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We describe presenting features, treatment strategies, and follow-up events involving 41 patients (median age 39 years, range 1-81; 54% males) with high oxygen affinity (HOA) hemoglobinopathy-associated erythrocytosis, seen at our institution (1973-2020). Thirty-four (83%) patients carried β-chain (13 Malmo, 4 Olympia, 3 San Diego, 2 Wood) and 7 (17%) α-chain (4 Dallas and one each Columbia-Missouri, Jackson, and Wayne) variants. Median (range) hemoglobin (Hgb)/hematocrit (Hct), serum erythropoietin and p50 were 18 g/dL/52.9% (16-21.9/48-66), 10.4 mIU (4-36.3), and 20 mmHg (12-25), respectively. Family history was documented in 24 patients and history of thrombosis in two (5%). Treatment included phlebotomy in 23 and antiplatelet therapy in 21 patients. At a median follow-up of 10 years, 23 (56%) patients reported one or more symptoms that were thought to be related to their increased Hct while thrombosis was documented in 10 (24%) patients. Neither Hgb/Hct level nor active phlebotomy showed a significant correlation with either thrombotic or nonthrombotic symptoms (p > .1 in all instances). Among 23 pregnancies recorded, 78% resulted in live births and no fetal loss was attributed to erythrocytosis. The current study does not implicate Hgb/Hct level as a major contributor of morbidity in HOA hemoglobinopathy-associated erythrocytosis and suggests limited therapeutic value for phlebotomy.

Few minutes of hypoxic exposure stabilizes hypoxia-inducible factor-1α, resulting in erythropoietin (EPO) gene transcription and production. The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum EPO levels in healthy individuals. In a first experiment, spontaneous EPO changes under normoxia (NORM) and the EPO response to five 4-min cycles of intermittent hypoxia (IH5) were determined in six individuals. In a second experiment, the EPO response to eight 4-min cycles of intermittent hypoxia (IH8) and 120 min of continuous hypoxia (CONT) was determined in six individuals. All hypoxic protocols were performed at a targeted arterial oxygen saturation of 80%. There was no significant change in EPO levels in response to normoxia or in response to five cycles of intermittent hypoxia (NORM: 9.5 ± 1.8 to 10.5 ± 1.8, IH5: 11.4 ± 2.3 to 13.4 ± 2.1 mU/mL, main effect for time

Background Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis. Objective To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs. Animals Forty-seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls. Methods Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO2] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis. Results Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0-17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13-38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0-14) dogs. No marked polycythemia (Hct >= 65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO2: Erytr, r = -.14; Hb, r = -.21; Hct, r = -.14; P > .05 for all). Conclusions and Clinical Importance Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.

Summary Objectives Reference values of hematologic parameters are imperative not only in clinical applications but also for monitoring of banned substances in sports. Since the values can be highly influenced by sexes, genetic origins and geographical factors, we assessed the haematological parameters of junior athletes from the Malaysian population. This study aimed to establish local haematological reference values of athletes and to compare the variation of these values between several sub-populations. Methods Complete blood count and erythropoietin level quantification were performed on a total of 126 subjects from 3 major ethnic groups to measure 11 haematology parameters. Independent Sample T-Test and Analysis of Variance were done in order to access the variation between several sub-populations. Results Results showed that 7 out of 11 haematology parameters were significantly different (P ≤ 0.05) among groups of gender and ethnicity. The variations between genders were seen in the red blood cell, haemoglobin, haematocrit, mean cell haemoglobin corpuscular, platelet and OFF-Score values. The values of mean corpuscular volume and mean cell haemoglobin corpuscular were found to be significantly different between ethnic groups. We also found that our haematological reference ranges for junior athletes fall within the previously established local population ranges. Conclusions The hematologic parameters have been proven to be highly influenced by sex and ethnicity of athletes. In this work, we managed to establish the reference ranges of hematologic parameters among Malaysian junior athletes. The data also included the values for reticulocytes, OFF-Score and serum erythropoietin that have never been reported before for the local population.

