losartan-potassium and Syndrome

Cancer patients frequently present with anaemia that may result from the direct or indirect effects of the tumor or its treatment. Anaemia is an independent adverse prognostic factor that exerts negative influence on quality of life and survival of cancer patients. Anaemia in malignant disorders often arises from an interplay of multiple aetiological and pathophysiologic mechanisms. Understanding these mechanisms will help the oncologist identify and treat specific causes of the anaemia thereby minimizing the use of blood transfusion, which is associated with many adverse effects. This paper reviewed the various aetiological and pathophysiologic mechanisms of anaemia in cancer patients including direct and indirect tumour effects that lead to reduced red cell production or increased red cell destruction via a myriad of mechanisms ranging from marrow infiltration and cancer-associated acute myelonecrosis to chronic inflammation, blood loss, iron, folate, vitamin B12 and other nutrients deficiencies, malignancy related renal injury, pure red cell aplasia, hypersplenism, haemophagocytic syndrome, red cell autoantibody production, non-immune red cell fragmentation and cytotoxic therapy-induced erythroid cell apoptosis and eryptosis. Hence anaemia in cancer patients is attributable to a wide spectrum of aetiological factors with multiple and sometimes overlapping pathophysiologic mechanisms. It is therefore necessary for the oncologists to thoroughly investigate all cases of anaemia with the aim of identifying the actual causative factors in order to offer more sustainable cause-specific treatment modalities that will minimize the use of blood transfusion with its attendant adverse effects.

Topics: Anemia; Bone Marrow Transplantation; Erythropoietin; Humans; Neoplasms; Quality of Life; Syndrome

The relationships between erythropoietin (EPO), iron, and erythropoiesis and the presence of iron-restricted erythropoiesis have important implications in anemia management. Iron-restricted erythropoiesis occurs in the presence of one or more iron deficiency syndromes: absolute iron deficiency, functional iron deficiency, and/or iron sequestration. Absolute iron deficiency is a common nutritional deficiency in women's health, pediatrics, and the elderly and is therefore an important public health problem. Functional iron deficiency occurs in patients with significant EPO-mediated erythropoiesis or therapy with erythropoiesis-stimulating agents, even when storage iron is present. Iron sequestration mediated by hepcidin is an underappreciated but common cause of iron-restricted erythropoiesis in patients with chronic inflammatory disease. The challenge for treating and laboratory-based physicians is to understand the contributory role(s) of each of these syndromes, so that the potential value of emerging and innovative pharmacologic strategies can be considered as options in patient blood management.

Topics: Aged; Antimicrobial Cationic Peptides; Child; Child, Preschool; Chronic Disease; Erythropoiesis; Erythropoietin; Female; Hepcidins; Humans; Infant; Inflammation; Iron; Iron Deficiencies; Iron Metabolism Disorders; Male; Middle Aged; Syndrome

Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the 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. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, 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 the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.

Topics: Anemia; Bone Marrow; Cardiovascular System; Clinical Trials as Topic; Erythropoietin; Heart Failure; Hematinics; Humans; Infusions, Intravenous; Iron; Iron Deficiencies; Kidney; Outcome Assessment, Health Care; Renal Insufficiency, Chronic; Syndrome; Trace Elements

Anemia is a disease that is often associated with heart failure (HF) and renal insufficiency (RI). This unfavorable triad of conditions has been called Cardio-Renal-Anemia Syndrome (CRS). The association of HF, RI, and anemia is poorly reported in multicenter clinical trials, so the pathophysiologic mechanisms and treatment options need to be better defined. When CRS patients develop anemia, a "perfect storm" often occurs: HF and RI cause anemia which will worsen the first two conditions. Anemia appears to be the result of complex interactions between cardiac performance, bone marrow homeostasis, renal dysfunction, and various drug side effects. However, neurohormonal and inflammatory activities play a key role in the beginning and progression of the disease. As a consequence, endogenous erythropoietin activity dysfunction with inadequate production and tissue resistance occurs. Despite the advances of therapy in the neurohormonal activation blockade, mortality and hospitalization in HF still remain unacceptably high, suggesting that specific comorbidity treatments could have a significant positive prognostic impact. Anemia should be recognized as one of the novel targets in HF treatment.

Topics: Anemia; Bone Marrow; Cardiovascular System; Clinical Trials as Topic; Disease Progression; Drug Therapy, Combination; Erythropoietin; Heart Failure; Hemoglobins; Humans; Iron; Patient Selection; Prognosis; Renal Insufficiency; Risk Factors; Severity of Illness Index; Syndrome; Water-Electrolyte Balance

Our understanding of organismal responses to hypoxia has stemmed from studies of erythropoietin regulation by hypoxia that led to the discovery of the master regulator of the hypoxic response, i.e., hypoxia-inducible factor (HIF). This is a transcription factor that is now known to induce the expression of a battery of genes in response to hypoxia. HIF-1 and HIF-2 regulate many genes that are involved in erythropoiesis and iron metabolism, which are essential for tissue oxygen delivery.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Brain; Cell Hypoxia; Cell Lineage; Erythropoietin; Hematopoiesis; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Iron; Kidney; Liver; Oxygen; Pluripotent Stem Cells; Protein Isoforms; Syndrome

Sudden cardiac arrest is a leading cause of death worldwide with survival rates still remaining suboptimal. Unfortunately, most cardiac arrest patients, who achieve return of spontaneous circulation (ROSC), develop a multi-faceted post-cardiac arrest syndrome, including post-cardiac arrest brain injury, myocardial dysfunction, and systemic ischemia/reperfusion response. Erythropoietin (EPO), the principal hematopoietic hormone regulating erythropoiesis, exhibits diverse cellular effects in nonhematopoietic tissues. Due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, as well as its angiogenic action, EPO plays a role in neuroprotection and cardioprotection. In this regard, EPO represents a promising agent in the cardiac arrest setting, based on a therapeutic strategy that focuses on the post-resuscitation phase. This review aims to provide a comprehensive account of EPO's role in the treatment of each individual component of post-cardiac arrest syndrome.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Diseases; Cardiomyopathies; Cardiotonic Agents; Erythropoietin; Heart Arrest; Humans; Reperfusion Injury; Syndrome

Erythropoietin (EPO) is a hematopoietic hormone with extensive nonhematopoietic properties. The discovery of an EPO receptor outside the hematopoietic system has fuelled research into the beneficial effects of EPO for various conditions, predominantly in cardiovascular disease. Experimental evidence has revealed the cytoprotective properties of EPO, and it seems that the EPO-EPO receptor system provides a powerful backbone against acute myocardial ischemia, gaining from the different properties of EPO. There is an ongoing discussion about possible discrepancy between preclinical and clinical effects of EPO on the cardiovascular system. Large, randomized, placebo-controlled clinical trials are underway to give a final verdict on EPO treatment for acute coronary syndromes.

