

In haemodialysis (HD) patients, functional iron deficiency frequently appears due to recombinant human erythropoietin (r-HuEPO) treatment. However, the diagnosis of iron deficiency is not always easy in such patients. Recent studies have shown that the serum transferrin receptor (s-TfR) level is a sensitive, quantitative measure of tissue iron deficiency. In this study, we examined the changes in s-TfR levels in patients with iron deficiency anaemia due to r-HuEPO treatment. We compared s-TfR levels of 24 patients with i.v. administered r-HuEPO (50-70 U/kg/dose) at the end of each dialysis session (three times a week) and diagnosed as having iron deficiency anaemia by routine laboratory methods (ferritin <50 microg/l and transferrin saturation <16%) with s-TfR levels of 32 patients not receiving r-HuEPO and without iron deficiency anaemia. Also, 40 healthy volunteer subjects were included in the study as a control group. Serum ferritin and transferrin receptor levels were measured with ELISAs using monoclonal reagents. There were no differences between the two groups with and without iron deficiency anaemia with respect to mean age, body weight, haemodialysis duration, haemoglobin and serum creatinine levels (p>0.05). For s-TfR levels, while no difference was present between the control and the non-iron deficiency groups (p>0.05), the iron deficiency group had higher s-TfR values than those of both the control and non-iron deficiency groups (p<0.001). Besides, there was an inverse correlation between haemoglobin and s-TfR levels in patients with iron deficiency anaemia (r = -0.85, p<0.0001). We conclude that the measurement of s-TfR levels may be useful in the diagnosis of functional iron deficiency in haemodialysis patients receiving r-HuEPO.

Topics: Adult; Anemia, Iron-Deficiency; Erythropoietin; Female; Humans; Male; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis

Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients.. Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group.. Two University Hospital Intensive Care Departments.. A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = -0.81, p < 0.001), but not in the critically ill patients (r = -0.09, NS), except in a subgroup of non-septic patients without renal failure (r = -0.61, p < 0.01).. EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

Topics: Acute Kidney Injury; Aged; Anemia, Hemolytic; Anemia, Iron-Deficiency; Case-Control Studies; Critical Illness; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematocrit; Humans; Intensive Care Units; Male; Middle Aged; Regression Analysis; Respiratory Distress Syndrome; Sepsis

The treatment efficacy of erythropoietin (EPO) in end-stage renal disease (ESRD) can be limited by deficiencies of iron, folate, or vitamin B12, by hyperparathyroidism, or by aluminum intoxication. Since EPO costs are significant, this study attempted to determine the cost-effectiveness of performing a panel of screening tests for anemia before starting EPO. Anemia screening was performed prospectively in 48 new-onset ESRD patients at the Ralph H. Johnson Veterans Affairs Medical Center before EPO treatment was started. Serum iron, transferrin, folate, vitamin B12, parathyroid hormone, and aluminum levels were determined, and transferrin saturation (Tfsat) was calculated at the first dialysis session. At presentation for dialysis, the mean hematocrit was 0.264 +/- 0.036 and the mean blood urea nitrogen was 32 +/- 2 mmol/L. Eighteen patients (37.5%) had a serum iron level lower than 7 micromol/L, suggesting iron deficiency. Twenty-five patients (52%) had Tfsat less than 0.20, consistent with overt iron deficiency. No patient was found to be vitamin B12 deficient, to be aluminum intoxicated, or to have significant hyperparathyroidism. One patient had folate deficiency. A cost-effectiveness analysis was performed assuming that (1) EPO would be given at an average starting dose of 6,000 U/wk at a cost of $14/2,000 U of EPO; (2) that without screening 1 month would elapse before a poor response was identified; and (3) that the failure to treat aluminum intoxication and hyperparathyroidism or to replete iron, vitamin B12, or folate deficiency would significantly impair the response to EPO. The Tfsat screen had a cost-effectiveness ratio of 0.2019, saving approximately $5.00 in EPO use for each dollar of test administration. All other screens had cost-effectiveness ratios greater than 1.0, indicating that their testing costs exceeded dollar savings in EPO use. In conclusion, iron deficiency is common in anemic patients starting dialysis, but other causes of anemia are not. It is imperative that current clinical practices be influenced by cost-effectiveness considerations. Given the cost of laboratory screens, and the relative ineffectiveness of the other screens examined here to identify factors known to impair the response to EPO, anemia screening before initiating EPO therapy should be limited to tests to identify iron deficiency.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Clinical Laboratory Techniques; Cost-Benefit Analysis; Drug Costs; Erythropoietin; Female; Hospital Costs; Hospitals, Veterans; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Prospective Studies; Recombinant Proteins; Renal Dialysis; Sensitivity and Specificity; South Carolina