Renal impairment (RI) is a common clinical presentation in patients with multiple myeloma (MM). Despite treatment with novel agents or management strategies that focus on the disease response, some patients develop irreversible RI. This study aimed to determine the influencing, clinical variables of renal reversibility in patients with RI treated with novel drugs. We analyzed 244 patients newly diagnosed with MM retrospectively. Maximum renal response was assessed according to the criteria for the definition of renal response proposed by the International Myeloma Working Group. Major renal response was defined as the occurrence of complete renal response or partial renal response. RI (a glomerular filtration rate 25 mIU/mL (P 25 mIU/mL and urinary albumin ≤25%. The estimated 6‐month rates of major renal responses of patients with scores of 2, 1, and 0 were 78.6%, 30.6%, and 0%, respectively (P 25 mIU/mL is an independent predictive factor for major renal response and may predict renal reversibility more accurately when urinary albumin level is congruently ≤25%., Renal impairment (RI) is a common complication of multiple myeloma (MM), and this study aimed to determine the influencing, clinical variables of renal recovery in RI patients treated with novel drugs. Serum erythropoietin (EPO) levels >25 mIU/mL and percentage of urinary albumin ≤25%, were both significantly associated with a shorter time to major renal response. Serum EPO level >25 mIU/mL is an independent positive predictive factor for major renal response and predict renal reversibility more accurately when urinary albumin level is congruently ≤25%.

Introduction. Drinking water is a necessary element of life support of the population. Many studies conducted around the world have established a relationship between the quality of drinking water and public health. On the basis of the Perm State Medical University studies were conducted to assess the effects of oxygen-enriched drinking water on human respiratory, cardiovascular and nervous systems as well as serum erythropoietin (EPO) levels. The objects of study were 32 volunteers (7 men and 25 women) aged 18 to 28. The purpose of the research was to study the effect of oxygen-enriched drinking water on the basic physiological systems of the human body and serum EPO levels of healthy volunteers. Methods. We applied the following research methods: physiological methods were used thrice (on the first, tenth and twenty-first days) to test the cardiovascular (heart rate, SBP, DBP, Kerdo index, Harvard step test), respiratory (BH, JELL, JEL, Stange and Gencha tests) and nervous (Anfimov test, SAN test, ShAS test) systems; laboratory tests of serum EPO levels in venous blood of the volunteers; and statistical methods (statistical processing was performed using Microsoft Office Excel 2007 and STATISTICA V. 7 software package (StatSoft Inc., USA). Results. The use of oxygenated water helps increase functional and reserve capabilities of the basic physiological systems of the body and improve tissue oxygenation.

Purpose Serum erythropoietin (EPO) concentration is increased following static apnoea-induced hypoxia. However, the acute erythropoietic responses to a series of dynamic apnoeas in non-divers (ND) or elite breath-hold divers (EBHD) are unknown. Methods Participants were stratified into EBHD (n = 8), ND (n = 10) and control (n = 8) groups. On two separate occasions, EBHD and ND performed a series of five maximal dynamic apnoeas (DYN) or two sets of five maximal static apnoeas (STA). Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on EPO. Peripheral oxygen saturation (SpO2) levels were monitored up to 30 s post each maximal effort. Blood samples were collected at 30, 90, and 180 min after each protocol for EPO, haemoglobin and haematocrit concentrations. Results No between group differences were observed at baseline (p > 0.05). For EBHD and ND, mean end-apnoea SpO2 was lower in DYN (EBHD, 62 ± 10%, p = 0.024; ND, 85 ± 6%; p = 0.020) than STA (EBHD, 76 ± 7%; ND, 96 ± 1%) and control (98 ± 1%) protocols. EBHD attained lower end-apnoeic SpO2 during DYN and STA than ND (p p p = 0.622). EBHD EPO increased from baseline (6.85 ± 0.9mlU/mL) by 60% at 30 min (10.82 ± 2.5mlU/mL, p = 0.017) and 63% at 180 min (10.87 ± 2.1mlU/mL, p = 0.024). Serum EPO did not change after the STA (EBHD, p = 0.534; ND, p = 0.850) and STE (p = 0.056) protocols. There was a significant negative correlation (r = − 0.49, p = 0.003) between end-apnoeic SpO2 and peak post-apnoeic serum EPO concentrations. Conclusions The novel findings demonstrate that circulating EPO is only increased after DYN in EBHD. This may relate to the greater hypoxemia achieved by EBHD during the DYN.