Topics: Acute Coronary Syndrome; Acute Disease; Anemia; Erythropoiesis; Erythropoietin; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Receptors, Erythropoietin; Syndrome

The pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has been denoted as severe cardiorenal syndrome (SCRS). An interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide (NO) and reactive oxygen species (ROS) balance, the sympathetic nervous system (SNS), and inflammation, has been proposed as the cornerstones of the pathophysiology of SCRS. Because erythropoietin (Epo) production declinesin chronic renal failure (CRF) and Epo sensitivity might decrease by the cardiorenalconnectors in patients with the SCRS, it is not surprising thatanaemia is a commonly occurring state coinciding with CRF and chronic heart failure (CHF). Epo treatment in patients with SCRS acts via haematopoietic effects, but also may intervenes in the vicious circle of cardiorenal connectors with subsequent deteriorating effects on cardiac, renal, and vascular function. It appears that regular Epo treatment in anaemic patients with diminished renal function improves cardiac performance, delays the progression of kidney disease, and may be of clinical benefit even to patients suffering from CHF with relatively mild anaemia. Despite growing evidence about Epo having positive effects on both renal and cardiac function, little is known about the underlying mechanisms of action.

Topics: Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Syndrome

The triad of chronic kidney disease, heart failure and anemia is well described and frequently encountered in clinical practice. While individually these disease states are associated with significant morbidity and mortality, the presence of the triad portends an even worse prognosis. Anemia is prevalent among cohorts of patients with chronic kidney disease and heart failure, indicating that its presence may serve as a central unifying hypothesis to explain poor outcomes in these populations. Observational and interventional trials of erythropoietin-stimulating agents, however, have had variable results on cardiovascular end points. Data are now emerging that suggest that treating erythropoietin deficiency in and of itself may be as or more important than the absolute levels of hemoglobin attained. Future research in this arena must focus on the optimal dose of erythropoietin administered to hemoglobin level achieved that will result in improved cardiovascular outcomes for patients with heart failure and kidney disease.

Topics: Anemia; Comorbidity; Erythropoiesis; Erythropoietin; Female; Forecasting; Heart Failure; Humans; Kidney Failure, Chronic; Male; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Survival Analysis; Syndrome

Chronic kidney disease (CKD) is now recognized as a risk factor of both end-stage renal disease (ESRD) and independently cardiovascular disease (CVD). Therefore, a specific renoprotective intervention is strongly recommended, including blood pressure control as well as anemia improvement with erythropoietin stimulating agents (ESAs). Treatment of renal anemia with ESAs has been proved to improve quality of life (QOL) and finally reduce patient mortality. Recently, Silverberg, et al. created a novel clinical entity of Cardio-Renal Anemia (CRA) syndrome, in which anemia plays a key role for worsening both CKD and cardiac performance in a vicious circle. An appropriate and vigorous treatment of anemia has now been accepted to terminate or weaken the circle. Recently, two large-scaled randomized controlled trials were reported, being the CREATE (cardiovascular risk reduction by early anemia treatment with epoetin beta) study and the CHOIR (correction of hemoglobin and outcomes in renal insufficiency) study. They demonstrated that early initiation of ESA treatment and targeting at higher hemoglobin level (near normal level) failed to show the lowering effects for cardiovascular events as compared to a group in which Hb targeting was lower (sub-normal level) in pre-dialysis CKD patients. While there has been many argues in these reports especially about baseline patients characteristics, being a quite high incidence of severe cardiovascular co-morbidity. Thus, further evidences should be accumulated to resolve a proper target level of Hb in ESA treatment.

Topics: Anemia; Cardiovascular Diseases; Chronic Disease; Disease Progression; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Diseases; Kidney Failure, Chronic; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Syndrome

Although many studies have found a high prevalence of anaemia in patients with congestive heart failure (CHF), few have carefully examined the relationship between the CHF and the prevalence of anaemia and chronic renal insufficiency (CRI). Patients with advanced renal failure, significant anaemia, diffuse atherosclerosis, respiratory disease and more elderly patients have been systematically excluded from the great majority of the randomised clinical trials.. Both anaemia and renal insufficiency are very common associated diseases associated with increased mortality, morbidity and rate of hospitalisation in CHF patients. Impaired renal function is associated with adverse outcomes because it represents a marker of coexistent disease and more diffuse atherosclerosis. In patients with CHF, progressive renal dysfunction leads to a decrease in erythropoietin (EPO) levels with reduced erythrocyte production from bone marrow. This may explain the common association between CHF, anaemia and CRI in clinical practice. The normalisation of haemoglobin concentration by EPO in patients with CHF and CRI results in improved exercise capacity by increasing oxygen delivery and improving cardiac function.. In this review, we describe the mechanisms linking anaemic status, CRI and CHF, the prognostic relevance of each disease, treatment implications, and potential benefit of EPO administration.

Topics: Anemia; Erythropoietin; Heart Failure; Humans; Iron; Kidney Failure, Chronic; Prognosis; Syndrome

Topics: Adrenal Cortex Hormones; Angioedema; Blood Component Transfusion; Brain Edema; Cyclosporins; Endothelium, Vascular; Erythropoietin; Humans; Hypertensive Encephalopathy; Immunosuppressive Agents; Magnetic Resonance Imaging; Seizures; Syndrome

Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, poor quality of life (QoL), progressive chronic kidney disease (CKD) which can lead to end stage kidney disease (ESKD), or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these people is the fact that they are often anemic. The anemia in CHF is due mainly to the frequently-associated CKD but also to the inhibitory effects of cytokines on erythropoietin production and on bone marrow activity, as well as to their interference with iron absorption from the gut and their inhibiting effect on the release of iron from iron stores. Anemia itself may further worsen cardiac and renal function and make the patients resistant to standard CHF therapy. Indeed anemia in CHF has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, the need for higher doses of diuretics, progressive worsening of renal function and reduced QoL. In both controlled and uncontrolled studies of CHF, the correction of the anemia with erythropoietin (EPO) and oral or intravenous (IV) iron has been associated with improvement in many cardiac and renal parameters and an increased QoL. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia--by reducing apoptosis of cardiac and endothelial cells, increasing the number of endothelial progenitor cells, and improving endothelial cell function and neovascularization of the heart. Anemia may also play a role in the worsening of acute myocardial infarction and chronic coronary heart disease (CHD) and in the cardiovascular complications of renal transplantation. Anemia, CHF and CKD interact as a vicious circle so as to cause or worsen each other- the so-called cardio renal anemia syndrome. Only adequate treatment of all three conditions can prevent the CHF and CKD from progressing.

