Erythropoietin In Combination Research Articles

The combined use of erythropoietin and iron preparations for the management of postpartum anemia: a systematic review and meta-analysis

INTRODUCTION: There are limited data on the effectiveness of erythropoietin in combination with oral ferrotherapy for the management of postpartum anemia. OBJECTIVE: To evaluate the efficacy of erythropoietin in combination with oral iron compared with oral ferrotherapy in puerperas with postpartum haemorrhage. MATERIALS AND METHODS: MEDLINE, Scopus, EBSCOhost and 5 other databases (January 1980 to February 2023) were searched for articles on the use of oral iron in combination with and without erythropoietin for the treatment of post-hemorrhagic anemia in puerperas. Primary outcomes: hemoglobin level, hemoglobin increase, hematocrit, number of blood transfusions, secondary outcomes: ferritin level, serum iron, lactation capacity. The analysis was carried out in accordance with the PRISMA guidelines, 2020. RESULTS: 4 studies were analyzed, 198 women were included. When using erythropoietin in combination with oral ferrotherapy, the cumulative value of the increase in hemoglobin concentration after 5 days, 2 weeks of treatment was significantly higher compared with the control group (mean difference [MD]: 11.83 g/L, 95% CI 4.43–19.23; р = 0.002, MD 10.13 g/L, 95% CI 4.97–15.29; р = 0.0001), respectively. The cumulative mean hemoglobin concentration after 40 days of treatment was significantly higher in the erythropoietin group (MD 11.00 g/L, 95% CI 1.70–20.30; р = 0.02). The cumulative mean hematocrit after 2 weeks of treatment was significantly higher in the erythropoietin group (MD 3.35 %, 95% CI 0.31–6.39; р = 0.03). The use of erythropoietin in combination with oral iron reduces the likelihood of blood transfusion (relative risk 0.12, 95% CI 0.02–0.95; р = 0.04). CONCLUSIONS: A faster hematological response was shown with the combined use of erythropoietin with oral ferrotherapy compared with monotherapy with iron preparations in the management of postpartum anemia. Further studies with sufficient sample sizes are required.

Preoperative Epoetin-α with Intravenous or Oral Iron for Major Orthopedic Surgery: A Randomized Controlled Trial.

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Preoperative administration of epoetin-α with iron is commonly used in anemic patients undergoing major orthopedic surgery, but the optimal route of iron intake is controversial. The aim of this study was to compare the clinical effects of erythropoietin in combination with oral or intravenous iron supplementation. This study was a prospective, randomized, single-blinded, parallel arm trial. Patients scheduled for elective hip or knee arthroplasty with hemoglobin 10 to 13 g/dl received preoperative injections of erythropoietin with oral ferrous sulfate or intravenous ferric carboxymaltose. The primary endpoint was the hemoglobin value the day before surgery. One hundred patients were included in the analysis. The day before surgery, hemoglobin, increase in hemoglobin, and serum ferritin level were higher in the intravenous group. For the intravenous and oral groups, respectively, hemoglobin was as follows: median, 14.9 g/dl (interquartile range, 14.1 to 15.6) versus 13.9 g/dl (interquartile range, 13.2 to 15.1), group difference, 0.65 g/dl (95% CI, 0.1 to 1.2; P = 0.017); increase in hemoglobin: 2.6 g/dl (interquartile range, 2.1 to 3.2) versus 1.9 g/dl (interquartile range, 1.4 to 2.5), group difference, 0.7 g/dl (95% CI, 0.3 to 1.1; P < 0.001); serum ferritin: 325 µg/l (interquartile range, 217 to 476) versus 64.5 µg/l (interquartile range, 44 to 107), group difference, 257 µg/l (95% CI, 199 to 315; P < 0.001). The percentage of patients with nausea, diarrhea, or constipation was higher in the oral group, 52% versus 2%; group difference, 50% (95% CI, 35 to 64%; P < 0.0001). After preoperative administration of erythropoietin, body iron stores and stimulation of the erythropoiesis were greater with intravenous ferric carboxymaltose than with oral ferrous sulfate supplementation.

