Macrophages: key players in erythrocyte turnover

ABSTRACT The development of red blood cells (RBCs), or erythropoiesis, occurs in specialized niches in the bone marrow, called erythroblastic islands, composed of a central macrophage surrounded by erythroblasts at different stages of differentiation. Upon anemia or hypoxemia, erythropoiesis extends to extramedullary sites, mainly spleen and liver, a process known as stress erythropoiesis, leading to the expansion of erythroid progenitors, iron recruitment and increased production of reticulocytes and mature RBCs. Macrophages are key cells in both homeostatic and stress erythropoiesis, providing conditions for erythroid cells to survive, proliferate and differentiate. During RBCs aging and injury, macrophages play a fundamental role again, performing the clearance of these cells and recycling iron for new erythroblasts in development. Thus, macrophages are crucial components of the RBCs turnover and in this review, we aimed to cover the main known mechanisms involved in the process of birth and death of RBCs, highlighting the importance of macrophage functions in the whole RBC lifecycle.

Hemoglobina reticulocitaria y su utilidad clínica en el diagnóstico temprano de eritropoyesis por deficiencia de hierro absoluto en mujeres adolescentes / Reticulocyte hemoglobin and its clinical utility in the early diagnosis of erythropoiesis due to absolute iron deficiency in adolescent women / Hemoglobina de reticulócitos e sua utilidade clínica no diagnóstico precoce da eritropoiese por deficiência absoluta de ferro em mulheres adolescentes

La hemoglobina reticulocitaria es un nuevo parámetro dentro de los autoanalizadores hematológicos de cuarta generación, siendo indispensable en el diagnóstico y manejo de eritropoyesis deficiente en hierro, especialmente la deficiencia funcional de hierro, el secuestro de hierro y la deficiencia absoluta de hierro. Además, este parámetro demuestra ser más preciso que las pruebas bioquímicas como el hierro sérico, la ferritina y la saturación de transferrina, en la detección precoz de eritropoyesis deficiente en hierro. El objetivo de la investigación fue describir la utilidad clínica de la hemoglobina reticulocitaria (CHr) en el diagnóstico temprano de eritropoyesis por deficiencia de hierro absoluto en mujeres adolescentes. El tipo de investigación fue descriptivo, analítico, el diseño de campo transversal. La muestra voluntaria, no aleatoria estuvo constituida por 62 mujeres adolescentes con edades comprendidas entre los 14 y 19 años. Como resultado se encontró que el 97% de la muestra tiene disminución de la CHr, indicando eritropoyesis deficiente en hierro, mientras que un 3% de las adolescentes presentan valores normales para la CHr, se realizó la relación diagnostica entre pruebas de laboratorio tales como CHr y el Hierro sérico. También se reportó que el 93% de la muestra presenta déficit de hierro sin anemia, y un 7% tiene anemia ferropénica, el rango de edad con mayor predominio de anemia ferropénica fue entre los 14 y 16 años. Se concluye que la CHr es de utilidad clínica y una nueva herramienta de diagnóstico temprano de eritropoyesis por deficiencia de hierro.

Reticulocyte hemoglobin is a new parameter within the fourth generation hematological autoanalyzers, being indispensable in the diagnosis and management of iron deficient erythropoiesis, especially functional iron deficiency, iron sequestration and absolute iron deficiency. Moreover, this parameter proves to be more accurate than biochemical tests such as serum iron, ferritin and transferrin saturation in the early detection of iron deficient erythropoiesis. The aim of the research was to describe the clinical utility of reticulocyte hemoglobin (CHr) in the early diagnosis of absolute iron deficiency erythropoiesis in adolescent females. The type of research was descriptive, analytical, cross-sectional field design. The voluntary, non-random sample consisted of 62 adolescent females aged between 14 and 19 years. As a result, it was found that 97% of the sample had decreased CHr, indicating iron deficient erythropoiesis, while 3% of the adolescents had normal values for CHr. The diagnostic relationship between laboratory tests such as CHr and serum iron was performed. It was also reported that 93% of the sample presented iron deficiency without anemia, and 7% had iron deficiency anemia; the age range with the highest prevalence of iron deficiency anemia was between 14 and 16 years of age. It is concluded that HRH is clinically useful and a new tool for early diagnosis of erythropoiesis due to iron deficiency.

