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erythropoiesis review

Yu Seob Shin, Jae Hyung You, Jai Seong Cha, Jong Kwan Park
OBJECTIVE: To investigate the relationship between serum total testosterone (TT) and free testosterone (FT) levels in men with anemia. METHODS: We reviewed the records of 1221 subjects between March 2009 and December 2014. All the subjects' blood samples were drawn for TT and FT assays. Their serum hemoglobin (Hb) and serum hematocrit (Hct) levels were measured. The primary objective of our study was to investigate the association between TT and FT levels with Hb and Hct levels...
October 18, 2016: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
S D Roger, M Tio, H C Park, H L Choong, B Goh, T R Cushway, V Stevens, I C Macdougall
AIM: Higher dosages of erythropoiesis-stimulating agents (ESAs) have been associated with adverse effects. Intravenous iron is used to optimise ESA response and reduce ESA doses in haemodialysis patients; this meta-analysis evaluates the magnitude of this effect. METHODS: A literature search was performed using MEDLINE, Embase and the Cochrane Collaboration Central Register of Clinical Trials from inception until December 2014, to identify randomised controlled trials (RCTs) of intravenous iron and ESA, in patients undergoing haemodialysis for end-stage kidney disease...
October 3, 2016: Nephrology
Tyler Albright, Akram Al-Makki, Rabih Kalakeche, Brian Shepler
PURPOSE: The objective of this short review is to evaluate the efficacy of ferric pyrophosphate citrate and to determine its place in therapy based on the current published literature. METHODS: A literature search was conducted and pared down to yield 4 placebo controlled Phase II and III clinically relevant trials. FINDINGS: Ferric pyrophosphate citrate is a new intradialytic iron supplementation product that has been found to reduce the dose of erythropoiesis-stimulating agents and intravenous iron supplementation and to increase serum ferritin concentrations...
September 27, 2016: Clinical Therapeutics
Jean-Benoît Arlet, Flavia Guillem, Mathilde Lamarque, Michael Dussiot, Thiago Maciel, Ivan Moura, Olivier Hermine, Geneviève Courtois
Major advances have been recently made in understanding the molecular determinants of dyserythropoiesis, particularly due to recent works in β-thalassemia. The purpose of this review is devoted to underline the role of some proteins recently evidenced in the field, that may be new alternative therapeutic targets in the near future to alleviate different types of anemia. Areas covered: This review covers the contemporary aspects of some proteins involved in various types of dyserythropoiesis, including the transcriptional factor GATA-1 and its protective chaperone HSP70, but also cytokines of the transforming growth factor beta (TFG-β) family, TGF-β1 and GDF-11, and hormones as erythroferrone...
October 6, 2016: Expert Review of Proteomics
Andras T Deak, Katharina Troppan, Alexander R Rosenkranz
Anemia is a common complication of cancer and chronic kidney disease (CKD) associated with decreased physical performance as well as poor prognosis for life expectancy. Renal and cancer-induced anemia share common features regarding pathogenesis and therapeutic strategies. It is typically treated with iron substitution, erythropoiesis-stimulating agents (ESA) and in refractory cases with red blood cell transfusions. However, studies of the past few years unveiled numerous setbacks in the use of ESAs. These included a higher risk of cerebrovascular events and increased mortality without the improvement of cardiovascular outcomes in patients with CKD...
September 15, 2016: European Journal of Internal Medicine
Yufang Zhang, Weiwei Chen, Yuanyuan Wu, Bin Yang
The renoprotection of erythropoietin (EPO) and its derivatives such as helix B surface peptide (HBSP) have attracted a great deal of attention from scientists and clinicians alike. The evolutional achievement in the dissociation of tissue protection and erythropoiesis is obtained through HBSP characterisation and synthesis. We performed a series of studies using EPO mostly, as well as HBSP, in a variety of biological models subjected to transplant-related renal injuries such as ischemia reperfusion injury (IRI) and/or immunosuppressant nephrotoxicity...
September 9, 2016: Current Protein & Peptide Science
Anna Mies, Olivier Hermine, Uwe Platzbecker
Distinct subtypes of lower risk myelodysplastic syndromes display ring sideroblasts in the bone marrow, i. e., erythroid progenitors characterized by excessive iron deposited in the mitochondria. This morphological feature is frequently associated with somatic mutations in components of the splicing machinery that constitutes the underlying molecular principle of the disease. Conventional treatment regimen with erythropoiesis-stimulating agents often fails to induce sustained erythroid improvement in these patients that harbor defects in late-stage erythroblasts downstream of erythropoietin action...
September 5, 2016: Current Hematologic Malignancy Reports
Manfred Nairz, Igor Theurl, Dominik Wolf, Günter Weiss
Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen...
October 2016: Wiener Medizinische Wochenschrift
Terhi Hermanson, Charles L Bennett, Iain C Macdougall
INTRODUCTION: The introduction of recombinant human erythropoietin revolutionized the management of anemia in patients with chronic kidney disease (CKD). In order to circumvent costly recombinant DNA technology, synthetic chemistry techniques were used to manufacture peginesatide, a synthetic peptide that bore no resemblance to previous erythropoiesis-stimulating agents (ESAs), and yet was capable of stimulating erythropoiesis. Compared with other ESAs, peginesatide was deemed to have advantages related to immunogenicity, administration schedule, and cost...