The effects of erythropoietin, dextran and saline on brain edema and lipid peroxidation in experimental head trauma.

The aim of this study was to investigate the protective effects of erythropoietin, dextran/saline and erythropoietin in combination with dextran/saline on brain edema and lipid peroxidation following traumatic brain injury in rats. In the study, 40 male 3-month-old albino Wistar rats, weighing 250-340 g, were divided into four groups, each consisting of ten rats. Traumatic brain injury was induced in all rats by the weight-drop method, and erythropoietin (5,000 U/kg) and/or dextran and saline (8 ml/kg) solutions were injected intraperitoneally ten minutes after trauma. Control animals received an equal volume of serum physiologic. All rats were sacrificed 24 hours later. Glutathione peroxidase activity and malondialdehyde levels were measured in the left hemisphere, and edema was quantitated by the wet-dry method. Brain edema and the levels of malondialdehyde, the last product of lipid peroxidation in tissues, were decreased variably, and the activity of glutathione peroxidase, an antioxidant enzyme, was increased in others compared with the control group. In this study, it was concluded that the brain edema that developed in rats on which head trauma was induced and the secondary brain damage caused by oxidative stress could be deceased using a combination of erythropoietin, dextran, and saline.

Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.

BackgroundSeveral studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.MethodsHuman tumours from oral squamous cell cancer were xenotransplanted to nude mice treated with Epo. The tumours were then transected in a standardised procedure to mimic surgical trauma and the change in gene expression of the tumours was investigated by microarray analysis. qRT-PCR was used to measure the levels of mRNAs of pro-apoptotic genes. The frequency of apoptosis in the tumours was assessed using immunohistochemistry for caspase-3.ResultsThere was little change in the expression of genes involved in tumour growth and angiogenesis but a significant down-regulation of the expression of genes involved in apoptosis. This effect on apoptosis was confirmed by a general decrease in the expression of mRNA for selected pro-apoptotic genes. Epo-treated tumours had a significantly lower frequency of apoptosis as measured by immunohistochemistry for caspase 3.ConclusionsOur results suggest that the increased tumour growth during erythropoietin treatment might be due to inhibition of apoptosis, an effect that becomes significant during tissue damage such as surgery.This further suggests that the decreased survival during erythropoietin treatment might be due to inhibition of apoptosis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-648) contains supplementary material, which is available to authorized users.

Anemia in Pregnancy &amp; Parenteral Iron Therapy

Anemia is common in pregnancy and iron deficiency is the most common cause. Oral iron is the standard therapy, but there is a problem of adherence due the gastrointestinal side effects. Intravenous iron therapy has more advantages, therefore, intravenous iron therapy is the best treatment for pregnant women during the third trimester. We reviewed the statistics of deliveries of the fiscal year 2012, the cases of anemia in pregnancy as in patients provided by Record Room from the calendar year 2012 and the patient cases that used sodium ferric gluconate complex in sucrose injection (FERRLECIT) from the Obstetrics/Gynecology Ward from the fiscal year 2012 provided by the Department of Pharmacy of the Ashford Presbyterian Community Hospital (APCH). A review of the records of pregnant women receiving iron dextran injection (INFeD) intravenously in our ambulatory infusion center was also performed. Our data confirmed that either presentations elevated the hemoglobin and they were well tolerable. Iron sucrose is the preferred and it has demonstrated a high success rate. I recommend considering this alternative earlier at the third trimester and establishing guidelines using parenteral iron and erythropoietin in combination in refractory cases.