Traditional reticulocyte counts provide only a partial estimate of the erythropoietic bone marrow activity and do not account for qualitative variations of reticulocyte cellular indexes and hemoglobin content in particular. We have studied a new integrated parameter, reticulocyte hemoglobin (retHb), that quantifies in grams per liter the hemoglobin contained in the circulating reticulocyte compartment and is obtained by multiplying the absolute reticulocyte count and the reticulocyte cell hemoglobin content. In 50 normal control subjects, retHb values were 1.76 +/- 0.59 g/L. The retHb values were lower in patients double heterozygous for HbS and HbC (SC disease) (3.33 +/- 1.52 g/L, n = 13) compared with homozygous HbS disease (SS) with concomitant alpha-thalassemia (5.27 +/- 1.51 g/L and 5.48 +/- 1.06 g/L for 12 patients with 3 alpha-genes and 3 patients with 2 alpha-genes, respectively) and to SS disease with no alpha-thalassemia (6.47 +/- 3.05, n = 20). The hemoglobin contained in the red blood cell pool (rbcHb) also can be calculated by subtracting retHb from the total hemoglobin. The ratio between the two pools (rbcHb/retHb, normal value 76.6 +/- 21.9, n = 50) provides a rough estimate of red blood cell survival. It was 9.8 +/- 4.1 in SS disease, 16.2 +/- 10.1 and 14.7 +/- 5.0 in SS disease with 3 and 2 normal alpha-genes, respectively, and 36.6 +/- 17.8 in SC disease with no alpha-thalassemia. We also studied retHb in patients receiving hydroxyurea therapy for SS disease, intravenous or oral iron for iron deficiency, or recombinant human erythropoietin (r-HuEPO) therapy. All these conditions are characterized by changes in reticulocyte counts and marked variations in reticulocyte cellular hemoglobin contents, which can be integrated into the retHb parameter. Measurement of retHb and the rbcHb/retHb ratio may provide an estimate of the reduction in red blood cell survival and the severity of hemolysis in various anemias and allow more precise monitoring of the response to hydroxyurea, iron, r-HuEPO, or other therapies.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Anemia, Sickle Cell; Antisickling Agents; Erythropoiesis; Erythropoietin; Hematology; Hemoglobins; Humans; Hydroxyurea; Injections, Intravenous; Iron; Recombinant Proteins; Reference Values; Reticulocyte Count; Reticulocytes

To define the etiology of anemia post-renal transplantation, we assessed hematologic parameters and EPO levels in 38 anemic and 16 non-anemic control renal transplant recipients (RTRs) with varying degrees of allograft function at periods > 3 months post-transplantation. Significant differences between the two groups were found for serum creatinine (Cr) 291.7 +/- 26.5 vs. 203.3 +/- 26.5 mumol/l, p < 0.01; iron 9.3 +/- 0.92 vs. 13.6 +/- 1.7 mumol/l, p < 0.05; and ferritin 345.5 +/- 90.8 vs. 91.1 +/- 18.5 micrograms/l, p < 0.01. Serum EPO levels were inappropriately low in anemic patients with no significant correlation between EPO and Cr or hematocrit (Hct) levels. Serum iron was the only predictive factor for anemia on regression analysis (p < 0.05). Ferritin levels did not correlate with serum iron or Hct, and may be falsely elevated in iron deficient RTRs. Iron deficiency, poor renal function and inappropriately low EPO levels are major contributors to the 12% of our outpatient renal transplant population who are anemic.

Topics: Anemia; Anemia, Iron-Deficiency; Blood Urea Nitrogen; Chronic Disease; Creatinine; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Follow-Up Studies; Forecasting; Graft Rejection; Hematocrit; Humans; Iron; Iron Deficiencies; Kidney Transplantation; Male; Middle Aged; Regression Analysis; Reticulocyte Count; Transplantation, Homologous

Topics: Anemia, Iron-Deficiency; Critical Illness; Cytokines; Erythropoietin; Humans

Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect masked iron deficiency, and optimal methods of iron replacement, remain unanswered. To investigate these issues, studies were performed in anemic chronic hemodialysis patients. A number of standard hematologic measurements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8.5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a greater than 20% increase from baseline in the serum TfR or absolute reticulocyte count, with a sensitivity of 92%. In patients on rHuEPO replacement with serum ferritin levels greater than 30 microg/L, none of the panel of tests, including serum TfR, reliably detected masked iron deficiency. In a long-term study over 5 months in patients on a stable maintenance dose of EPO, a gradual decline in total body iron occurred, even in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is useful for predicting a hemoglobin response when initiating rHuEPO therapy, and combined with automated reticulocyte counting it is valuable for predicting a hemoglobin response when increasing the dose of rHuEPO. The serum TfR loses its specificity for detecting tissue iron deficiency in patients on maintenance rHuEPO therapy because of increased erythropoiesis, which itself raises serum TfR levels.