A hemoglobina reticulócita é um novo parâmetro dentro da quarta geração de auto-analisadores hematológicos, sendo indispensável no diagnóstico e manejo da eritropoiese com deficiência de ferro, especialmente deficiência funcional de ferro, seqüestro de ferro e deficiência absoluta de ferro. Além disso, este parâmetro prova ser mais preciso do que testes bioquímicos como ferro sérico, ferritina e saturação da transferrina na detecção precoce de eritropoiese com deficiência de ferro. O objetivo da pesquisa foi descrever a utilidade clínica da hemoglobina reticulocitária (RCHr) no diagnóstico precoce da eritropoiese absoluta de deficiência de ferro em mulheres adolescentes. O tipo de pesquisa foi descritivo, analítico, de corte transversal do campo. A amostra voluntária e não aleatória consistiu de 62 fêmeas adolescentes com idades entre 14 e 19 anos. Como resultado, descobriu-se que 97% da amostra tinha uma diminuição na HRH, indicando uma eritropoiese com deficiência de ferro, enquanto 3% das adolescentes tinham valores normais para HRH. Também foi relatado que 93% da amostra tinha deficiência de ferro sem anemia, e 7% tinha anemia por deficiência de ferro; a faixa etária com maior prevalência de anemia por deficiência de ferro era entre 14 e 16 anos. Conclui-se que o RHH é clinicamente útil e uma nova ferramenta para o diagnóstico precoce da eritropoiese devido à deficiência de ferro.

Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis / 中华血液学杂志

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.

Do blood parasites increase immature erythrocytes and mitosis in amphibians? / ¿Causan los parásitos sanguíneos un aumento en los eritrocitos inmaduros y la mitosis en los anfibios?

Abstract Introduction: In amphibians, blood may act as a hematopoietic tissue. However, the knowledge concerning hematological features is scarce, there is not much information that allows an analysis about the possible explanations of this physiological feature. Objective: This study aimed to evaluate the relationship between immature red blood cells (RBCs) mitosis and the presence of blood parasites in amphibians. Methods: We sampled 116 amphibians (31 species) in six Colombian localities. Blood was taken by cardiac puncture or maxillary vein puncture. Smears were prepared, fixed, and Giemsa stained for microscopical analysis. The variables analyzed were the percentage of immature RBCs, mitotic cells in peripheral blood, and blood parasite infection. Data were analyzed using Wilcoxon's rank test and exact Fisher statistical tests. Results: Sixty-two individuals showed mitosis in peripheral blood, and these mitotic RBCs shared morphological features with immature RBCs. Overall, parasite prevalence was 30.1 %, distributed as follows: Trypanosoma (24.1 %), Hepatozoon-like (6 %), Dactylosoma (4.3 %), Karyolysus-like (0.9 %), and Filarioidea (2.6 %). A positive association between the percentage of immature RBCs and the presence of mitotic RBCs was found, and also between the blood parasite infection and the percentage of immature RBCs. Conclusions: In this study, we found that the presence of blood parasites, immature RBCs, and RBCs mitosis are frequent events in amphibians' peripheral blood, and our analysis suggests an association between those features. Thus, the release of immature RBCs and the mitosis of those cells in peripheral blood may be a physiological response to blood parasite infection. Further studies characterizing hematology in amphibians and wildlife, in general, are desirable.