The prevalence of anemia increases with advancing age, and despite thorough investigation, approximately one-third will be classified as "unexplained." Unexplained anemia (UA) is typically hypoproliferative, normocytic, and with low reticulocyte count. Serum erythropoietin levels are lower than expected for degree of anemia. Chronic inflammation, low testosterone levels, malnutrition, and possibly nascent myelodysplasia are variably contributing factors. No clearly established beneficial treatment strategy has been established, but the association of UA with a wide range of adverse outcomes, including impaired quality of life, physical function, and mortality, is sufficiently compelling to justify expanding clinical research focused on basic and clinical aspects.

The purpose of this study was to investigate the effect of 6 weeks of oral Echinacea purpurea supplementation on serum erythropoietin (EPO) and erythropoietic status. Twenty-four males (mean ± SE; age = 25.2 ± 1.4 years, height = 178.1 ± 1.4 cm, body mass = 78.1 ± 1.6 kg, body fat = 12.7 ± 0.9%, maximal oxygen uptake = 52.9 ± 0.9 mL·kg−1·min−1) were randomly grouped using a matched-pair, double-blind design and self-administered 8000 mg·day−1 of either E. purpurea (n = 12) or placebo (n = 12) for 42 consecutive days. Blood samples were collected prior to supplementation (day 0) and every 2 weeks during the supplementation period (days 14, 28, and 42) and were analyzed for EPO, red blood cell count, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Separate 2 × 4 (group × time) factorial ANOVA with repeated measures on time were used to determine statistical differences with significance set at p ≤ 0.05. There were no significant interaction, group, or time effects observed for EPO or erythropoietic status markers for any of the measurement points (p ≤ 0.05). The present study indicated that 6 weeks of oral E. purpurea supplementation in recreationally active males with above average aerobic fitness did not enhance EPO or erythropoietic status. These findings are in contrast with previous reports of E. purpurea supplementation in untrained participants with average fitness levels, but consistent with observations in trained endurance athletes.

We assessed the diagnostic performances of erythropoietin and JAK2 mutations in 1,090 patients with suspected polycythemia who were referred for red cell mass (RCM) measurement. In patients with a high haematocrit and/or haemoglobin level, a low erythropoietin level (=3·3 mUI/ml) and JAK2 mutation showed comparable positive predictive value (PPV) for true polycythemia (RCM=125%), 92·1% and 90% respectively. A very-low erythropoietin level (=1·99 mUI/ml) had a PPV of 100% for polycythemia vera (PV) diagnosis. We confirmed the correlations between RCM, erythropoietin and JAK2 variant allelic frequency in PV patients. This study prompts the need to revisit the role of EPO in PV diagnostic criteria.

Background: We evaluated the frequency of subnormal erythropoietin levels, JAK2V617F positivity and polycythemia vera (PV) in patients who did not meet WHO 2008 criterion for hemoglobin levels but were suggested to be investigated for PV in 2016 revision. Materials and Methods: We assessed the data of 92 patients, who were further evaluated with JAK2V617F mutation and serum erythropoietin (EPO) levels and bone marrow biopsy, if necessary. We also compared this patient group with 20 patients whose Hgb>18.5 g/dL for men and >16.5 g/dL for women. Results: Nine patients (45%) in the higher hemoglobin group were JAK2V617F positive, while 4 patients (4.3%) in the lower hemoglobin group were JAK2V617F positive (p

Primary familial and congenital polycythemia (PFCP) is a rare autosomal dominant disorder caused by hypersensitivity of erythropoietin receptor of erythroid progenitors leading to increased rate of erythropoiesis at any given serum erythropoietin level. The hallmark of this disorder is isolated erythrocytosis with the absence of splenomegaly and lack of secondary causes of polycythemia. In this short review, we will shed light on various aspects of PFCP with special focus on molecular pathogenesis and diagnostic approach.