Topics: Anemia; Cardiology; Chronic Disease; Erythropoietin; Heart Failure; Humans; Interdisciplinary Communication; Iron; Kidney Diseases; Nephrology; Syndrome

The anemia of chronic disease (ACD) is a hypoproliferative anemia defined by a low serum or plasma iron concentration in the presence of adequate reticuloendothelial iron stores. It is been established that ACD results from the effects of cytokines that mediate the immune or inflammatory response. During the past 3 years, the clinical scope of this syndrome has been expanded beyond the traditional chronic infectious, inflammatory, or neoplastic diseases to include other, often acute, syndromes in which the same pathogenetic mechanisms are operating. An improved understanding of the use of the soluble transferrin receptor concentration in clinical medicine has enhanced the ability to diagnose ACD, and further experience with the use of recombinant human erythropoietin in the management of severely affected patients with ACD has provided a basis for rational and effective management. Ongoing studies of the mechanisms contributing to the development of ACD continue to elucidate the pathogenesis of this common and clinically significant syndrome.

Topics: Anemia; Chronic Disease; Erythropoietin; Humans; Receptors, Transferrin; Syndrome

Sickle cell disease is numerically as common as thalassaemia. However, it affects relatively under privileged population i.e. tribal population belonging to economically poor class and having inadequate access to education and modern health facilities. A recent explosion acknowledged in understanding the pathogenesis of this disease has lead to newer dimensions in treatment. Some of these viz. prevention of overwhelming bacterial infection, present indications and controversies regarding blood transfusion, prevention of stroke, acute chest syndrome, hydroxyurea therapy--probably the best disease modifying agent at the moment, stem cell transplantation--a cure and certain promising experimental therapies including gene therapy have been discussed in this review.

Topics: Acute Disease; Adolescent; Anemia, Sickle Cell; Antisickling Agents; Bacterial Infections; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Humans; Hydroxyurea; Infant; Infant, Newborn; Recombinant Proteins; Respiratory Tract Diseases; Stem Cell Transplantation; Stroke; Syndrome

Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.

Topics: Acute-Phase Reaction; Anemia; Chronic Disease; Erythropoietin; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Protein-Energy Malnutrition; Quality of Life; Recombinant Proteins; Renal Dialysis; Syndrome; Wasting Syndrome

The anemia found in patients with chronic infectious, inflammatory, and neoplastic disorders, known as the anemia of chronic disease (ACD), is one of the most common syndromes in medicine. A characteristic finding of the disorders associated with ACD is increased production of the cytokines that mediate the immune or inflammatory response, such as tumor necrosis factor, interleukin-1, and the interferons. All the processes involved in the development of ACD can be attributed to these cytokines, including shortened red cell survival, blunted erythropoietin response to anemia, impaired erythroid colony formation in response to erythropoietin, and abnormal mobilization of reticuloendothelial iron stores. In this review, advances in the understanding of the diagnostic, pathophysiologic, and therapeutic aspects of this syndrome are summarized.

Topics: Anemia; Cell Survival; Chronic Disease; Cytokines; Diagnosis, Differential; Erythrocytes; Erythropoietin; Humans; Inflammation; Syndrome

Topics: Erythropoietin; Hematuria; Humans; Kidney Diseases; Low Back Pain; Nephrectomy; Renal Dialysis; Syndrome

Topics: Anemia, Aplastic; Animals; Bone Marrow Cells; Cell Differentiation; Cell Division; Cells, Cultured; Clone Cells; Colony-Forming Units Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Hematologic Diseases; Hemoglobins; Humans; Immunosuppression Therapy; Mice; Myeloproliferative Disorders; Syndrome; T-Lymphocytes; Time Factors

Topics: Diagnosis, Differential; Erythropoietin; Hemangiopericytoma; Hormones, Ectopic; Humans; Hypertension, Renal; Hyperthyroidism; Kidney Neoplasms; Paraneoplastic Endocrine Syndromes; Renin; Syndrome; Wilms Tumor

Topics: Adrenocorticotropic Hormone; Chorionic Gonadotropin; Erythropoietin; Gastrins; Genetic Code; Gonadotropins, Pituitary; Hormones; Humans; Insulin; Insulin Secretion; Melanocyte-Stimulating Hormones; Neoplasms; Serotonin; Skin; Skin Neoplasms; Syndrome

Patients with cardiorenal syndrome (CRS) have high cardiovascular morbidity. Endothelial progenitor cells (EPC) constitute an endogenous vascular repairsystem, protecting against atherosclerosis development. Erythropoietin (EPO) treatment may have beneficial effects by mobilizing EPC from the bonemarrow. Our objective is to determine EPC levels and effects of EPO therapy on EPC levels in CRS patients.. Open-label randomized trial.. Part of the EPOCARES-trial, conducted in Utrecht (Netherlands).. Patients with CRS and anaemia and healthy controls were included. Interventions Patients were randomized to receive EPO therapy (50 IU/kg/wk) for 52 weeks or no EPO therapy.. CD34(+)KDR(+)-EPC, cultured EPC outgrowth and function at baseline, after 18 days and after 52 weeks.. Patients showed lower CD34(+)KDR(+)-cell numbers compared to controls (6(12) vs. 19(19) cells/10(5) granulocytes; p = 0.010), despite increased levels of stromal cell-derived factor-1α; (3.1(0.8) vs 2.6(0.3) ng/ml; p = 0.001). EPC outgrowth and function were not different between patients and controls. EPC levels did not change after 18 days with or without EPO treatment. CD34(+)KDR(+)-cells significantly declined after 52 weeks in the non-treated group (p = 0.028). Long-term EPO therapy did not significantly affect this reduction in CD34(+)KDR(+)-EPC levels.. CRS patients showed reduced CD34(+)KDR(+)-EPC levels compared to controls, consistent with a reduced vascular regenerative potential and despite upregulated SDF-1α levels. Over a one-year follow-up period a marked 68% further reduction in EPC levels was observed in the patient group without EPO treatment. In spite of promising experimental studies, our longitudinal, randomized study did not show significant influence of either short- or long-term EPO therapy on reduced EPC levels in CRS patients.