Resumen Introducción: En anfibios, la sangre puede actuar como un tejido hematopoyético. Sin embargo, el conocimiento acerca de las características hematológicas es escaso y no hay información que permita un análisis acerca de las posibles explicaciones a este rasgo fisiológico. Objetivo: La intención de este estudio fue evaluar la relación entre la presencia de eritroblastos, mitosis de glóbulos rojos (GRs) y la infección por hemoparásito en sangre periférica de anfibios. Métodos: Se muestrearon 116 anfibios (31 especies) en seis localidades de Colombia. Se tomaron muestras de sangre mediante punción cardiaca o punción a la vena maxilar. Se prepararon extendidos sanguíneos, se fijaron y tiñeron con Giemsa para su posterior análisis por microscopía. Se analizaron variables como porcentaje de GRs inmaduros, células mitóticas en sangre periférica e infección por hemoparásitos. Los datos fueron analizados mediante el test de rango de Willcoxon y el test exacto de Fisher. Resultados: sesenta y dos individuos evidenciaron mitosis en sangre periférica y dichas mitosis compartían características morfológicas con GRs inmaduros. La prevalencia general de parásitos fue del 30.1 %, distribuido de la siguiente forma: Trypanosoma (24.1 %), Hepatozoon-like (6 %), Dactylosoma (4.3 %), Karyolysus-like (0.9 %), y Filarioidea (2. 6 %). Hay una asociación positiva entre el porcentaje de GRs inmaduros y la presencia de células mitóticas, también se encontró una relación entre la infección por hemoparásitos y el porcentaje de GRs inmaduros. Conclusiones: En este estudio encontramos que la presencia de parásitos sanguíneos, GRs inmaduros y mitosis de GRs son eventos frecuentes en sangre periférica de anfibios, y nuestros resultados sugieren una asociación entre dichas características. Por tanto, la liberación de GRs inmaduros y la mitosis de estas células en sangre periférica podría ser una respuesta fisiológica a infecciones parasitarias. Posteriores estudios que caractericen la hematología en anfibios y en vida silvestre en general, son deseables.

Markers of ineffective erythropoiesis in non-transfusion dependent β-thalassaemia

@#Non-transfused β-thalassaemia patients develop complications related to unsuppressed ineffective erythropoiesis (IE). Serum markers of IE would be useful for risk stratification and monitoring treatment. We studied βthalassaemia trait (β-TT) and non-transfusion-dependent βthalassaemia (β-NTDT) patients. Serum erythropoietin (EPO) and soluble transferrin receptor (sTfR) were correlated against markers of clinical severity (haemoglobin, LDH, retics, bilirubin, spleen size) and iron overload (ferritin, hepcidin, and MRI-T2* in NTDT patients). Eleven β-NTDT and nine β-TT subjects were studied. βNTDT patients had significantly higher markers of haemolysis and iron overload. In β-NTDT, liver iron ranged from mild to severe, but no cardiac loading was seen. EPO and sTfR were higher in patients with β-NTDT than β-TT, and correlated significantly with each other (ρ=0.630, p=0.003). Both markers were negatively correlated with haemoglobin (sTfR ρ=-0.540, p=0.014; EPO ρ=-0.807, p<0.001, and positively correlated with spleen size (sTfR ρ=0.783, p<0.001; EPO ρ=0.654, p=0.002) and markers of iron overload. There was a strong correlation between ferritin and hepcidin (ρ=0.720, p<0.001), and a relatively lower increment of hepcidin for the degree of iron overload in βNTDT compared to β-TT. EPO and sTfR appear to be reliable markers of erythropoiesis in non-transfused β-thalassaemia and correlate well with markers of disease severity. Their role in managing patients, predicting complications, and monitoring response to treatments aimed at reducing IE should be explored.

A prospective observational study on the effect of Erythropoiesis stimulating agents in chronic kidney disease Anemia patients

Background and Objectives: Anemia is a frequent complication, and significant morbidity and mortality in patient with chronic kidney disease (CKD). Erythropoiesis Stimulating Agents (ESAs) have become the standard care for anemia t erapy and reduces need for blood transfusions. The bjective of the study was to evaluate the safety and effect of ESAs and to create the awareness among patients regarding the Erythropoiesis stimulating agents through patient i formation leaflets.Methods: The prospective observational study of 6-month duration was conducted in a tertiary care hospital. A total of 162 patients on ESAs were enrolled in the study. Patients were followed for continuously and the mean difference is assessed by monitoring the primary and secondary hematological parameters before and after ESAs administration. Patient information leaflet was given t the patients for education and awareness about ESAs.Results: Out of 162 patients, after the administration of ESAs mean value increase in hemoglobin level was found from base line 6.9g/dL to 11.6g/dL. Significant improvement was noted in CKD anemia patient indicating impact of patient counseli g.Conclusion: It can be concluded that Erythropoiesis Stimulating Agents in treatment of anemia along with effective counseling from clinical pharmacist benefits CKD patients and improves the health outcomes.