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Recombinant Proteins; Renal Dialysis; Reticulocyte Count; Sensitivity and Specificity; Time Factors

Erythropoietin levels were determined in 50 Greek females: 20 beta-thalassaemia (beta-thal) heterozygotes, 15 with a diagnosis of iron-deficiency anaemia and 15 normal controls. In beta-thal trait carriers, the erythropoietin levels were slightly higher than in normal controls (16.65 +/- 4.43 vs. 12.84 +/- 2.47 mU/ml); these levels were significantly lower than those in iron-deficient subjects with the same degree of anaemia (55.24 +/- 31.35 mU/ml). In both groups, the erythropoietin levels are statistically correlated with the severity of anaemia (r = -0.537 p < 0.05 for iron deficiency; r = -0.610 p < 0.01 for beta-thal heterozygotes). In beta-thal heterozygotes, a close inverse correlation with red cell number and erythropoietin levels was also noted. It is suggested that microcytosis accompanying beta-thal trait constitutes an additional factor intervening in the regulation of erythropoiesis.

Topics: Adult; Anemia, Iron-Deficiency; beta-Thalassemia; Erythropoietin; Female; Heterozygote; Humans

We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Quality of Life; Renal Dialysis

Early detection of iron sufficiency at the level of the erythropoietic cell is necessary to optimize management of uremic anemia with recombinant human erythropoietin (rHuEPO). "Absolute" and "functional" iron deficiency are the most important factors causing resistance to administered rHuEPO. Transferrin saturation and serum ferritin measurements have been noted to be insensitive and inaccurate measures to detect functional iron deficiency. Recently, the reticulocyte hemoglobin content (CHr) has been shown to be a sensitive and specific indicator of functional iron deficiency in nondialysis patients treated with rHuEPO. The purpose of this study is to compare CHr with currently used indices of iron sufficiency in rHuEPO-treated hemodialysis (HD) patients. In study 1, 364 stable HD patients were studied at two outpatient dialysis centers. CHr was normally distributed, with a mean value of 28.3 pg, and was consistent over two consecutive monthly samples in each center. CHr was weakly but consistently correlated with transferrin saturation and serum ferritin. CHr and reticulocyte number were inversely correlated with red blood cell (RBC) number, suggesting that the erythropoietic stimulus of routinely administered rHuEPO may have resulted in functional iron deficiency. Month-to-month changes in CHr correlated weakly with changes in serum iron and percent transferrin saturation, but not at all with changes in serum ferritin. When we analyzed those patients with baseline CHr less than 26 pg, a level strongly suggestive of functional iron deficiency, these correlations strengthened, and in addition, month-to-month changes in CHr correlated strongly and directly with concomitant changes in RBC count, hemoglobin, and hematocrit, suggesting that rising CHr was indicative of an erythropoietic response. In study 2, 79 patients received a single-dose infusion of 500 mg iron dextran. After intravenous iron, CHr rose within 48 hours, peaked at 96 hours, and then fell toward baseline. Patients who were iron deficient by standard measures (serum ferritin < 100 ng/mL or transferrin saturation less than 20%) had a greater and a sustained CHr response to intravenous iron dextran. A CHr less than 28 pg at baseline predicted functional iron deficiency, defined as a corrected reticulocyte increase of greater than 1% to iron dextran, more accurately than transferrin saturation, ferritin, or their combination. Eighty-two percent of individuals who were iron deficient at baselin

Topics: Anemia, Iron-Deficiency; Biomarkers; Drug Resistance; Erythrocyte Count; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Female; Ferritins; Follow-Up Studies; Forecasting; Hematinics; Hematocrit; Hemoglobins; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Reticulocytes; Sensitivity and Specificity; Transferrin

To demonstrate that intravenous (IV) iron therapy rapidly can secure the physiologic correction of severe nonhemorrhagic anemia more safely than blood component therapy and recombinant erythropoietin treatment.. An 18-year-old woman with beta-thalassemia in her 33rd week of gestation had a hemoglobin level of 4.8 g/dL and an erythropoietin value of 191 mU/mL. After IV iron administration, erythropoietin rapidly decreased and hemoglobin increased to 8.1 g/dL in correlation with estriol elevation. A healthy infant with normal hemoglobin and ferritin levels was delivered at 42 weeks by cesarean.. Intravenous iron administration rapidly corrected severe nonhemorrhagic anemia in a pregnant patient and may produce an improvement in fetal indices. High erythropoietin levels predict a good response to iron and may obviate the need for blood transfusions and recombinant erythropoietin administration, at least until this therapy is tried.