Topics: Anemia; Antigens, CD34; Cell Count; Cell Proliferation; Chemokine CXCL12; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Recombinant Proteins; Stem Cells; Syndrome

Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias.. Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion.. In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P = 0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count.. This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production.

Topics: Adolescent; Adult; Aged; Anemia, Sickle Cell; Antimicrobial Cationic Peptides; beta-Thalassemia; Biomarkers; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Female; Gene Expression Regulation; Hepcidins; Humans; Iron; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Reticulocyte Count; Syndrome

Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its correction with erythropoietin (EPO) on cardiac structure and function.. The present study examines in patients with advanced CHF, chronic renal insufficiency, and anemia the effects of beta-EPO on left ventricular (LV) systolic diameter and volume (LVSD and LVSV), LV diastolic diameter and volume (LVDD and LVDV), LV mass, LV ejection fraction (LVEF), pulmonary artery pressure (PAP), and B-type natriuretic peptide (BNP) levels.. Fifty-one consecutive subjects affected with advanced CHF and anemia were studied. We performed a randomized double-blind controlled study of correction of anemia with subcutaneous EPO for 4 months (group A, 26 patients) using saline as the placebo in the control group (group B, 25 patients). We then maintained the EPO treatment in the treated group for another 8 months. Both groups received oral iron throughout the total 12-month period. Echocardiographic evaluation, BNP levels, and hematological parameters are reported at 4 and 12 months.. The patients in group A during the double-blind phase (4 months) demonstrated an increase in LVEF and mild reduction in LVSD and LVSV with respect to baseline and to group B with no differences in PAP, LVDD, and LVDV. Over the 12-month period, the hemoglobin increased from 10.40.6 to 12.4 +/- 0.8 g/dL (P < .01) in group A but did not change in group B. Compared with group B, group A had lower LVDD, LVSD, LVDV, LVSV, LV mass, PAP, and BNP and higher LVEF. The serum creatinine and creatinine clearance remained unchanged in the 2 groups.. In anemic patients with CHF, correction of anemia with EPO and oral iron over 1 year lead to an improvement in LV systolic function, LV remodeling, BNP levels, and PAP compared with a control group in which only oral iron was used.

Topics: Aged; Anemia; Creatinine; Double-Blind Method; Erythropoietin; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Recombinant Proteins; Stroke Volume; Syndrome; Ventricular Remodeling

Topics: Erythropoietin; Female; Humans; Polycythemia; Syndrome; Uterine Neoplasms

We report the case of a 50-year-old woman with severe erythrocytosis and uterine leiomyoma. The suspicion of myomatous erythrocytosis syndrome was supported by erythropoietin level higher than expected. After the supravaginal hysterectomy, the patient's red cell parameters normalized and the erythropoietin level markedly decreased. The authors are discussing the physiology of uterine erythropoietin, the evaluation and differential diagnostic value of erythropoietin investigations. Orv Hetil. 2022; 163(52): 2088-2092.. A szerzők egy 50 éves myomás nőbeteget erythrocytosisa miatt vizsgáltak. A két lelet kapcsolatát, a myomás erythrocytosis gyanúját a vártnál magasabb erythropoetinszint erősítette, majd a supravaginalis hysterectomia a diagnózist igazolta. A műtét után a beteg vérképe normalizálódott, és szérum-erythropoetinszintje jelentősen csökkent. Az eset kapcsán a szerzők az uterusban termelődő erythropoetin fiziológiájáról, a szérum-erythropoetinszintek értékeléséről és differenciáldiagnosztikai hasznáról írnak. Orv Hetil. 2022; 163(52): 2088–2092.

Topics: Erythropoietin; Female; Humans; Hysterectomy; Leiomyoma; Middle Aged; Polycythemia; Syndrome; Uterine Neoplasms

The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and erythrocytosis; (3) monoclonal gammopathy; (4) perinephric fluid collections; and (5) intrapulmonary shunting. Complete resolution of symptoms following treatment with plasma cell-directed therapy supports the hypothesis that the monoclonal antibody is causal and pathogenic. Understanding the basis of the TEMPI syndrome will depend on the identification of additional patients and a coordinated international effort.

Topics: Erythropoietin; Humans; Lung Diseases; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis

Hyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism.. We present the case of a 58-year-old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR).. The patient was ABO group B and had a previously identified anti-Fy(b) alloantibody. After transfusion of Fy(b)--RBCs, she developed a DHTR and was found to have anti-E, anti-C(w), anti-s, and an additional antibody to an unrecognized high-frequency RBC alloantigen. Subsequent transfusion of ABO-compatible RBCs that were negative for Fy(b), E, C(w), and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high-frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. The Hct and clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without a Hb disorder, the development of an antibody to an unknown RBC antigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion.. Hyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due to RBC alloantibodies remains uncertain.

Topics: Acute Disease; Adrenal Cortex Hormones; Anemia, Hemolytic; Antibodies, Monoclonal, Humanized; Blood Group Incompatibility; Cholecystitis; Coombs Test; Drug Resistance; Duffy Blood-Group System; Dyspnea; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Hepatitis C, Chronic; HIV Infections; Humans; Isoantibodies; Middle Aged; Oxygen Inhalation Therapy; Premedication; Pulmonary Disease, Chronic Obstructive; Receptors, Cell Surface; Syndrome; Transfusion Reaction

Collection of hematopoietic progenitor cells by apheresis (HPC-A) requires separation of cells by density. Previous studies highlighted the challenges of HPC-A collection from patients with abnormal red blood cells (RBCs). TEMPI syndrome is a recently described condition defined by teleangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Patients with TEMPI syndrome have responded to therapies used to treat plasma cell dyscrasias and may benefit from autologous HPC transplantation. We report HPC-A collection from a patient with TEMPI syndrome that was complicated by severe iron deficiency.. The patient received granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HPC mobilization and underwent 3 days of HPC-A collection.. The patient presented for collection with a microcytic erythrocytosis. Over 3 days, approximately 50 L of whole blood was processed, and 2 × 10(8) CD34+ cells were collected (2.8 × 10(6) CD34+ cells/kg). The mean collection efficiency (CE), percentage of mononuclear cells, hematocrit (Hct), and RBC count were 18%, 90%, 14%, and 9 × 10(11) , respectively. Altering collection variables to avoid RBC contamination reduced CE. Ficoll preparations of the products after freeze-thaw showed RBC contamination and hemolysis. Postthaw viability exceeded 95%. The products were not RBC reduced or washed. There were no adverse reactions during or after infusion.. HPC-A collection from a patient with TEMPI syndrome was complicated by microcytic erythrocytosis, leading to RBC contamination and hemolysis in the product. Adequate HPCs were collected and the patient tolerated infusion without RBC depletion or washing. Our report highlights difficulties of HPC-A collection from iron-deficient patients.