Antioxidant potential of Carica papaya Linn (Caricaceae) leaf extract in mice with cyclophosphamide induced oxidative stress / Potencial antioxidante do extrato de folhas de Carica papaya Linn (Caricaceae) em camundongos com estresse oxidativo induzido por ciclofosfamida

AIMS: This study aimed to investigate the effects of crude extract of Carica papaya leaves on oxidative stress in mice induced by cyclophosphamide, as well as phytochemical profile characterization of this extract. METHODS: The male Swiss mice received 15 days of treatment with the extract (500 mg kg-1, via gavage) and intraperitoneal injection of cyclophosphamide (75 mg kg-1) or saline (0.9%) on the 15th day. After 24 h the last treatment, the animals were anesthetized for blood withdrawal, sacrificed and removal of the organs for analyses (liver, kidney and heart). In the biochemical tests were determined: hematological parameters in blood, aminotransferases, alkaline phosphatase, glucose and total cholesterol dosages in plasma, enzymatic and non-enzymatic antioxidants and lipid damage marker were evaluated in different tissues, besides genotoxic and histopathological analyzes. RESULTS: In the extract of Carica papaya leaves, the flavonoids quercetin-3ß-D-glucoside and rutin were identified, besides present positive results for alkaloids, saponins and tannins. This extract increased the activity of glutathione-S-transferase and catalase enzymes in the liver and reduced the levels of reduced glutathione in the kidneys and hematocrit levels, red cell count, and hemoglobin. It promoted the decrease of the reactive species of thiobarbituric acid (TBARS) in the kidneys and the activity of enzyme aspartate aminotransferase in the plasma and was antimutagenic in the micronucleus test. CONCLUSIONS: The study showed that extract of Carica papaya was beneficial against oxidative events and prevented DNA damage. The extract also showed hepatotoxicity, therefore prolonged infusion of papaya leaves is not advisable.

OBJETIVOS: O objetivo deste estudo foi investigar os efeitos do extrato bruto de folhas de Carica papaya sobre o estresse oxidativo em camundongos induzidos pela ciclofosfamida, bem como a caracterização do perfil fitoquímico deste extrato. MÉTODOS: Os camundongos Swiss machos receberam 15 dias de tratamento com o extrato (500 mg kg-1, via gavagem) e injeção intraperitoneal de ciclofos-famida (75 mg kg-1) ou salina (0,9%) no 15º dia. Após 24 h do último tratamento, os animais foram anestesiados para retirada do sangue, sacrificados e retirada dos órgãos para análises (fígado, rim e coração). Nos testes bioquímicos foram determinados: parâmetros hematológicos em sangue, aminotransferases, fosfatase alcalina, dosagens de glicose e colesterol total no plasma, antioxidantes enzimáticos e não enzimáticos e marcador de dano lipídico foram avaliados em diferentes tecidos, além de análises genotóxicas e histopatológicas. RESULTADOS: No extrato de folhas de Carica papaya foram identificados os flavonoides quercetina-3ß-D-glicosídeo e rutina, além de resultados positivos para alcaloides, saponinas e taninos. Este extrato aumentou a atividade das enzimas glutationa-S-transferase e catalase no fígado e diminuiu os níveis de glutationa reduzida nos rins, a concentração do hematócrito, a contagem dos glóbulos vermelhos e a hemoglobina. Promoveu a diminuição das espécies reativas de ácido tiobarbitúrico (TBARS) nos rins, a atividade da enzima aspartato aminotransferase no plasma e foi antimuta-gênico no teste do micronúcleo. CONCLUSÕES: O estudo mostrou que o extrato de Carica papaya foi benéfico contra eventos oxidativos e preveniu danos no DNA. O extrato também mostrou hepatotoxicidade, portanto, a infusão prolongada de folhas de mamão não é aconselhável.

Macrophages can regulate bone homeostasis and erythropoiesis: Problems and prospects / 中国组织工程研究