Background Approximately 100 high oxygen affinity (HOA) hemoglobin (Hgb) variants have been reported to date; review of the Mayo Clinic laboratory database (1974-2018) identified 80 distinct variants including 12 novel variants (60 β, 20 α). One-third of HOA Hgb variants result in secondary erythrocytosis, provoking concern regarding increased risk for thrombosis. Current management guidelines lack supporting evidence regarding the utilization of phlebotomy in such cases. We describe presenting features, treatment strategies and follow-up events involving 41 consecutive cases seen at our institution. Methods Study patients were recruited from our institutional laboratory and clinical Hgb variant database. Initial evaluation for Hgb variants was conducted by capillary electrophoresis and high-performance liquid chromatography. Additional testing which included mass spectrometry and isoelectric focusing was pursued as necessary. Since the majority of variants were difficult to identify by protein studies, DNA sequencing of HBB, or HBA1, HBA2 genes was performed for confirmation. Symptoms and thrombosis, both at presentation and during follow up, were recorded. Therapeutic interventions were based on physician discretion and mostly included phlebotomy and/or aspirin therapy; a careful response assessment was performed to determine the impact of each therapy on symptoms and/or thrombosis. Results A total of 41 patients with HOA Hgb variant-associated erythrocytosis (median age 39 years, range 1-81; 54% males) were seen at our institution between January 1973 and February 2020. The majority of the patients carried β-chain variants (n=34; 83%), common variants being Hgb Malmo (n=13), Olympia (n=4), San Diego (n=3), and Wood (n=2). Among the 7 patients with α-chain variants, Hgb Dallas was the most frequent (n=4). Presenting median values (range) for Hgb/Hct, serum erythropoietin and p50 were 18 g/dl/52.9%(16-21.9g/dl/48-66%) 10.4 mIU (4-36.3 mIU), and 20 mmHg (12-25 mmHg), respectively. Family history was documented in 34 patients, of which 24 (71%) reported one or more affected family members. Family history of thrombosis was documented in 7 patients (21%). CV risk factors were present in half of the patients; by contrast, history of thrombosis prior to or at diagnosis was documented in only two patients (5%). Of 23 pregnancies reported in 12 women, live birth rate was 78% (n=18); none of the fetal losses were attributed to erythrocytosis. Active therapies at the time of initial referral consisted of phlebotomy (n=12), aspirin (n=11) and systemic anticoagulation (n=1). At a median follow-up of 10 years (range; 0.04-44), 23 patients had reported one or more symptoms, attributed to hyper-viscosity, such as headaches, fatigue, and lightheadedness. Neither Hct level at diagnosis (p=0.32) nor phlebotomy (p=0.16; 75% patients on vs 52% not on phlebotomy) or aspirin therapy (p=0.75; 55% patients on vs 60% not on aspirin) appeared to influence the occurrence of symptoms. Phlebotomy relieved symptoms in 7 (42%) symptomatic patients; however, 7 (30%) of 23 patients on phlebotomy reported one or more adverse symptoms that were attributed to phlebotomy-induced iron deficiency. Ten patients (24%) experienced thrombosis prior to or following diagnosis: 6 arterial and 4 venous. Median age at thrombotic event was 51 years and median hematocrit 52%; active therapies at the time of event included phlebotomy in 5 patients, aspirin in 4, and systemic anticoagulation in 2. Hct level at diagnosis (p=0.10) or the time of event (p=0.67) did not correlate with occurrence of thrombosis. Additionally, the incidence of thrombosis was no different among patients receiving or not receiving phlebotomy (5/23(22%) vs 5/18(28%), respectively; p=0.66). The presence of CV risk factors was predictive of arterial events (p=0.002). Two of the 4 venous events developed in the context of concomitant thrombophilia. Eight patients (20%), median age 28 years, without CV risk factors, were observed without therapy for a median of 9.5 years (range; 0.4-21) and have not experienced any thrombosis to date. Conclusions We found no association between Hct level and either thrombotic or non-thrombotic symptoms in HOA hemoglobinopathy-associated erythrocytosis; furthermore, implementation of aggressive phlebotomy did not provide a clear benefit with respect to thrombosis risk reduction. Figure 1 Figure 1. Disclosures Patnaik: StemLine: Research Funding; Kura Oncology: Research Funding.