Topics: Adult; Anemia, Iron-Deficiency; beta-Thalassemia; Erythropoietin; Female; Humans; Infusions, Intravenous; Iron; Pregnancy; Pregnancy Complications, Hematologic

A compensated haemolytic state is defined by decreased red cell life-span without anaemia, i.e. by increased erythropoiesis in the absence of the physiological stimulus for erythropoietin (Epo) production. We evaluated s-Epo levels and the expansion of erythropoiesis (as measured by circulating transferrin receptor, s-TfR) in 32 patients with hereditary spherocytosis (HS) with the aim of verifying whether the enhanced erythropoiesis of compensated haemolysis was Epo-dependent. 20 of the patients (62.5%) had normal Hb values (> 12 g/dl in females and > 13 g/dl in males). Their compensated haemolytic state was the result of up to 8.2 times normal s-Epo and up to 3.9 times normal s-TfR levels, which were maintained by physiological regulation of erythropoiesis, as documented by the inverse dependence of Hb on s-Epo levels. Considering that patients with iron-deficiency anaemia represented the predicted physiological Epo response to anaemia, the observed/predicted in s-Epo ratio (O/P ratio) was calculated in HS patients with anaemia and was used as an index of the adequateness of Epo production. All the anaemic HS patients had an O/P ratio > 1, documenting inappropriately high s-Epo levels. This work demonstrates that the compensated haemolytic state of HS patients is produced by an inappropriately high s-Epo level, and that the pattern of Epo overproduction is a biological characteristic of the disease.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Child; Erythropoiesis; Erythropoietin; Female; Hemolysis; Humans; Male; Middle Aged; Receptors, Transferrin; Reference Values; Spherocytosis, Hereditary

Two siblings were identified with severe hypoproliferative microcytic anemia and iron malabsorption, in the absence of any gastrointestinal disorder or blood loss. These children had severe microcytosis (MCV 48 fl, hemoglobin 7.5 g/dl) with decreased serum iron, elevated serum TIBC, and decreased serum ferritin, despite prolonged treatment with oral iron. An iron challenge study with an oral dose of 2 mg/kg elemental iron as ferrous sulfate documented iron malabsorption. After treatment with intravenous iron dextran, there was an absence of the expected reticulocytosis and only a partial correction of the hemoglobin, hematocrit, and microcytosis. The bone marrow was hypocellular with abnormal iron incorporation into erythroid precursor cells. This appears to be a rare form of inherited anemia characterized by iron malabsorption and disordered iron metabolism that only partially corrects after the administration of parenteral iron. These features resemble those found in the microcytic mouse (mk/mk), which also has severe microcytic anemia and iron malabsorption that partially responds to parenteral iron.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Animals; Biological Transport; Bone Marrow; Cell Compartmentation; Cell Size; Child; Child, Preschool; Colony-Forming Units Assay; Craniosynostoses; Drug Resistance; Erythrocytes, Abnormal; Erythroid Precursor Cells; Erythropoietin; Female; Ferrous Compounds; Humans; Infusions, Intravenous; Intestinal Absorption; Intracellular Fluid; Iron; Iron-Dextran Complex; Malabsorption Syndromes; Male; Mice; Mice, Mutant Strains

Topics: Anemia, Iron-Deficiency; Cytokines; Erythropoietin; Ferric Compounds; Ferritins; Humans; Iron; Renal Dialysis; Uremia

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses

Topics: Administration, Oral; Adolescent; Anemia, Iron-Deficiency; Arthritis, Juvenile; Child; Child, Preschool; Erythrocyte Count; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Ferritins; Humans; Infant; Injections, Intravenous; Interleukin-6; Iron; Iron Deficiencies; Male; Receptors, Transferrin

Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.

Topics: Administration, Oral; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Follow-Up Studies; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors

Iron deficiency is common in haemodialysis patients and adequate supplementation by the oral or parenteral route has been limited by drug side-effects, absorption, and cost. Intermittent doses of intravenous iron dextran complex are recommended in patients with inadequate iron stores despite maximal tolerated oral dose. We conducted a prospective study with economic analysis of a regular maintenance intravenous iron regimen in this group of patients.. Fifty patients comprising one-half of our haemodialysis population required intravenous iron treatment, i.e. they failed to achieve an arbitrary goal serum ferritin 100 microg/l despite maximal tolerated oral iron dose. After a loading dose of intravenous iron dextran complex (IV-FeD) based on Van Wyck's nomogram (400+/-300 mg) they received a maintenance dose of 100mg IV-FeD once every 2 weeks. Initial goal serum ferritin was set at 100-200 microg/l. If no increase in haemoglobin was achieved at this level, transferrin saturation was measured to assess bioavailable iron, and when less than 20%, goal serum ferritin was increased to 200-300 microg/l. Recombinant human erythropoietin (rHuEpo) was used where needed to maintain haemoglobin in the 9.5-10.5 g/l range only if ferritin requirements were met. Results. Mean haemoglobin rose from 87.7+/-12.1 to 100.3+/-13.1 g/l (P<0.001, Cl 7.7-17.9) at mean follow-up of 6 months (range 3-15 months). In patients on rHuEpo, dose per patient was reduced from 96+/-59 u/kg per week to 63+/-41 u/kg per week, representing a 35% dose reduction (P<0.05, Cl 1-65). An annual cost reduction of $3166 CDN was projected; however, in the first year this is offset by the cost of the loading dose of IV-FeD required at the beginning of treatment. No adverse reactions were encountered.. Iron deficiency is very common in our haemodialysis population, especially in those patients receiving rHuEpo. A carefully monitored regimen of maintenance parenteral iron is a safe, effective, and economically favourable means of iron supplementation in patients with insufficient iron stores on maximum tolerated oral supplements.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Costs and Cost Analysis; Erythropoietin; Female; Hematinics; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Ferritin and the percentage of transferrin saturation (TS) are established parameters with which to evaluate endogenous iron availability during treatment of renal anaemia with recombinant human erythropoietin (rHuEpo). Zinc protoporphyrin (ZPP) has been proposed as another valid marker in this setting.. We determined the following parameters in 127 patients, including 117 haemodialysis patients: haemoglobin, erythrocytes, haematocrit, mean corpuscular volume (MCV), iron, ferritin, transferrin saturation and ZPP. Of the patients treated in a cross-sectional study, 38.5% were treated with rHuEpo; 30.7% with intravenous iron; and 13.6% with intravenous iron and rHuEpo simultaneously. Median ferritin was 304 ng/ml and median transferrin saturation was 21.2%.. Including cases with manifest storage iron deficiency, a concordant elevated ZPP ( > 40 mumol/mol haem) and a decreased transferrin saturation ( < 20%) were found in 23 of our dialysis patients (19.6%) while 55 cases (47%) were classified as concordantly negative. However, as many as 39 cases (33.3%) showed discrepant results: in 16 cases (13.6%) ZPP was elevated but transferrin saturation was in the normal range, while in 23 cases (19.6%) the opposite results were observed.. We conclude that beyond the border of manifest storage iron deficiency, defined as a ferritin < 30 ng/ml in male and < 15 ng/ml in female patients, ZPP and TS cover different ranges of functional iron deficiency which is reflected in the lack of a correlation of ZPP to any other of the above-mentioned parameters. Our data suggest that a TS < 20% as a diagnostic, and thus intervention, criterion in the evaluation of functional iron deficiency and iron substitution beyond manifest storage iron deficiency might result in overestimation of iron requirements. It remains to be shown in a longitudinal study, also reflecting the course of haemoglobin and the mean rHuEpo dose, whether ZPP or TS is the more appropriate parameter in the evaluation of functional iron availability.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; Cross-Sectional Studies; Drug Therapy, Combination; Enzyme Inhibitors; Erythrocyte Count; Erythropoietin; Female; Ferritins; Hematocrit; Heme Oxygenase (Decyclizing); Hemoglobins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Protoporphyrins; Recombinant Proteins; Renal Dialysis; Transferrin

Case management is a multidisciplinary collaborative approach that emphasizes continuity of patient care. Nursing case management can lead to improvements in the quality of care while affording nurses the opportunity to increase their expertise, autonomy, and authority in the health care system. Treatment of the anemia of end-stage renal disease (ESRD) is used as an example to illustrate the implementation of these principles in the dialysis unit.

Topics: Anemia, Iron-Deficiency; Case Management; Critical Pathways; Erythropoietin; Female; Humans; Job Description; Kidney Failure, Chronic; Middle Aged; Models, Nursing

To investigate the hematologic and economic advantages of using iron dextran as the sole supplemental agent to safely increase and maintain hematocrit levels and iron availability while optimizing erythropoietin dosing in patients on chronic hemodialysis.. Iron dextran 100 mg (2 ml) was administered i.v. slow push, undiluted three times per week, sometime during the last 30 minutes of each hemodialysis treatment, until a total required ml (determined by using the package insert's formula) was attained. Maintenance doses of either 25 or 50 mg per week (dependent upon body weight) were administered ongoing to compensate for dialytic and gastrointestinal blood losses. The analysis duration was 12 months.. A prospective analysis was performed on 13 clinically stable hemodialysis outpatients in a rural community hospital-based dialysis facility (mean age 56.4 years ranging from 24-76; sample included 9 males, 4 females).. The means and medians were calculated for each variable: hematocrit, ferritin, transferrin saturation, and erythropoietin dose. A one-tailed paired student t test was performed on doses of erythropoietin at -1 and 6 months, -1 and 9 months, and -1 and 12 months. Cost per patient of iron dextran loading dose and maintenance, as well as cost savings from actual erythropoietin dose reductions, were calculated at 3, 9, and 12 months. Cost savings reflected the cost of iron dextran.. After 6 months on the protocol, erythropoietin doses decreased an average of 3100 units per patient with an 8% increase in hematocrit and 66% and 78% increase in transferrin saturation and ferritin, respectively. Based on averages in actual reduced erythropoietin dosing, a savings of +5,070 per patient per year was realized.. This analysis found the use of iron dextran in the hemodialysis setting to be an effective and economic means to maintain hematocrit values and iron availability while optimizing erythropoietin dosing.