BACKGROUND: Regulation of erythropoiesis in the bone marrow microenvironment is a carefully orchestrated process dependent upon systemic and local cues. Systemic erythropoietin production by renal interstitial cells plays a critical role in maintaining erythropoietic homeostasis. Increasing evidences have shown that erythropoietin and erythropoiesis can alter skeletal homeostasis, suggesting a functional relationship between the regulation of erythropoiesis and bone homeostasis. In recent years, macrophages play a regulatory role in erythropoietin, bone homeostasis and erythropoiesis. OBJECTIVE: To summarize the research advance concerning the role of macrophages in erythropoiesis and bone homeostasis. METHODS: PubMed, Medline, Web of Science, Wanfang and CNKI databases were retrieved with the keywords of “erythropoiesis, macrophage, erythropoietin, bone formation, bone homeostasis” in English and Chinese, respectively for relevant articles published from January 1999 to October 2019. Finally 48 articles eligible for inclusion and exclusion criteria were included for further analysis. RESULTS AND CONCLUSION: As key local components of the bone marrow microenvironment and erythropoietic niche, macrophage subsets play important roles in both processes. Peritoneum macrophages, glial macrophages and liver resident macrophages promote the production of erythropoietin in renal interstitium. Bone marrow macrophages or osteoma, osteoclasts and central macrophages regulate bone homeostasis, and further promote erythropoiesis.

A link between long non-coding RNA (lncRNA) and thalassaemia: A review

@#The long non-coding RNAs (lncRNAs) are the most prevalent and functionally diverse member of the non-coding RNA (ncRNA). The lncRNA has previously been considered to be a form of transcriptional “noise” but recent studies have found that the lncRNA to be associated with various disease conditions. It has also been found to play important roles in various physiological processes such as haemopoiesis, where lncRNA is reported to act as a fine-tuner of this very important process. To date, the effects of dysregulated lncRNA in thalassaemia has not been fully explored. This review article focuses on the possible roles of dysregulated lncRNAs in the pathogenesis of thalassaemia.

Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches

Major beta thalassemia is a severe form of thalassemia caused by the alteration of two beta globin genes resulting in a defective synthesis of hemoglobin. It is characterized by chronic severe anemia, ineffective erythropoiesis (IE) and iron overload. However although the thransfusion and chelation assosciated constitute the basis of the traitement curently recommended, they do not allow always to control the iron overload induced by pathology and repeated transfusions. Hematopoietic stem cell transplantation (HSCT) has proven to be a definitive treatment for beta thalassemia. However, this procedure is confronted to immunological complications and the small nomber of histocompatible donors. In the face of these therapeutic blocks, much research has been undertaken in recent years leading to the development of a number of promising therapeutic strategies in order to reduce the constraints linked to current chronic treatments, and to move towards an access to healing for all patients. Among other three approaches are envisaged and are in the experimental phase: Gene therapy to restore globin chain imbalance, Improve ineffective erythropoiesis and Improve iron dysregulation. In this article we give a view on the pathophysiology, clinical manifestations, genetic origin of beta-thalassaemia major. The second part presents the therapeutic arsenal currently used, and its limits leading to therapeutic impasse. The last part explores the scientific tracks that present a real therapeutic potential in ?-Thalassemia.

Advances on erythropoietin treatment of anemia in prematurity infants / 中华实用儿科临床杂志

Anemia is one of the common complications in preterm infants.Although there are many factors that can cause anemia of prematurity (AOP), erythropoietin (EPO) deficiency is one of the main causes of AOP.Insufficient EPO levels in premature infants and their mechanisms are the hotspots of AOP research at home and abroad.The rational use of EPO for prevention and treatment of AOP has become an international consensus and significant clinical outcomes have been obtained.The recent progress in the field of AOP, the relationship between EPO and AOP, and the clinical application and efficacy of EPO in the prevention and treatment of AOP in recent 3 to 5 years have been reviewed.

Advances on erythropoietin treatment of anemia in prematurity infants / 中华实用儿科临床杂志

Anemia is one of the common complications in preterm infants.Although there are many factors that can cause anemia of prematurity (AOP),erythropoietin (EPO) deficiency is one of the main causes of AOP.Insufficient EPO levels in premature infants and their mechanisms are the hotspots of AOP research at home and abroad.The rational use of EPO for prevention and treatment of AOP has become an international consensus and significant clinical outcomes have been obtained.The recent progress in the field of AOP,the relationship between EPO and AOP,and the clinical application and efficacy of EPO in the prevention and treatment of AOP in recent 3 to 5 years have been reviewed.