Aim: To evaluate the correlation of iron deficiency anemia with thrombocytosis in correlation with serum erythropoietin levels. Introduction: Thrombocytosis is a common hematologic finding that can present as an incidental finding and can lead to a great diagnostic challenge. Thrombocytosis can be caused due to autonomous or as a reactive overproduction secondary to infections, iron deficiency anemia, malignancies. Erythropoietin (EPO) is the primary regulator of erythrocyte production and also affects thrombopoiesis and platelet function. The mechanism leading to thrombocytosis in cases of iron deficiency anemia (IDA) remains unclear. Hence, this study was undertaken to evaluate correlation between IDA with thrombocytosis and serum EPO levels. Materials & Methods: A total of 50 patients of all the age groups attending out-patient and inpatient departments of Basaveshwara Medical College Hospital and Research center, Chitradurga suspected of having microcytic hypochromic anemia on initial hematological investigations were included for study over a period from January 2016 to august 2016. Relevant investigations like peripheral smear study, serum iron studies and serum erythropoietin levels were subsequently performed. Results: Majority 52% (n=26) had anemia between 7-9.9 gm/dl of which 57.69% (n=15) cases had platelet count between 5-7 lakhs/cu.mm, 34.61% (n=9) cases had moderate thrombocytosis and 7.69% (n=2) cases had severe thrombocytosis. Out of 50 cases in the present study 76% (n=38) cases had significant increase in the levels of serum erythropoietin while 24% (n=12) cases had normal serum erythropoietin. Conclusion: From the present study, it may be concluded that erythropoietin would play a significant role in causing thrombocytosis in patients with iron deficiency anemia.

In the randomized, phase 3, MDS-005 study (NCT01029262), lenalidomide-induced red blood cell transfusion independence (RBC-TI) in 27% of transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS) ineligible for or refractory to erythropoiesis-stimulating agents. To determine the influence of erythropoietin (EPO) level on response, 155 patients treated with lenalidomide in MDS-005 were categorized into four groups by baseline EPO level. The EPO500 mU/mL group had higher RBC transfusion burden and the lowest proportion of patients with ring sideroblasts ≥15% versus lower EPO groups. Achievement of RBC-TI ≥8 weeks inversely correlated with EPO level, ranging from 42.5 to 15.5%. EPO level did not affect erythroid hematologic improvement response (36.2-44.4%). This analysis suggests patients with lower EPO levels experience the strongest benefit from lenalidomide. Although meaningful improvements were observed in some patients with EPO level500 mU/mL, new treatments are needed for this population.

Background Erythropoietin (EPO) is one of the systemic angiogenic factors, and its role in ocular angiogenesis and in diabetic retinopathy (DR) is not yet fully understood. The latest research data reveal a possible correlation of higher erythropoietin concentrations in the blood and in the eye with the development of more advanced stages of DR. The main aim of this work was to examine the possible influence of serum concentrations of erythropoietin on the development of diabetic retinopathy in patients with diabetes mellitus type 2. Methods The research involved 90 patients examined at the University Eye Clinic of the Clinical Center of Vojvodina, Novi Sad, Serbia. The first group comprised 60 patients with diabetes mellitus lasting for 10 years or more, with diabetic retinopathy. The second, control group consisted of 30 healthy individuals. In the first group of 60 patients with diabetes, 30 of them had non-proliferative diabetic retinopathy (NPDR), and 30 had proliferative diabetic retinopathy (PDR). Laboratory EPO serum levels were determined, and they were correlated to the stage of DR. Concentration of EPO was assessed by ELISA method. Results The highest average concentration of EPO in serum (9.95 mIU/ml) was determined in the group of people with diabetes with PDR. The lowest average concentration of EPO in the serum (6.90 mIU/ml) was found in the control group. The average concentration of EPO in serum in the group of patients with diabetes with NPDR was 7.00 mIU/ml. The EPO concentration in serum was elevated in the group of PDR, and it was directly proportional to the level of the clinical stadium of PDR, being significantly higher in the moderate and severe subgroup of PDR comparing to the control healthy subjects, NPDR and mild PDR (p = 0.007). Conclusions Significantly elevated serum concentration of EPO in the advanced stages of DR, and positive correlation between EPO serum concentration and clinical stages of PDR, suggest that erythropoietin represents an important growth factor from blood, which plays a significant role in retinal ischemia and angiogenesis in diabetic retinopathy, especially in the proliferative stage of this disease.