Topics: Adult; Aged; Anemia, Iron-Deficiency; Cost Savings; Drug Costs; Erythropoietin; Female; Hematinics; Humans; Iron-Dextran Complex; Male; Middle Aged; Prospective Studies; Renal Dialysis

In the present study the response of plasma erythropoietin to iron injection in anaemic piglets was examined. At the age of 16 days, 4 piglets from the same litter were given 180 mg iron subcutaneously. After iron injection, blood samples for estimation of erythropoietin activity in plasma, haemoglobin concentration, and reticulocyte counts were taken every 6 or 12 h for 3 1/2 days. Plasma erythropoietin activity was estimated by a monoclonal enzyme-immunoassay (ELISA), developed for human erythropoietin. On the day of iron injection, haemoglobin concentration ranged between 41 and 48 g/l, reticulocyte counts from 9 to 17 percent, and plasma erythropoietin between 22 and 144 mU/ml. In 3 of the 4 piglets, iron injection resulted in a 2-6 fold increase in erythropoietin activity. Maximal erythropoietin activities were observed 24-42 h after injection, and after 66 h, the activities were close to the pretreatment values. It is concluded that in our experiment, iron, per se, has stimulated erythropoietin production.

Topics: Anemia, Iron-Deficiency; Animals; Erythropoietin; Hemoglobins; Iron; Swine; Swine Diseases; Time Factors

Parenteral iron abolishes the "early anaemia' in all mammals tested and increases packed cell volume (PCV) and haemoglobin concentration (Hb) significantly above adult levels. In the present study we examined the effect of parenteral iron upon serum immunoreactive erythropoietin (siEpo) concentration in young mice (age 6-24d) and in adult iron-deficient mice. Young BALB/CJ mice, from 5 to 23 d of age, and adult (60-100 d old)mice, some of which were iron deficient due to a low iron diet from the time of weaning, were given iron subcutaneously (iron sorbitol, Fe+3, 1.2 mg iron/100g body weight/injection). Iron was given as one single dose and the animals killed 20-24 h later. Control mice were similarly treated with saline. In young mice, from the age 10 d to weaning at 20 d, the siEpo level, measured 20-24 h after a single subcutaneous dose of iron, was 5 times greater than that in control mice (P < 0.0001). In contrast, there was no change in siEpo 20-24 h after a single subcutaneous dose of iron in adult mice, whether iron-deficient anaemic or normal. Thus, during the "early anaemia' in young mice over 10 d old, iron increased siEpo levels, whereas it had no such effect in iron-deficient and normal adult mice. This suggests that between ages 10 and 20 d, iron has additional effects in the regulation of erythropoiesis, which may not occur in adult or in 6-d-old mice.

Topics: Anemia, Iron-Deficiency; Animals; Erythropoietin; Female; Infusions, Parenteral; Iron; Male; Mice; Mice, Inbred BALB C

The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD.. sEPO, serum TNF-alpha, and serum gamma-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls).. Mean hemoglobin (Hgb) was 11.2 +/- 0.3 g/dl for LD patients versus 11.4 +/- 0.4 g/dl for controls (p = 0.84). sEPO levels measured by ELISA were 29.6 +/- 4.1 units/liter in LD patients versus 25.4 +/- 5.4 units/liter in controls (p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly (p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN was not detected.. These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.

Topics: Anemia; Anemia, Iron-Deficiency; Combined Modality Therapy; Cytokines; Erythropoietin; Hemoglobinometry; Humans; Liver Diseases, Alcoholic; Nutritional Status; Protein-Energy Malnutrition; Reference Values; Tumor Necrosis Factor-alpha

Red blood cell formation relies on the contributions of a variety of substances, including iron, vitamins, and protein. Therapeutic intervention with Epoetin alfa changes the requirements for these erythropoietic ingredients, frequently necessitating modifications in nutritional prescriptions. Nursing knowledge and management of the nutritional components that affect erythropoiesis can help ensure optimal patient response to therapy. Case study illustrations of iron deficiency and potassium excess are used to demonstrate potential nursing interventions.

Topics: Aged; Anemia, Iron-Deficiency; Erythropoiesis; Erythropoietin; Female; Ferrous Compounds; Humans; Kidney Failure, Chronic; Nutritional Support; Patient Compliance

Low basal hemoglobin and functional iron deficiency are the limiting factors in autologous blood donation program. Treatment with recombinant human erythropoietin can increase the volume of autologous blood and makes donation of > or = 3 units possible-even in patients with low basal hemoglobin. Best results are obtained if stimulation begins already one week before first donation.