Topics: Benzylamines; Cyclams; Cytapheresis; Erythrocytes, Abnormal; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Kidney Diseases; Leukocyte Count; Male; Middle Aged; Paraproteinemias; Polycythemia; Syndrome

Recently, a new syndrome of paraganglioma, somatostatinoma, and polycythemia has been discovered (known as Pacak-Zhuang syndrome). This new syndrome, with somatic HIF2A gain-of-function mutations, has never been reported in male patients. We describe a male patient with Pacak-Zhuang syndrome who carries a newly discovered HIF2A mutation. Congenital polycythemias have diverse etiologies, including germline mutations in the oxygen-sensing pathway. These include von Hippel-Lindau (Chuvash polycythemia), prolyl hydroxylase domain-containing protein-2, and hypoxia-inducible factor-2α (HIF-2α). Somatic gain-of-function mutations in the gene encoding HIF-2α were reported in patients with paraganglioma and polycythemia and have been found exclusively in female patients. Through sequencing of the HIF2A using DNA from paraganglioma in 15-year-old male patient, we identified a novel mutation of HIF2A: a heterozygous C to A substitution at base 1589 in exon 12 of HIF2A. The mutation was not found in germline DNA from leukocytes. The C1589A mutations resulted in substitution of alanine 530 in the HIF-2α protein with glutamic acid. This mutation is undoubtedly associated with increased HIF-2α activity and increased protein half-life, because it affects the vicinity of the prolyl hydroxylase target residue, proline 531. To our knowledge, this is the first report describing Pacak-Zhuang syndrome with somatic gain-of-function mutation in HIF2A in a male patient. Congenital polycythemia of unknown origin should raise suspicion for the novel disorder Pacak-Zhuang syndrome, even in male patients.

Topics: Abdominal Neoplasms; Adolescent; Basic Helix-Loop-Helix Transcription Factors; Diagnosis, Differential; Diagnostic Imaging; Erythrocyte Count; Erythropoietin; Follow-Up Studies; Genetic Carrier Screening; Hemoglobinometry; Humans; Male; Neoplasms, Multiple Primary; Norepinephrine; Paraganglioma; Polycythemia; Syndrome

Topics: Adrenal Cortex Hormones; Aged, 80 and over; Darbepoetin alfa; Erythropoietin; Hematinics; Hemolysis; Humans; Lymphoma, Mantle-Cell; Male; Syndrome; Transfusion Reaction

Topics: Antineoplastic Agents; Boronic Acids; Bortezomib; Erythropoietin; Female; Humans; Lymphangiectasis; Middle Aged; Paraproteinemias; Polycythemia; Pyrazines; Syndrome; Telangiectasis

Topics: Antineoplastic Agents; Boronic Acids; Bortezomib; Erythropoietin; Female; Humans; Male; Middle Aged; Paraproteinemias; Polycythemia; Pyrazines; Syndrome; Telangiectasis

This study aimed to explore the relationship between recombinant human erythropoietin (EPO) responsiveness, insulin resistance, and malnutrition-inflammation-atherosclerosis (MIA) syndrome in hemodialysis patients.. This was an observational cohort study in hemodialysis patients. Adipokines, inflammatory cytokines, and required EPO dosage were measured in diabetes (DM; n=58) and non-diabetes (non-DM; n=58) groups over 48 weeks. Furthermore, the EPO responsiveness index (required EPO dosage divided by hemoglobin) was evaluated with or without MIA syndrome in both groups.. The DM group had significantly higher plasma leptin, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP) levels but lower plasma high molecular weight (HMW) adiponectin levels compared to the non-DM group. Although hemoglobin levels were not significantly different, required EPO dosage was significantly higher in the DM group than in the non-DM group, particularly in the presence of MIA syndrome. The DM group with MIA syndrome had significantly higher plasma leptin, IL-6, and hs-CRP levels but lower plasma HMW adiponectin levels compared to the non-DM group with MIA syndrome. There was also a significant association between EPO dosage and homeostasis model assessment for insulin resistance (HOMA-IR), hs-CRP, IL-6, tumor necrosis factor a, leptin, and HMW adiponectin levels in DM patients with MIA syndrome.. Diabetic hemodialysis patients with MIA syndrome have a lower response to EPO and a higher resistance to insulin. This fact may explain the poor outcome of these patients and demonstrate the importance of diagnosis and therapeutic management.

Topics: Aged; Analysis of Variance; Anemia; Atherosclerosis; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Erythropoietin; Female; Glycated Hemoglobin; Hematinics; Humans; Inflammation; Inflammation Mediators; Insulin Resistance; Japan; Kidney Failure, Chronic; Lipids; Male; Malnutrition; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Syndrome; Time Factors; Treatment Outcome

Topics: Adult; Boronic Acids; Bortezomib; Erythropoietin; Female; Humans; Hydronephrosis; Lymphangiectasis; Male; Middle Aged; Paraproteinemias; Polycythemia; Protease Inhibitors; Pyrazines; Syndrome; Telangiectasis

The combination of chronic kidney disease (CKD), chronic heart failure (HF), and anaemia, the so-called cardio-renal-anaemia syndrome (CRA) is associated with dysregulation of erythropoietin levels and inflammation. Both have been associated with the development of cancer. This study aimed to determine the cumulative incidence of cancer in patients with CRA, as compared with anaemic CKD and control patients.. Patients aged <80 years who attended the nephrology or cardiology outpatient clinics between March 2006 and November 2007 were eligible for inclusion in this retrospective case-control study if haemoglobin <8.1 mmol/L (13 g/dL) and serum creatinine >80 mmol/L (0.90 mg/dL). Medical records dating back to 1996 were reviewed. The relationship between cancer and CRA, chronic HF, CKD, and anaemia was analysed using logistic regression analysis. Data from 1087 patients were reviewed. We identified 348 patients with both CKD and anaemia, of whom 132(38.3%) had CRA. The control group included 264 patients attending the hypertension outpatient clinic. Patients with CRA had a 19% cumulative incidence of cancer compared with 11% for patients with anaemia, CKD and no chronic HF, and 11% in the control group. The odds ratio (OR) for cancer was 1.8(95% CI 1.0-3.2) for the CRA group compared with the control group. Chronic HF was an independent risk factor for cancer after correction for age and gender (adjusted OR 2.0; 95% CI 1.2-3.3, P = 0.007).. The cumulative incidence of cancer among patients with CRA is high compared with controls and to anaemic CKD patients without chronic HF. Chronic HF was an independent risk factor for cancer. These results stress the importance of clarifying the mechanisms involved in the development of cancer in CRA.