Hemoglobin levels are believed to be regulated as per a set point model of regulation. This model of regulation, by which specific levels of a parameter are targeted and defended by physiological systems, implies a particular population correlation between the parameter and its controlling hormone. Empirical population correlations of other parameters and their controlling hormones, have denied the presence of such set point‐based regulation. To assess if hemoglobin is regulated according to a set point model we performed a systematic search of PubMed/MEDLINE and Web of Science identifying relevant reports published up to November 2018. Population hemoglobin/erythropoietin level correlations were retrieved, and these empirically derived correlations were compared with the positive correlation implied by a set point model of regulation. Authors of papers containing potentially suitable data were contacted with requests for further analyses, and a meta‐analysis was performed. Twelve correlations between hemoglobin and erythropoietin levels from eleven papers were analyzed. None of these correlations were significantly positive, three, restricted to the normal range of hemoglobin, were significantly negative. All but one of the other correlations showed a negative trend. New analyses of previously published data sets resulted in similar findings. In particular a new analysis of large data sets of males (n = 2417) and females (n = 2592) with normal range hemoglobin levels, revealed significantly negative correlations. A meta‐analysis of our results indicated that the data overall are not consistent with a positive relationship between hemoglobin and erythropoietin (P

Objective Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion. Methods A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3). Results There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = −0.210, p = 0.006). Conclusions Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.

Multiple algorithms have been published for the evaluation of hereditary erythrocytosis (HE). Typical entry points begin after excluding the more common acquired conditions through investigations of clinical history and assessment of cardiac, pulmonary, or vascular system disorders. Prior exclusion of JAK2 mutations, particularly the common JAK2 V617F mutation, is indicated in adults but less so in pediatric populations. Key decision trees are based on serum erythropoietin levels and p50 results. Recent data reveal some overlap in clinical presentation and laboratory findings in erythrocytosis. Caveats to consider when using algorithmic approaches are discussed.

Introduction: Diabetes is a disease characterised by poor glycaemic control and development of various complications with age. Diabetic complications include development of nephropathy as well as other complications. Aim: The study was aimed to elucidate the consequences of diabetic nephropathy on erythropoietin levels and microalbuminuria. Materials and Methods: A total of 66 subjects with Type II Diabetes Mellitus (T2DM) with and without microalbuminuria and 22 healthy subjects were enrolled in the present study. The following case-control study was completed in Al-Najaf Centre for Diabetes and Endocrinology, Al-Najaf City, Iraq from March 2016 to May 2016. Serum erythropoietin levels and microalbuminuria concentrations were documented in addition to demographic and biochemical data. Results: Serum erythropoietin concentrations were decreased significantly in patients with T2DM compared to that of healthy control subjects. Microalbuminuria concentrations were increased significantly in patients with T2DM compared to that of healthy control subjects. Conclusion: Microalbuminuria and erythropoietin levels can be used to assess the occurance of complications in patients with diabetic nephropathy.

Introdução: A síndrome mielodisplásica é uma doença heterogénea caracterizada por displasia, medula hipercelular, citopenias e risco de evolução para leucemia aguda. Outros factores de prognóstico, nomeadamente, fibrose medular, elevação da enzima desidrogenase do lactato e β2-microglobulina têm sido descritos, contudo, a decisão terapêutica baseia-se no score do International Prognostic Scoring System.Material e Métodos: Este trabalho teve como objectivo analisar a relevância da eritropoietina sérica ao diagnóstico, em doentes com síndrome mielodisplásica de novo, avaliando o seu impacto na sobrevivência global e a sua implementação como factor de prognóstico. Recolhemos dados clínicos e laboratoriais de 102 doentes com síndrome mielodisplásica de novo diagnosticada entre outubro/2009 e março/2014. A análise de sobrevivência foi efectuada recorrendo à metodologia de Kaplan-Meier, de acordo com os valores de eritropoietina.Resultados: A amostra, de 102 doentes, apresenta uma mediana de idades de 74 anos e relação masculino/feminino igual a 0,8. Os doentes com o subtipo citopenia refratária com displasia unilinha apresentam, em média, valores de eritropoietina significativamente mais baixos, em oposição aos doentes com o subtipo 5q- que apresentam a média de eritropoietina sérica mais elevada (p < 0,05). Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001).Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcutânea, sendo que os doentes com síndrome mielodisplásica com valores mais elevados de eritropoietina apresentam uma pior resposta à administração de eritropoietina, mesmo com doses mais elevadas. A nossa amostra demonstra que a eritropoietina sérica apresenta também valor prognóstico, e em todos os subtipos de síndrome mielodisplásica. Além disso, isoladamente ou em associação com outros factores ou índices de prognóstico, poderá melhorar o valor prognóstico de índices como o International Prognostic Scoring System, uma vez que valores elevados de eritropoietina estão associados a progressão para leucemia aguda e, consequentemente, a menor sobrevivência.Conclusão: Os resultados sugerem que o aumento dos níveis séricos de eritropoietina ao diagnóstico pode constituir um factor de mau prognóstico em doentes com síndrome mielodisplásica, associando-se a maior risco de evolução para leucemia aguda e menor sobrevivência global.