Topics: Anemia, Iron-Deficiency; Blood Transfusion, Autologous; Erythrocyte Transfusion; Erythrocyte Volume; Erythropoietin; Hemoglobinometry; Humans; Iron; Premedication; Recombinant Proteins

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Ferritins; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Topics: Anemia, Iron-Deficiency; Blood Transfusion, Autologous; Combined Modality Therapy; Erythropoietin; Ferric Compounds; Hematinics; Humans; Infusions, Intravenous; Iron; Recombinant Proteins

Topics: Adult; Anemia, Iron-Deficiency; Erythropoietin; Humans; Intestinal Neoplasms; Leg; Lymphatic Metastasis; Male; Melanoma

Chronic anemia is frequently observed in patients affected by cirrhosis. To investigate the possible role of erythropoietin (Epo) in the pathogenesis of anemia in cirrhosis, we measured the immunoreactive Epo levels and the respective hemoglobin (Hb) concentrations in 48 anemic and nonanemic cirrhotic patients and in a control group of healthy subjects and patients with iron-deficiency anemia. Epo concentrations were determined in serum using a sensitive enzyme immunoassay. The regression curve between Epo values and Hb concentrations showed a significant inverse exponential trend both in cirrhotic patients (r = -.55; P < .0001) and controls (r = -.92; P < .0001). In a semilogarithmic plot, the line slope obtained in cirrhotic patients was significantly lower (P < .005) than that of controls, suggesting a blunt Epo response to anemia in cirrhosis. Moreover, covariance analysis showed that the Epo levels for a given degree of anemia were further reduced in the patients with a more severe disease, suggesting a close relation between cirrhosis and the mechanisms involved in the derangement of the Epo feedback system. Finally, the Epo concentrations measured in the cirrhotic patients without anemia did not significantly differ from Epo values obtained in healthy subjects. An impaired Epo response may play a role in maintaining low Hb concentrations in cirrhotic patients with anemia. However, the evidence of a residual Epo response to anemia in cirrhosis and the presence of normal basal Epo levels in nonanemic cirrhotic patients do not support an inadequate Epo secretion as one of the primary causes of anemia in cirrhosis.

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Feedback; Female; Hemoglobins; Humans; Liver Cirrhosis; Male; Middle Aged; Regression Analysis

Topics: Administration, Oral; Anemia; Anemia, Iron-Deficiency; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Ferrous Compounds; Humans; Inflammatory Bowel Diseases; Injections, Subcutaneous; Recombinant Proteins

The purpose of this study was to evaluate the sensitivity and specificity of laboratory methods in the diagnosis of posterythropoietin-era, iron-deficient, chronic renal failure patients. The patient population comprised 25 anemic (hemoglobin < 11 g/dL) patients with creatinine greater than 3 mg/dL; 20 were dialysis patients, two were transplant patients, and three patients had renal failure from other causes. Criteria for study inclusion were as follows: bone marrow iron was the reference standard and was graded 0 to +4, ranging from absent to diffuse homogeneous iron staining; serum ferritin concentration and serum transferrin saturation were tested in terms of sensitivity and specificity. The reference standard indicated that iron deficiency existed in 40% of patients. Neither serum ferritin nor transferrin saturation were completely adequate diagnostic tools. Serum ferritin levels less than 200 ng/dL were 100% specific for the diagnosis but only 41% sensitive. Transferrin saturation of less than 20% was 88% sensitive, but only 63% specific. By excluding patients with hypoproteinemia (transferrin values of < 150 mg/dL), the sensitivity of the test increased to 100% and the specificity to 80%. We conclude that transferrin saturation is an adequate screening tool in anemic chronic renal failure patients, provided that hypoproteinemia is not present. By determining both the serum ferritin concentration and the transferrin saturation, a high sensitivity and specificity can be achieved, even in patients with hypoproteinemia. Furthermore, we believe that on this basis, iron therapy in patients with renal insufficiency can be improved.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Bone Marrow; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Transferrin

The optimal method for diagnosing iron deficiency in end-stage renal disease is an area of controversy. This study compared the use of zinc protoporphyrin (ZPP) with the use of conventional tests for determination of iron deficiency when evaluating the need for intravenous iron therapy in hemodialysis patients maintained on erythropoietin (EPO). A baseline survey was performed in all hemodialysis patients at the Baumritter Kidney Center (Bronx, NY), measuring ZPP, ferritin, transferrin saturation (TSAT), mean corpuscular volume, and hematocrit. Patients with ZPP > or = 90 mumol/mol heme or ferritin less than 100 ng/mL were considered likely to be iron deficient and were treated with 1,000 mg of intravenous iron dextran over 10 hemodialysis treatments. The positive predictive values of ferritin and ZPP for predicting a response to intravenous iron dextran were similar (73% v 83%, respectively; two-tailed, P = 0.48). To determine the sensitivity and specificity of the tests, patients were divided into two groups at the end of the study period: those in whom iron therapy was required (n = 23) (patients treated with intravenous iron dextran who had a 5% increase in hematocrit or a decrease in erythropoietin dose of > or = 2,000 U/treatment) and those in whom iron therapy was not required (n = 24) (patients either treated with intravenous iron dextran without a response [n = 9] or patients whose initial ZPP and ferritin levels were not suggestive of iron deficiency and who maintained a stable hematocrit and erythropoietin dose during the study period [n = 15]).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anemia; Anemia, Iron-Deficiency; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Protoporphyrins; Renal Dialysis; Sensitivity and Specificity; Transferrin