Erythropoietin in Combination of Tissue Plasminogen Activator Exacerbates Brain Hemorrhage When Treatment Is Initiated 6 Hours After Stroke

Erythropoietin (EPO), a hematopoietic cytokine, exerts neuroprotective effects in experimental stroke. In the present study, we investigated the effect of recombinant human EPO (rhEPO) in combination with tissue plasminogen activator (tPA) on embolic stroke. Rats subjected to embolic middle cerebral artery occlusion (MCAO) were treated with rhEPO (5000 U/kg) in combination with tPA (10 mg/kg) at 2 or 6 hours after MCAO. Control groups consisted of ischemic rats treated with rhEPO (5000 U/kg) alone, tPA (10 mg/kg) alone, or saline at 2 or 6 hours after MCAO. The combination therapy of rhEPO and tPA initiated 6 hours after MCAO did not reduce the ischemic lesion volume and significantly (P<0.05) increased the incidence of brain hemorrhage measured by frequency of gross hemorrhage and a quantitative spectrophotometric hemoglobin assay compared with rats treated with rhEPO alone and tPA alone. However, when the combination therapy was initiated 2 hours after MCAO, the treatment significantly (P<0.05) reduced the lesion volume and did not substantially increase the incidence of hemorrhagic transformation compared with saline-treated rats. Immunostaining analysis revealed that the combination therapy of rhEPO and tPA at 6 hours significantly (P<0.05) increased matrix metalloproteinase-9, NF-kappaB, and interleukin-1 receptor-associated kinase-1 immunoreactive cerebral vessels compared with rats treated with rhEPO alone and saline. EPO exacerbates tPA-induced brain hemorrhage without reduction of ischemic brain damage when administered 6 hours after stroke in a rat model of embolic MCAO and that matrix metalloproteinase-9, NF-kappaB, and interleukin-1 receptor-associated kinase-1 upregulated by the delayed combination therapy may contribute to augmentation of brain hemorrhage.

Therapie der chronischen Entzündungsanämie – Eisen, Bluttransfusionen oder Erythropoetin?

The anaemia of chronic disease is a concomitant phenomenon of various chronic intectious, neoplastic and autoimmune diseases. Whenever possible, the treatment of the underlying disease is the treatment of choice. When this is not feasible at present blood transfusion, iron therapy and the use of erythropoietic agents are further treatment options. Blood transfusions are reserved for the short-term use in the case of life-threatening anaemia (Hb 100 μg/L) without functional iron deficiency should not be treated with iron. The erythropoietic stimulation with the currently available agents epoetin alfa, epoetin beta and darbepoetin can result in a nearly 100% therapeutic response provided the individual iron requirements are considered. Using erythropoietin in combination with iron in patients with RA und ACD, it has been shown that besides the correction of the haemoglobin deficit also disease activity as well as health-related quality of life could be approved. The risk-benefit ratio of the treatment of ACD regarding the underlying disease has, however, not been fully evaluated so far. This is also true for the use of iron and erythropoietin in the treatment of ACD. Further therapeutic options such as the use of iron chelating agents or other agents with an influence on the regulation of the cellular iron metabolism are in preclinical evaluation. It can, however, already be stated with regard to an appropriate management of patients with rheumatic diseases, regardless of the underlying disease, that ACD can be treated effectively.

New Possibili­ties for Prevention and Treatment of Iron Deficiency Posthemorrhagic Anemia after Traumatologic and Ortho­paedic Interventions in Children

The aim of the study was to elaborate complex therapy for correction of intraoperative blood loss and posthemorrhagic anemia following trauma and orthopaedic surgery in children. Seventy-six patients with orthopaedic pathology, 1—18 aged, were operated on. Blood loss volume was over10% of CBV. In 46 patients (main group) reinfusion of washed erythrocytes was performed when planning operative blood loss exceeded 25% of CBV. In patients over 7(34 patients) preoperative stimulation of erythropoiesis by erythropoietin in combination with peroral ferric drugs as well as pre- and intraoperative blood intake with subsequent it utilization were carried out. At postoperative period all patients of main group took Venifor i.v. to correct ferric deficit. In control group (30 patients) intraoperative blood loss and postoperative anemia were corrected by infusion of donor blood. Use of complex measures directed to support the hemopoietic function and correct the number of functionally active erythrocytes (main group) allowed to stabilize oxy­genous blood volume and decrease the hemolysis degree in patients after surgical intervention.

Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors

AbstractLow-risk myelodysplastic syndromes (MDS), including refractory anemia and sideroblastic anemia, are characterized by increased apoptotic death of erythroid progenitors. The signaling pathways that elicit this pathologic cell death in MDS have, however, remained unclear. Treatment with erythropoietin in combination with granulocyte colony-stimulating factor (G-CSF) may synergistically improve the anemia in patients with MDS, with a concomitant decrease in the number of apoptotic bone marrow precursors. Moreover, we have previously reported that G-CSF inhibits Fas-induced caspase activation in sideroblastic anemia (RARS). The present data demonstrate that almost 50% of erythroid progenitor cells derived from patients with MDS exhibit spontaneous release of cytochrome c from mitochondria with ensuing activation of caspase-9, whereas normal erythroid progenitors display neither of these features. G-CSF significantly inhibited cytochrome c release and suppressed apoptosis, most noticeably in cells from patients with sideroblastic anemia. Furthermore, inhibition of caspase-9 suppressed both spontaneous and Fas-mediated apoptosis of erythroid progenitors in all low-risk MDS cases studied. We propose that the increased sensitivity of MDS progenitor cells to death receptor stimulation is due to a constitutive activation of the mitochondrial axis of the apoptotic signaling pathway in these cells. These studies yield a mechanistic explanation for the beneficial clinical effects of growth factor administration in patients with MDS, and provide a model for the study of growth factor–mediated suppression of apoptosis in other bone marrow disorders.

Effects of hydroxurea, stem cell factor, and erythropoietin in combination on fetal hemoglobin in the baboon.

Augmentation of the level of fetal hemoglobin (HbF) is considered therapeutic for patients with sickle cell disease. The objective of this study was to determine the effect of treatment with a combination of erythropoietin (Epo), stem cell factor (SCF), and hydroxyurea (HU) on HbF levels. The effect of treatment with a combination of Epo, SCF, and HU on HbF, F-cell numbers, and globin chain synthesis was evaluated in a baboon model. Treatment with a combination of SCF+Epo resulted in a two-fold increase in HbF, F-cells, and F-reticulocytes compared to Epo alone. The combination of SCF+Epo+HU resulted in an additional two-fold increase in HbF, whereas F-cells and F-reticulocytes increased only 25% compared to the SCF+Epo regimen. Measurement of differential globin chain synthesis indicated that the SCF+Epo+HU treatment also increased the I gamma/V gamma (homologous to human G gamma and A gamma) synthetic ratio toward the fetal ratio. HU can effectively augment growth factor-induced HbF synthesis in vivo. Because I gamma/V gamma ratios are unaffected by erythropoietic stress and similar increases in this ratio have only been observed following administration of 5-azacytidine, we suggest that these two agents may share a common mechanism of action involving the recruitment of a similar target cell population to terminal erythroid differentiation.

Bloodless Pediatric Cardiac Surgery? Deliverance with Erythropoietin

A 2-year-old 11.6 kg boy with congenital heart disease whose parents refused homologous blood products was treated preoperatively with iron and human recombinant erythropoietin for 6 weeks. Surgical repair was performed without exposure to blood products other than human albumin. Treatment with iron and erythropoietin in combination with post-bypass modified ultrafiltration, minimization of hemodilution, reinfusion of residual pump prime, and diuresis may reduce or avoid the need for blood transfusion in acyanotic children undergoing elective cardiac surgery.