The haemato-protective effect of Piliostigma thonningii leaf extract on indomethacin-induced gastric mucosa ulcer in rats

Background: Gastric ulcer is a common gastrointestinal disorder with global consequence, which is aggravated by an imbalance between the aggressive factors and factors that maintain the mucosal integrity. The role of Piliostigma thonningii leaf extract on hematological indices of indomethacin-induced gastric mucosa lesions in Wistar rats was examined.Methods: Thirty-six male rats were divided into six groups of 6 rats each. Group I, the normal control, II gastric ulcerated + cimetidine (standard control), III extract only (100mg/kg bwt), while IV, gastric ulcerated control, V gastric ulcerated + extract (100mg/kg bwt) and VI gastric ulcerated + extract (200mg/kg bwt). After 12 days of administration, gastric ulcer was then induced by oral administration of 40mg/kg bwt indomethacin to rats in groups II, IV, V and VI. The rats were sacrificed 12 hours after indomethacin treatment and blood collected for hematological assay.Results: The RBC count and Hb pattern were similar. There was a significant (P<0.05) decrease in RBC and Hb of the ulcer control group which was normalized on administration of 200mg/kg bwt of P. thonningii extract. The MCV of the ulcer lesion was significantly (P<0.05) reversed to normal by the extract.Conclusions: The P. thonningii leaf extract showed promising result by normalizing decreased levels in RBC and Hb caused by ulcer. Except for platelet counts, the WBC count and differential WBC counts were quite positive. It was able to reverse macrocytosis caused by ulcer lesions to normal, hence exhibiting a hemato-protective nature.

Incidence of iron deficiency anaemia and it’s early detection in patients with hypoproliferative anaemia presentation in a tertiary care hospital

Background: Iron deficiency anaemia still remains the most common cause of anaemia not only in India but also world over. According to world heath report, there are 1,788,600 people in this world suffering from Iron deficiency anaemia. Iron deficiency anaemia is foremost prevalent disease-causing morbidity in world and therefore it is always absolutely necessary to detect this particular condition in early stages before the eventual development of various dreadful complications like Heart failure and Myocardial infarction. The aim of the study is to find incidence of iron deficiency anaemia in patients with hypo proliferative anaemia presentation, with a possible iron deficient state, by analyzing the haematological and biochemical parameters.Methods: The study was conducted from November 2017 to May 2018 for a period of 6 months which included 50 subjects from both sex groups, aged 20-80 years with the diagnosis of hypo proliferative anaemia.Results: The study results indicate that females (60%) were significantly overrepresented compared to males (40%). Of the 50 subjects 38% were in stage of negative iron balance (stage1) and 32% were in stage of iron deficient erythropoiesis(stage2) and 30% were in normal stage.Conclusions: This Observational study showed a majority of patients with hypo-proliferative anaemia presenting at early stages of negative iron balance and iron deficient erythropoiesis thereby indicating the importance of initiating iron therapy at an early stage even without correlative iron studies.

Obesity may be erythropoietin dose-saving in hemodialysis patients

BACKGROUND: In dialysis patients, the obesity-survival paradox still requires an explanation. Anemia and high doses of erythropoiesis-stimulating agents (ESAs) are associated with worse outcomes in the hemodialysis (HD) population. In the present study, we explored the relation between obesity and anemia control in a sample of maintenance HD patients in Egypt. METHODS: This multicenter observational study included 733 patients on maintenance HD from 9 hemodialysis centers in Egypt. Clinical and laboratory data as well as average doses of ESAs and parenteral iron were recorded. The erythropoietin resistance index (ERI) was calculated. RESULTS: Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, was present in 22.6% of the studied population. The target hemoglobin level (10.0–11.5 g/dL) was achieved in 27.3% of non-obese and 25.3% of obese patients, with no significant difference. The median serum ferritin and the values of transferrin saturation index did not differ significantly between these two groups. The weekly ESA dose was significantly lower in obese than in non-obese patients (P = 0.0001). A trend toward higher ESA doses and ERI values was observed in patients with lower BMIs (P < 0.0001). Multiple linear regression revealed that the BMI and urea reduction ratio were the strongest predictors of the ERI. CONCLUSION: Our study adds more evidence to obesity-associated advantages in HD patients. BMI may determine ESA response, with better responses observed in patients with higher BMIs.