Serum erythropoietin (EPO) and soluble transferrin receptor levels were serially measured in 74 patients with aplastic anaemia (AA). As control groups we investigated healthy controls (n = 24) and patients with iron-deficiency (n = 23) or haemolytic anaemia (n = 16). There was a significant negative correlation of log EPO on haematocrit both in AA patients and in the anaemic control group. However, for the same degree of anaemia, log EPO levels in AA were significantly higher than in iron-deficiency or haemolytic anaemia. EPO levels at diagnosis did not correlate with severity of aplastic anaemia, nor did they predict outcome after immunosuppression. During immunosuppressive treatment of AA with anti-thymocyte globulin and cyclosporine A, EPO levels were significantly lower compared with pre-treatment values without a corresponding change in haematocrit. This impaired EPO response to anaemia during immunosuppression might affect recovery of erythropoiesis. In AA patients, EPO levels declined with haemopoietic recovery. However, compared with normal controls, EPO levels in remission patients were still higher with respect to their haematocrit. Results of this study argue against the model of a simple feedback regulation of EPO via hypoxic anaemia. Our data support the hypothesis that cytokines and the erythropoietic progenitor pool are involved in the regulation of EPO production. The results illustrate that serial measurements of EPO along with therapeutic interventions are necessary to identify patients who might benefit from treatment with exogenous recombinant human EPO.

Topics: Adolescent; Adult; Age Factors; Aged; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Immunosuppression Therapy; Male; Middle Aged; Receptors, Transferrin; Sex Factors; Treatment Outcome

Studies were performed to reexamine the response of erythropoietin (Epo) production to acute hypoxic stimuli in patients with end-stage renal disease (ESRD). In the absence of acute bleeding or hypoxia, the serum Epo level in ESRD was similar to that of normal subjects despite severe anemia. In 11 dialysis patients with acute bleeding, the decrease in the Hb level from 8.9 to 5.8 g/dL provoked a significant increase in serum Epo up to 52.2 times the normal value. The increase in serum Epo was associated with a significant increase in corrected reticulocyte. Systemic hypoxemia (PaO2 < 65 mm Hg) in 8 dialysis patients provoked a significant elevation in the serum Epo level up to 24.6 times the normal level. There was an inverse relationship between serum Epo and arterial PaO2 (r = -0.715). The serum Epo level in these patients declined to or near the normal value after recovery from acute hypoxic stress. These data suggest that the ability of the Epo production is well preserved in ESRD, indicating that acute hypoxic stimuli provoke a significant increase in serum Epo.

Topics: Acute Disease; Adult; Aged; Anemia, Iron-Deficiency; Erythropoietin; Female; Hemoglobins; Hemorrhage; Humans; Hypoxia; Kidney Failure, Chronic; Male; Middle Aged; Oxygen; Partial Pressure; Renal Dialysis

Patients with malignant disease frequently develop anaemia. To investigate the role of erythropoietin (EPO) in this anaemia, serum levels were determined in patients with solid tumours. The study population consisted of 84 patients (44 males, 40 females) with solid tumours and 99 healthy control subjects, and 13/84 patients were anaemic. Serum EPO was clearly elevated in the anaemic tumour patients, but this increase was less than in patients suffering from iron deficiency anaemia. As in iron deficiency anaemia, the correlation between EPO levels and haemoglobin values was inverse. When compared to healthy control subjects, the levels of EPO in the tumour patients without anaemia were decreased. We conclude that there may be an inhibition in the expression or secretion of EPO in patients with solid tumours which, as yet, has not been further defined. Based on this, the treatment of anaemia in cancer patients with erythropoietin appears promising.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Erythropoietin; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Hemoglobins; Humans; Iron; Male; Melanoma; Middle Aged; Sex Factors; Transferrin

Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Anemia, Macrocytic; Blood Platelets; Bone Marrow Cells; Drug Therapy; Epoetin Alfa; Erythropoietin; FIGLU Test; Folic Acid; Folic Acid Deficiency; Glutamates; Hemoglobins; Humans; Infant; Infusions, Parenteral; Injections, Intravenous; Iron; Iron-Dextran Complex; Megakaryocytes; Reticulocytes; Thrombocytopenia; Thrombocytosis; Vitamin B 12