Topics: Aged; Anemia; Case-Control Studies; Confidence Intervals; Erythropoietin; Female; Heart Failure; Humans; Incidence; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Neoplasms; Netherlands; Odds Ratio; Receptors, Erythropoietin; Retrospective Studies; Risk Factors; Syndrome

The prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce.. To assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 +/- 8 years, left ventricular ejection fraction was 34.5 +/- 14.1, Hb was 10.9 +/- 0.9 g/dL, creatinine was 1.5 +/- 0.5 mg/dL, NT-proBNP was 4256 +/- 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 +/- 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 +/- 1.5 vs. 11.3 +/- 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 +/- 0.8 vs. 8.0 +/- 1.3, P = .016), better NYHA functional class (2.0 +/- 0.6 vs. 3.3 +/- 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001).. Long-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Cohort Studies; Drug Evaluation; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Heart Failure; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Neurotransmitter Agents; Pilot Projects; Prospective Studies; Recombinant Proteins; Survival Rate; Syndrome; Time Factors; Treatment Outcome

Topics: Anemia; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Myocardial Contraction; Natriuretic Peptide, Brain; Recombinant Proteins; Stroke Volume; Syndrome; Systole; Ventricular Function, Left; Ventricular Remodeling

Topics: Anemia; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Prognosis; Syndrome

Incidents of heart and renal failure (HF, RF) together, are increasing in our country and all over the world, so a great attention has been dedicated to this problem recently. These diseases together have shown bad results because of the process of accelerated arteriosclerosis, structural changes of myocardium, oxidative stress, inflammation, increased activities of sympathetic nervous system (SNS), increased activities of a renin-angiotensin-aldosterone system (RAAS) (1). These factors are crucial in the development of patho-physiological process and consequential development of anemia, that together with heart and renal failure through interaction, cause serious disorder that we call the cardio-renal anemia syndrome (2). We examined effects of erythropoietin (Epoetin beta) at 90 (60 men and 30 women) pre-dialysed and dialysed patients with HF signs during a period of three years in individual dozes of 2000-6000 units subcutaneous (sc) weekly. Using computer S PLUS and SAS multiple variant analysis we have got correlations by Pearson. Epoetin beta significantly develops anemia parameters: number of erythrocytes (r=0.51779; p<0.0001), hemoglobin (r=0.38811; p<0.0002), MCV (r=0.59876; p<0.0001) at patients with HF. Positive effects are seen at NYHA class (r=0.59906; p<0.0001), on quality of life before and after prescribing medicine. Parameters of renal functions are improving: more urea (r =0.45557; p<0.0001) than creatinine (r=0.26397; p<0.00119) and potassium values K(+)) are not changed significantly (r=0.02060; p<0.8471). Epoetin beta has been useful in treatment of pre-dialysed and dialysed patients with HF and anemia by improving functional ability of myocardium and quality of life.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Glucose; Blood Urea Nitrogen; Creatinine; Cytokinins; Erythrocyte Count; Erythropoietin; Female; Heart Diseases; Hematopoiesis; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Malnutrition; Middle Aged; Potassium; Recombinant Proteins; Renal Dialysis; Syndrome; Tumor Necrosis Factor-alpha

Topics: Drug Hypersensitivity; Eosinophilia; Epoetin Alfa; Erythema Multiforme; Erythropoietin; Exanthema; Fever; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Syndrome

Topics: Acute Disease; Coronary Artery Disease; Erythropoietin; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Myocardial Infarction; Myocardial Ischemia; Syndrome

Topics: Anemia; Erythropoietin; Fatigue; Humans; Neoplasms; Nursing Assessment; Nursing Diagnosis; Recombinant Proteins; Syndrome

Topics: Adult; Circadian Rhythm; Erythropoietin; Humans; Hypercapnia; Hyperoxia; Hypoventilation; Hypoxia; Male; Middle Aged; Sleep Apnea, Obstructive; Syndrome

Elements of malnutrition-inflammation complex syndrome (MICS) may blunt the responsiveness of anemia of end-stage renal disease (ESRD) to recombinant human erythropoietin (EPO).. The authors examined cross-sectional associations between the required dose of EPO within a 13-week interval as prescribed by practicing nephrologists who were blind to the study and several laboratory values known to be related to nutrition and/or inflammation, as well as the malnutrition-inflammation score (MIS), which is a fully quantitative assessment tool based on the subjective global assessment of nutrition.. A total of 339 maintenance hemodialysis (MHD) outpatients, including 181 men, who were aged 54.7 +/- 14.5 years (mean +/- SD), who had undergone dialysis for 36.3 +/- 33.2 months, were selected randomly from 7 DaVita dialysis units in Los Angeles South/East Bay area. The average weekly dose of administered recombinant human EPO within a 13-week interval was 217 +/- 187 U/kg. Patients were receiving intravenous iron supplementation (iron gluconate or dextran) averaging 39.5 +/- 47.5 mg/wk. The MIS and serum concentrations of high-sensitivity C-reactive protein, interleukin 6 (IL-6), tumor necrosis factor-alpha, and lactate dehydrogenase had positive correlation with required EPO dose and EPO responsiveness index (EPO divided by hemoglobin), whereas serum total iron binding capacity (TIBC), prealbumin and total cholesterol, as well as blood lymphocyte count had statistically significant but negative correlations with indices of refractory anemia. Most correlations remained significant even after multivariate adjustment for case-mix and anemia factors and other relevant covariates. Similar associations were noticed across EPO per body weight tertiles via analysis of variance and after estimating odds ratio for higher versus lower tertile via logistic regression after same case-mix adjustment.. The existence of elements of MICS as indicated by a high MIS and increased levels of proinflammatory cytokines such as IL-6 as well as decreased nutritional values such as low serum concentrations of total cholesterol, prealbumin, and TIBC correlates with EPO hyporesponsiveness in MHD patients.