Niveles de eritropoyetina y reticulocitos en residentes de bajas alturas migrantes a medianas alturas / Erythropoietin and reticulocyte levels in lowland residents migrating to middle altitudes

RESUMEN Introducción: La eritropoyetina es una alfa globulina glicosilada con producción renal en más del 90% en la vida adulta. Es la principal hormona en el mantenimiento constante de la masa eritrocitaria, aunque existen modificaciones en sus niveles asociados con el tabaquismo, anemias, EPOC y la migración de bajas a medianas o altas alturas. Esto último desencadena un proceso hipóxico que puede llegar a producir mal agudo de montaña. Objetivo: Describir el comportamiento de la eritropoyetina, el recuento de reticulocitos y su influencia, en procesos de adaptación a la altura. Metodología: Estudio descriptivo de corte transversal que incluyó 11 participantes provenientes de bajas alturas a quienes se les determinó la concentración sérica de eritropoyetina y el recuento de reticulocitos en un periodo de 28 días. Resultados: Ocho de los participantes presentaron un ascenso progresivo en los niveles séricos de eritropoyetina, uno mantuvo una curva plana y dos presentaron comportamiento atípico respecto a lo reportado en la literatura. Conclusión: La eritropoyetina es un factor fundamental que marca el comienzo de la eritropoyesis, cuya finalidad es mejorar el aporte de oxígeno en procesos de adaptación a la altura. Además, la hipoxia es un factor determinante en el inicio y desarrollo del mal agudo de montaña. El recuento de reticulocitos depende del estímulo proliferativo y anti-apoptótico de la eritropoyetina, así como de las concentraciones séricas de vitamina B12, hierro y ácido fólico.

ABSTRACT Introduction: EPO is a glycosylated alpha globulin produced in more than 90% by kidneys through adult life, being a key hormone that regulated the erythrocytic mass. However, there are some modifications in the levels of this hormone that may be related to smoking, anemia, EPOC and migration to from low to higher altitudes, inducing hypoxic processes. Depending on the individual, it may produced the disease named as acute mountain sickness. Objective: To describe erythropoietin level modifications, reticulocytes count and its influence, on the adaptive process to altitude. Methodology: This is a transversal descriptive study including 11 participants from low altitudes places, whose EPO serum concentration and reticulocytes count was determined during 28 days. Results: Eight participants presented a progressive increase in EPO serum levels, one participant exhibited a constant level and two more showed atypical results according to previous literature. Conclusion: EPO is a key factor for determining the erythropoiesis beginning, as its objective is to improve the oxygen provision during altitude adaptation processes by increasing its concentration in blood due to hypoxic stimulus. Besides, hypoxia is a determinant factor in the beginning and development of acute mountain sickness. The reticulocytes count depends also on the EPO proliferative and anti-apoptotic stimulus, and on the serum concentrations of B12 vitamin, iron and folic acid.

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

Background: Tet methylcytosine dioxygenase 2 (TET2) is frequently mutated and/or downregulated in myeloid neoplasm, including myelodysplastic syndromes. Despite the extensive studies, the specific contribution of TET2 in disease phenotype of myeloid neoplasms is not fully elucidated. Recent findings have grown attention on the role of TET2 in normal and malignant erythropoiesis. Methods: In the present study, we investigated TET2 mRNA levels by quantitative PCR during erythropoietin-induced erythroid differentiation CD34+ cells from healthy donor and myelodysplastic syndrome patients. Statistical analyses were performed using the ANOVA and Bonferroni post hoc test and a p-value <0.05 was considered statically significant. Results: TET2 expression is upregulated during erythroid differentiation of CD34+ cells from healthy donor and myelodysplastic syndrome patients. Conclusions: Our findings corroborate that TET2 is involved in the erythrocyte differentiation (AU)

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

Regulation of the embryonic erythropoietic niche: a future perspective

The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1⁺ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1⁺ hepatoblasts in Map2k4(−/−) mouse embryos resulted in decreased numbers of hematopoietic cells in fetal liver. Genes encoding proteinases and peptidases were found to be highly expressed in DLK1⁺ hepatoblasts. Capitalizing on this knowledge, and working on the assumption that these proteinases and peptidases are generating small, potentially biologically active peptides, we assessed a range of peptides for their ability to support erythropoiesis in vitro. We identified KS-13 (PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the production of red blood cells from progenitor cells. Here, we discuss the elements regulating embryonic erythropoiesis with special attention to niche cells, and demonstrate how this knowledge can be applied in the identification of niche-derived peptides with potential therapeutic capability.