October 2016: Expert Opinion on Drug Safety
Thomas Prebet, Amer Zeidan
Myelodysplastic syndrome (MDS) paradigms have been dramatically changed over the last 10 years by major breakthroughs on both pathophysiologic and therapeutic aspects. It is currently a field of intense clinical investigation as new challenges have emerged in both low-risk and high-risk populations. In low-risk MDS, long-term control of anemia is a major issue, and second-line treatments after failure of erythropoiesis-stimulating agents are warranted. Several promising therapies are available, and there are many open questions on how to select the most adapted agent and/or sequence of agents in a specific individual...
August 2016: Clinical Lymphoma, Myeloma & Leukemia
Bhupesh Panwar, Orlando M Gutiérrez
Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD...
July 2016: Seminars in Nephrology
Linda M S Resar, Elizabeth C Wick, Talal Nael Almasri, Elizabeth A Dackiw, Paul M Ness, Steven M Frank
BACKGROUND: Advances in our understanding of the risks associated with allogeneic blood transfusions (ABTs) and the growing number of patients who wish to avoid ABTs have led to the emergence of new treatment paradigms for "bloodless" medicine and surgery. STUDY DESIGN AND METHODS: Here, we review prior studies and summarize current strategies for bloodless care used at our institution. We advocate three basic principles: 1) diagnosing and aggressively treating anemia, 2) minimizing blood loss from laboratory testing and invasive procedures, and 3) identifying and managing bleeding diatheses...
October 2016: Transfusion
R R Pate
In brief: A small percentage of athletes are anemic, and a substantial number have hemoglobin concentrations that are less than optimal for endurance performance. Possible causes of sports anemia are plasma volume expansion, reduced hemoglobin synthesis and/or erythropoiesis, and increased destruction of RBCs. Physicians should screen athletes for anemia, suboptimal hemoglobin, and the factors that apparently increase the risk of these conditions: (1) a diet that is low in iron, protein, vitamin C, vitamin B12, and/or folic acid; (2) high rates of iron loss; and (3) very intense training, especially at the outset of an exercise program...
February 1983: Physician and Sportsmedicine
Giada Sebastiani, Nicole Wilkinson, Kostas Pantopoulos
The iron regulatory hormone hepcidin limits iron fluxes to the bloodstream by promoting degradation of the iron exporter ferroportin in target cells. Hepcidin insufficiency causes hyperabsorption of dietary iron, hyperferremia and tissue iron overload, which are hallmarks of hereditary hemochromatosis. Similar responses are also observed in iron-loading anemias due to ineffective erythropoiesis (such as thalassemias, dyserythropoietic anemias and myelodysplastic syndromes) and in chronic liver diseases. On the other hand, excessive hepcidin expression inhibits dietary iron absorption and leads to hypoferremia and iron retention within tissue macrophages...
2016: Frontiers in Pharmacology
Marianne Heibert Arnlind, Linda Fryklund, Sigurd Vitols, Göran Bertilsson
PURPOSE: We systematically reviewed published observational studies and randomized controlled trials (RCT) reports of clinical trials on erythropoiesis-stimulating agents (ESA's). Only studies evaluating the risk of developing anti-drug antibodies (ADA) of both original and biosimilar drugs were chosen. METHODS: Databases including PubMed, EMBASE and Cochrane Library were searched up to 17 March 2015. Two reviewers independently assessed the relevant studies for risk of bias...
October 2016: European Journal of Clinical Pharmacology
Kai Zacharowski, Donat R Spahn
Patient blood management (PBM) can be defined in many ways and may consist of hundreds of single measures to improve patient safety. Traditionally, PBM is based on three pillars and defined as (i) optimization of the endogenous red blood cell (RBC) mass through the targeted stimulation of erythropoiesis and the treatment of modifiable underlying disorders; (ii) minimization of diagnostic, interventional, and surgical blood loss to preserve the patient's RBC mass; and (iii) optimization of the patient-specific tolerance to anemia through strict adherence to physiological transfusion thresholds [1-4]...
June 2016: Best Practice & Research. Clinical Anaesthesiology
Wolfgang Jelkmann
Total hemoglobin (Hb) mass is an important determinant of aerobic power. The glycoprotein erythropoietin (Epo) promotes the production of red blood cells (RBCs). The present article reviews the regulation of erythropoiesis and ways of its manipulation. The various Epos, e.g. recombinant human (rh)Epo and (epoetin), and their long-acting analogues can be misused by cheating athletes, but the drugs are detectable by chemical tests, because their glycan isoform structures differ from those of endogenous Epo. Still, anti-doping control has become more difficult, since additional erythropoiesis-stimulating agents have become available (Epo mimetics, activin inhibitors, and small-molecule chemical drugs activating EPO expression)...
2016: Frontiers of Hormone Research
Daniel Shepshelovich, Benaya Rozen-Zvi, Tomer Avni, Uzi Gafter, Anat Gafter-Gvili
BACKGROUND: Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial. STUDY DESIGN: Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials...
June 16, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Yalcin Solak, Mustafa Cetiner, Dimitrie Siriopol, Kayhan Tarim, Baris Afsar, Adrian Covic, Mehmet Kanbay
Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population...
2016: Blood Purification
Hitesh H Shah, Azzour D Hazzan, Steven Fishbane
Management of anemia remains an integral component in the care of patients with chronic kidney disease undergoing hemodialysis. In addition to erythropoiesis-stimulating agents, iron-replacement agents remain a key strategy for anemia treatment in this patient population. Ferric pyrophosphate citrate (FPC), a novel iron-replacement agent, was approved by the US Food and Drug Administration in January 2015 for use in adult patients receiving chronic hemodialysis (HD). This iron product is administered to patients on HD via the dialysate...
March 2016: Seminars in Nephrology
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