Topics: Aged; Anemia; Biomarkers; C-Reactive Protein; Epidemiologic Methods; Erythropoietin; Female; Ferric Compounds; Humans; Inflammation; Interleukin-6; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Male; Malnutrition; Middle Aged; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Sex Factors; Syndrome; Tumor Necrosis Factor-alpha

Chronic hepatitis C virus (HCV) infection is quite prevalent in long-term hemodialysis (HD) patients. Patients who are candidates for renal transplantation might be treated, before grafting, with interferon-alpha (IFN-alpha). Among 39 HCV-positive long-term HD patients treated with IFN-alpha, we observed three cases of reversible posterior leukoencephalopathy syndrome (PLES). PLES included headaches in three patients, confusion in three patients, cortical blindness in two patients, visual hallucinations in one patient, seizures in three patients, and respiratory distress in one patient in a context of fluid overload and severe hypertension in all cases. The three patients were receiving IFN-alpha and recombinant erythropoietin therapies simultaneously for de novo anemia. Contrast-enhanced computed tomography scan or magnetic resonance imaging showed low-density areas in the occipital lobes (in three patients), frontal lobes (in one patient), and temporal lobes (in one patient). After withdrawal of IFN-alpha and recombinant erythropoietin therapies, hemodiafiltration, and symptomatic treatment of seizures and hypertension, PLES was reversible within 1 week in one patient, 10 days in one patient, and 2 months in the third patient. Our case reports show the occurrence of reversible PLES in HCV-positive long-term HD patients treated with IFN-alpha. Physicians caring for HCV-positive long-term HD patients treated with IFN-alpha need to be particularly cautious when these patients receive simultaneously recombinant erythropoietin and when IFN-alpha therapy induces a weight loss, which indicates a reduction in dry weight.

Topics: Adult; Anemia; Brain Diseases; Comorbidity; Erythropoietin; Hepatitis C; Humans; Hypertension; Interleukin-1; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Syndrome

Topics: Erythropoietin; Female; Humans; Middle Aged; Platelet Count; Radius; Recombinant Proteins; Syndrome; Thrombocytopenia

To better understand how humans adapt to hypoxia, the levels of hemoglobin (Hb), serum erythropoietin (Epo), and vascular endothelial growth factor (VEGF) were measured in 106 patients with severe obstructive sleep apnea-hypopnea syndrome. The results indicated that temporal hypoxic stimulation increases Hb. Furthermore, a minor increase in Epo and a substantial increase in VEGF were found. The induction in patients with severe sleep apnea was greater than that reported in other types of hypoxia. (Blood. 2001;98:1255-1257)

Topics: Case-Control Studies; Endothelial Growth Factors; Erythropoietin; Hemoglobins; Humans; Hypoxia; Lymphokines; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Syndrome; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC.

Topics: Adult; Anemia, Aplastic; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Hyperpigmentation; Male; Nail Diseases; Syndrome; X Chromosome

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Cranial Nerve Diseases; Erythropoietin; Hemosiderosis; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Myocarditis; Polyneuropathies; Prednisolone; Syndrome

Cisplatin-based therapy results in a cumulative anemia that is disproportionate to the effects on other blood cells. The severity of this treatment-induced anemia and the resultant transfusion requirement in cancer patients correlate with cisplatin-induced renal tubular dysfunction. Observed/expected serum erythropoietin (EPO) ratios decline with progressive cisplatin therapy and are proportionate to the degree of renal dysfunction. Recovery from anemia and of observed/expected serum EPO ratios in patients occurs after cessation of cisplatin therapy, along with restoration of renal tubular function. Creatinine clearance, however, remains permanently depressed. Cisplatin-treated rats develop progressive renal dysfunction and anemia that persists for many weeks, without effects on white blood cell counts. The anemia is also associated with a lack of expected EPO and reticulocyte response. With EPO administration, cisplatin-treated rats exhibit a greater reticulocyte response and hematocrit increment then non-cisplatin-treated rats given EPO, indicating minimal erythroid precursor cell damage from cisplatin. These results indicate the primary etiology of cisplatin-associated anemia is a transient, but persisting EPO deficiency state resulting from cisplatin-induced renal tubular damage, which can be prevented or treated by hormone (EPO) replacement.

Topics: Aged; Aged, 80 and over; Anemia; Animals; Blood Cell Count; Bone Marrow; Cisplatin; Creatinine; Doxorubicin; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Kidney Function Tests; Kidney Tubules; Magnesium; Male; Middle Aged; Multivariate Analysis; Ovarian Neoplasms; Phenylhydrazines; Rats; Syndrome; Urinary Bladder Neoplasms

Topics: Erythropoietin; Gout; Humans; Male; Middle Aged; Pain; Syndrome; Toes; Vasculitis

Topics: Anemia; Erythropoietin; Hematopoietic Stem Cells; Humans; Infant; Male; Syndrome

Topics: Autoantibodies; Blood Viscosity; Castleman Disease; Child; Erythropoietin; Humans; Male; Syndrome

To study the action of corticosteroids on erythroid precursors, (burst forming unit-erythroid and colony forming unit-erythroid) in Diamond-Blackfan Syndrome (DBS), marrow from a newly diagnosed untreated infant was studied in vitro with prednisone and dexamethasone. This patient subsequently proved to be steroid responsive. Colony numbers increased linearly in an erythropoietin (EPO) dose response study. There was marked enhancement of colony numbers at all EPO doses after adding either prednisone (10(-6) M) or dexamethasone (10(-9) M) to the cultures. The data indicate that corticosteroids augment erythropoiesis at both early (BFU-E) and late (CFU-E) stages of development in DBS. In contrast, marrow from a second infant with DBS, clinically steroid resistant, failed to respond to steroids in vitro.

Topics: Anemia, Aplastic; Colony-Forming Units Assay; Dexamethasone; Dose-Response Relationship, Drug; Drug Resistance; Erythropoiesis; Erythropoietin; Humans; In Vitro Techniques; Infant; Infant, Newborn; Prednisone; Syndrome

The development since 1966 of a technology for growing stem cells in vitro has provided new insights into the controls of blood cell production. Hematopoietic hormones have been purified and important cellular interactions in hematopoiesis have been defined.