In this work, the effect of fullerenol on erythropoiesis was investigated in healthy rats and in rats that had suffered blood loss in the amount of 2% of body weight. Fullerenol C60(OH)24 was diluted in 2 mL of 0.9% sodium chloride solution and injected intraperitoneally in a dose of 0.1 or 0.2 mg/kg body weight. The counts of reticulocytes, erythrocytes, and serum erythropoietin levels were determined in 48 and 96 h, as were the numbers of erythroid cells and erythroblastic islands (EIs) of different maturity fractions in the bone marrow and the fraction of the red pulp in the spleen. In intact rats, the reconstruction of erythropoiesis was augmented 1.5-fold in response to 0.1 mg/kg fullerenol C60(OH)24 and 3.3-fold in response to 0.2 mg/kg fullerenol. Both doses increased the number of oxyphylic erythroblasts in the bone marrow twofold, and 0.2 mg/kg fullerenol increased the red pulp fraction in the spleen by 9%; at the same time, fullerenol did not affect the counts of reticulocytes and erythrocytes, or the serum erythropoietin level in the case of normal erythropoiesis. Following hemorrhage, exposure to a 0.2 mg/kg dose of fullerenol C60(OH)24 increased serum erythropoietin levels, delayed the maturation of erythroid cells in EIs, partially blocked the release of reticulocytes from the bone marrow, and promoted an increase in the relative spleen weight and the red pulp fraction in the spleen.

Objective: To measure the serum erythropoietin (EPO) level in patients with saphenous vein grafts (SVGs) and to compare the EPO level in those with and without SVG disease. Subjects and Methods: The study included 85 consecutive patients with a history of coronary artery bypass graft surgery that underwent elective coronary angiography. Patients with >30% stenosis (diseased grafts) in at least one saphenous graft were included in group 1 (diseased group: n = 40), and group 2 (nondiseased group: n = 45) consisted of patients without diseased SVGs. The EPO level was measured using enzyme-linked immunosorbent assay (ELISA) using a commercially available ELISA kit; χ2 test and independent samples t test were used where appropriate. Logistic regression was used for multivariate analysis. Results: There were not any significant differences in age, gender, or cardiovascular risk factors between the two groups except for increased triglyceride and low high-density lipoprotein levels in group 2. The EPO level was significantly higher in the nondiseased SVG group than in the diseased SVG group (25.5 ± 9.6 vs. 17.8 ± 6.8 mU ml-1, p = 0.002). Multivariate logistic regression analysis showed that the serum EPO level was an independent predictor of SVG disease (OR 1.14, 95% CI 1.06-1.24, p = 0.001). Conclusion: In this study, SVG disease was associated with a low serum EPO level, suggesting that a low EPO level could be predictive of and contributes to the pathophysiology of SVG disease.

Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum erythropoietin, and erythrocytosis/polycythemia. This phenotype is recapitulated by a mouse model bearing a homozygous VhlR200W mutation. We previously showed that iron-regulatory protein 1-knockout (Irp1-knockout) mice developed erythrocytosis/polycythemia through translational derepression of Hif2α, suggesting that IRP1 could be a therapeutic target to treat Chuvash polycythemia. Here, we fed VhlR200W mice supplemented with Tempol, a small, stable nitroxide molecule and observed that Tempol decreased erythropoietin production, corrected splenomegaly, normalized hematocrit levels, and increased the lifespans of these mice. We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated. Thus, a new approach to the treatment of patients with Chuvash polycythemia may include dietary supplementation of Tempol, which decreased Hif2α expression and markedly reduced life-threatening erythrocytosis/polycythemia in the VhlR200W mice.