Fetal hemoglobin induction with butyric acid: efficacy and toxicity

Butyric acid induces fetal hemoglobin (HbF), a property of potential therapeutic advantage in patients with disorders of globin chain synthesis. We performed dose escalation studies of this compound in baboons to assess whether clinically significant increases in HbF are achievable, and to define the associated toxicities. Additionally, the effect of butyrate in combination with erythropoietin on HbF induction was assessed. HbF induction in response to butyrate was dependent on the dose and duration of treatment. Doses of butyrate less than 4 g/kg/d were associated with minimal toxicity (hypokalemia) and significant HbF induction in these nonanemic animals, with 1 g/kg/d producing an increase in HbF-containing reticulocytes (F reticulocytes) from 0.9% to 8.7% and an increase in HbF from 0.8% to 1.4%. A dose of 2 g/kg/d resulted in an increase in F reticulocytes from 2.1% to 27.8% and an increase in HbF from 0.7% to 2.2%. Doses of 4 g/kg/d in another animal produced an increase in F reticulocytes from 1% to 21.6% and in HbF from 1.9% to 5.3%. Infusions in excess of 4 g/kg/d were complicated (after a variable amount of time) by a decreased level of alertness (caused by hyperosmolality or butyrate itself) and hematologic toxicity (with declines in reticulocyte, white blood cell, and platelet counts). Prolonged infusions of high doses of butyrate (8 to 10 g/kg/d) were associated with peak F reticulocyte percentages reaching 38% to 64.5% and HbF reaching levels in excess of 20%. These high doses (8 to 10 g/kg/d) were complicated in two animals with a striking and unique neuropathologic picture and, in one animal, multiorgan system failure. Erythropoietin in combination with butyrate, induced F reticulocytosis in an additive manner. We conclude that butyric acid is a strong inducer of HbF, particularly when administered in combination with erythropoietin. As chronic toxicities remain undefined, patients in future clinical trials of this and similar compounds should be monitored closely for evidence of neurologic toxicity.

Fetal Hemoglobin Induction With Butyric Acid: Efficacy and Toxicity

AbstractButyric acid induces fetal hemoglobin (HbF), a property of potential therapeutic advantage in patients with disorders of globin chain synthesis. We performed dose escalation studies of this compound in baboons to assess whether clinically significant increases in HbF are achievable, and to define the associated toxicities. Additionally, the effect of butyrate in combination with erythropoietin on HbF induction was assessed. HbF induction in response to butyrate was dependent on the dose and duration of treatment. Doses of butyrate less than 4 g/kg/d were associated with minimal toxicity (hypokalemia) and significant HbF induction in these nonanemic animals, with 1 g/kg/d producing an increase in HbF-containing reticulocytes (F reticulocytes) from 0.9% to 8.7% and an increase in HbF from 0.8% to 1.4%. A dose of 2 g/kg/d resulted in an increase in F reticulocytes from 2.1 % to 27.8% and an increase in HbF from 0.7% to 2.2%. Doses of 4 g/kg/d in another animal produced an increase in F reticulocytes from 1 % to 21.6% and in HbF from 1.9% to 5.3%. Infusions in excess of 4 g/kg/d were complicated (after a variable amount of time) by a decreased level of alertness (caused by hyperosmolality or butyrate itself) and hematologic toxicity (with declines in reticulocyte, white blood cell, and platelet counts). Prolonged infusions of high doses of butyrate (8 to 10 g/kg/d) were associated with peak F reticulocyte percentages reaching 38% to 64.5% and HbF reaching levels in excess of 20%. These high doses (8 to 10 g/kg/d) were complicated in two animals with a striking and unique neuropathologic picture and, in one animal, multiorgan system failure. Erythropoietin in combination with butyrate, induced F reticulocytosis in an additive manner. We conclude that butyric acid is a strong inducer of HbF, particularly when administered in combination with erythropoietin. As chronic toxicities remain undefined, patients in future clinical trials of this and similar compounds should be monitored closely for evidence of neurologic toxicity.

The Effect of Erythropoietin in Combination with Radioprotective Agents on Erythropoietic Recovery and Survival in Irradiated Mice

The present study shows the effect of erythropoietin administered one hour post-irradiation on the erythropoietic recovery and survival of gamma-irradiated mice pretreated with a number of radioprotective agents and radioprotective mixtures. Both polycythemic and normal mice were used in these studies. Erythropoietin administered one hour post-irradiation to AET-protected mice produced more rapid erythropoietic recovery (as measured by blood and spleen59 Fe uptake) and better survival than in AET-protected mice which were not treated with erythropoietin. Doses of erythropoietin ranging from one to twenty units produced an equivalent effect. The erythropoietic recovery pattern of AET-protected mice given erythropoietin post-irradiation was studied to determine the effect of time (1 to 10 days) and increasing radiation exposure dose (700 to 1000 rads) on erythropoietic recovery using the radioiron technique. The possibility of further increasing erythropoietic recovery and survival in mice after irradiation...