Topics: Anemia, Aplastic; Cell Communication; Erythrocytes, Abnormal; Erythropoietin; Forecasting; Granulocytes; Growth; Hematopoiesis; Hematopoietic Stem Cells; Leukemia, Myeloid, Acute; Models, Biological; Polycythemia; Preleukemia; Syndrome; Technology

The profound anemia of Diamond-Blackfan syndrome (DBS) is due to marrow red cell failure, but the pathogenesis is not understood. Studies by others indicated cell-mediated erythropoietic suppression in this condition. To explore this mechanism further, Ficoll-Hypaque--separated peripheral blood lymphocytes (PBL) from four anemic untreated patients with DBS, or from normals were cocultured with control marrow in vitro and the growth of erythropoietin-responsive stem cell colonies (CFU-E) was dermined. CFU-E numbers obtained from cultures with added normal PBL were not significantly different from the number without PBL. Similarly, CFU-E from cultures with added DBS PBL were not significantly different from the number without PBL (215 versus 220, 229 versus 220 and 84 versus 60, 74 versus 94/10(5) cells, respectively). Mixing marrows from a control and one DBS patient in ratios of 2:1, 1:1, or 1:2 prior to culture failed to disclose a decrease of colony growth. We could not show cellular inhibition of erythropoiesis in these patients with DBS. The mechanism of anemia in this disorder remains an open question.

Topics: Bone Marrow Cells; Cells, Cultured; Child, Preschool; Erythrocytes, Abnormal; Erythropoietin; Female; Humans; Immunity, Cellular; Immunosuppression Therapy; Infant; Male; Syndrome

A summary of the historical developments associated with congenital anemias are discussed. The clinical status, the peripheral blood and bone marrow picture of these patients are reviewed. The effectiveness of treatment and prognosis for these patients is evaluated.

Topics: Adrenal Cortex Hormones; Adult; Anemia; Anemia, Aplastic; Blood Transfusion; Bone Marrow; Erythropoietin; Hemosiderosis; Humans; Syndrome

The results of the erytropoietin level determination in serum and urine of patients with congenital anemias are presented and compared to the results obtained in children with acute aplastic anemias. Three patients with congenital hypoplastic anemia Diamond-Blackfan, two with Fanconi's anemia, one with congenital pancythopenia with hyperplastic marrow and five patients with acute aplastic anemia were studied. The increased serum erythropoietin level was found in every patient whose blood hemoglobin was less than 12g%. Erythropoietin was detected in nonconcentrated urine when serum erythropoietin level was higher than 0,5 units/ml. The statistically significant negative correlation between the serum erythropoietin level and blood hemoglobin concentration was found. In two patients suffering from congenital anemias, in whome the significantly increased erythropoietin level (about 1.0 units/ml) was detected, increased ammount of hemoglobin F in peripheral blood as well as increased MCV--signs of so called "stress" erythropoiesis-were noted. The results presented, together with the results obtained by other authors, indicate that congenital anemias studied here are not due to the disturbance in erythropoietin production.

Topics: Adolescent; Adult; Anemia, Aplastic; Child; Child, Preschool; Erythrocytes, Abnormal; Erythropoietin; Fanconi Anemia; Female; Humans; Infant; Male; Syndrome

Four children with congenital hypoplastic anemia (Diamond-Blackfan syndrome) and 30 control children with normal erythropoiesis were studied by a cell culture method in which human marrow, grown in a plasma clot, responds to added erythropoietin (EPO) with the appearance of discrete colonies of nucleated erythroid cells. The colonies arise from EPO-responsive stem cells and are not related to the number of morphologically identifiable marrow erythroids plated. Results of studies on control marrow indicated that without EPO there was little or no colony formation. Increasing EPO doses or nucleated marrow cells per culture resulted in a linear increase in colony numbers. The optimal EPO concentration of 2.5 U/ml yielded a mean of 158 +/- 79 colonies/1 x 10(5) nucleated cells on day 7 of incubation. Even in the absence of recognizable erythroids, marrows of all four patients with anemia grew erythroid colonies. Two patients on no therapy had decreased colony numbers. The other two, on prednisone, had normal numbers. Sera from patients did not inhibit colony formation from either autologous or control marrow. In contrast, serum from an adult with acquired pure red cell aplasia produced striking inhibition of colony growth. It appears that the red cell failure in this disorder is not due to an absence of erythroid stem cells, and a serum inhibitor to erythropoiesis as seen in the acquired disease is unlikely.

Topics: Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Child, Preschool; Culture Techniques; Erythrocytes, Abnormal; Erythropoiesis; Erythropoietin; Humans; Infant; Infant, Newborn; Syndrome

The response of bone marrow to erythropoietin (EPO) from five children with the Diamond-Blackfan syndrome, also known as congenital hypoplastic anaemia (CHA), was tested in tissue culture by measurement of haem synthesis. Studies of 13 control marrows indicated that the maximum EPO effect occurred at approximately 70 h incubation using an EPO concentration of 0.2-0.3 units/ml and a nucleated cell concentration of 5 x 10(6) per culture. Under these conditions, haem synthesis was 121% greater in EPO-stimulated than in unstimulated cultures. Patients with CHA with anaemia and diminished marrow erythroids had reduced or absent haem synthesis. In one patient, haem production became normal after a spontaneous remission, and was not inhibited by autologous plasma drawn at the time of diagnosis. Plasma from three patients did not show inhibitory activity when cultured with control marrow. In contrast, plasma from an adult with acquired pure red cell aplasia produced striking inhibition of haem synthesis when cultured with control marrow. We conclude that, in comparison to some cases of the adult acquired condition, CHA is not due to inhibitors or antibodies. When present, erythroid precursors in children with CHA are capable of responding normally to EPO with increased haem synthesis.

Topics: Anemia, Aplastic; Bone Marrow; Child, Preschool; Dose-Response Relationship, Drug; Erythrocytes, Abnormal; Erythropoietin; Female; Heme; Humans; Male; Syndrome

Topics: Anemia, Aplastic; Animals; Antibodies; Autoradiography; Cell Differentiation; Cell Division; Cells, Cultured; Centrifugation; Dialysis; DNA; Erythrocytes, Abnormal; Erythropoiesis; Erythropoietin; Hematopoietic Stem Cells; Humans; Microscopy, Electron; Rabbits; Staining and Labeling; Stimulation, Chemical; Syndrome; Thymidine; Tritium