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PubMed2005

Lyn deficiency reduces GATA-1, EKLF and STAT5, and induces extramedullary stress erythropoiesis.

In vitro studies have implicated the Lyn tyrosine kinase in erythropoietin signaling. In this study, we show that J2E erythroid cells lacking Lyn have impaired signaling and reduced levels of transcription factors STAT5a, EKLF and GATA-1. Since mice lacking STAT5, EKLF or GATA-1 have red cell abnormalities, this study also examined the erythroid compartment of Lyn(-/-) mice. Significantly, STAT5, EKLF and GATA-1 levels were appreciably lower in Lyn(-/-) erythroblasts, and the phenotype of Lyn(-/-) animals was remarkably similar to GATA-1(low) animals. Although young adult Lyn-deficient mice had normal hematocrits, older mice developed anemia. Grossly enlarged erythroblasts and florid erythrophagocytosis were detected in the bone marrow of mice lacking Lyn. Markedly elevated erythroid progenitors and precursor levels were observed in the spleens, but not bone marrow, of Lyn(-/-) animals indicating that extramedullary erythropoiesis was occurring. These data indicate that Lyn(-/-) mice display extramedullary stress erythropoiesis to compensate for intrinsic and extrinsic erythroid defects.

Animals↗

PubMed2000

Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?

INTRODUCTION: Iron overload is usually observed in patients (even untransfused) with myelodysplastic syndromes (MDS), and contributes towards the generation of low molecular weight iron complexes or non-transferrin-bound iron (NTBI), which in turn favors oxidative DNA damage and consequent apoptosis. MATERIALS AND METHODS: Levels of NTBI and lipid peroxidation were evaluated by means of free serum malondyaldehyde (MDA) in untransfused MDS patients and we tried to correlate them with ineffective erythropoiesis, apoptosis and the pattern of in vitro growth. RESULTS: NTBI levels were found to be significantly higher in low-risk than in high-risk MDS patients, as well as in patients with a lower myeloid/erythroid ratio. MDA was found to be uniformly higher in the MDS patients as a whole than in normal controls. The bone marrow progenitor cells in the MDS patients with high NTBI levels showed a higher degree of apoptosis, but this difference was not statistically significant. Patients with a leukemic growth pattern had lower NTBI levels than those with a non-leukemic pattern. CONCLUSION: These data suggest that NTBI is related to the degree of ineffective erythropoiesis and that it contributes towards inducing apoptosis in MDS bone marrow precursors. The presence of leukemic growth is associated with low NTBI levels, probably due to increased iron consumption by blast cells.

Apoptosis↗

PubMed1997

Recombinant human thrombopoietin (TPO) stimulates erythropoiesis by inhibiting erythroid progenitor cell apoptosis.

Thrombopoietin (TPO) has been reported to stimulate erythropoiesis, but the stimulatory mechanism has not been defined. To address this issue, we performed serum-free cell-culture experiments with recombinant human TPO and purified human progenitor cells. We found that TPO alone was able to stimulate the megakaryocyte colony formation in serum-free cultures, but erythroid colonies were never observed. Only in the presence of EPO (erythropoietin) +IL-3 was TPO able to stimulate a small increase (approximately 25%) in erythroid colony formation. Accordingly, we hypothesized that TPO might have an effect on erythroid progenitor cell viability, rather than a direct stimulatory effect. To test this idea, CD34+ cells were cultured for 7d in serum-free methylcellulose in the presence or absence of TPO, after which time KL+ EPO was added to the cultures. Cells which were pre-cultured for 7 d in the presence of TPO gave rise to approximately 6 times as many burst forming unit-erythroid (BFU-E) colonies as cells which were pre-cultured in the absence of TPO. Further, when primitive CD34+, Kit+ MNC were cultured for 3-7 d under serum-free conditions in the presence or absence of TPO, significantly fewer cells cultured in the presence of TPO displayed apoptotic changes when compared to cells cultured in the absence of TPO. Taken together, these results suggest that TPO has little direct stimulatory effect on erythroid progenitor cells, but might indirectly enhance erythropoiesis by preventing very early erythroid progenitor cells from undergoing apoptotic cell death.

Apoptosis↗

PubMed1997

Murine endothelial cells support fetal liver erythropoiesis and myelopoiesis via distinct interactions.

Endothelial cells are an important component of the haemopoietic microenvironment. To investigate how endothelial cells are involved in haemopoiesis, two established murine endothelial cell lines were assayed in stromal cultures with fetal liver haemopoietic cells. Both endothelial cell lines allowed for the proliferation and differentiation of erythroid and monocyte-macrophage precursors, suggesting that support for haemopoiesis is a general property of endothelial cells. Erythropoiesis was dependent on the addition of erythropoietin (Epo), whereas myelopoiesis was independent of added Epo. Haemopoietic colonies developed in close contact with the endothelial cells. Erythroid colonies did not develop when transwell filters were used between the stroma and haemopoietic cells, or when conditioned medium was used in place of stromal cells. In contrast, monocyte-macrophage colonies formed in the presence of transwell filters or conditioned medium. Thus close cell contact is necessary for erythropoiesis but not myelopoiesis under these conditions. These results suggest that different molecular mechanisms are used by endothelial cells to support erythroid development and myeloid development in the mouse fetal liver.

Animals↗

PubMed1999

Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction.

Ineffective erythropoiesis in myelodysplasia is characterized by a defect in erythroid progenitor growth and by abnormal erythroid differentiation. Increased apoptosis of erythroid, granulocytic and megakaryocytic lineages is thought to account for cytopenias. Erythropoietin (Epo)-induced BFU-E and CFU-E growth was studied in 25 myelodysplastic syndrome (MDS) marrow specimens and found to be drastically diminished. To investigate the functionality of Epo-R in MDS marrow, we focused on Epo-induced STAT5 activation. Epo was able to stimulate STAT5 DNA binding activity in all normal and 12/24 MDS marrows tested, with no correlation between the level of STAT5 activation and the development of erythroid colonies in response to Epo. In contrast, impaired proliferation of erythroid progenitors was related to an increased expression of the transmembrane mediator of apoptotic cell death Fas/CD95 on the glycophorin A+ subpopulation. Therefore we conclude that the stimulation of pro-apoptotic signals rather than the defect of anti-apoptotic pathways resulting from Epo-stimulated Jak2-STAT5 pathway, predominantly accounts for ineffective erythropoiesis in myelodysplasia.

Adult↗

PubMed2001

A systematic approach to the assessment of erythropoiesis.

The pathogenesis of anaemia may be simple or complex and the differential diagnosis can be difficult. An appreciation of the erythropoietic processes is required, together with regular review of investigations, to ensure that appropriate protocols are adopted. The application of tests, which define different facets of erythropoiesis, should be appropriate to the clinical circumstances. In some situations, such as the anaemia of chronic disorders, pregnancy and chronic renal failure, a detailed analysis of erythropoiesis is often required. Guidelines for investigating anaemia due to megaloblastosis or haemoglobinopathy are well established, whereas disturbances of iron metabolism are often difficult to classify. These require a clear distinction between storage and functional iron to differentiate whether the defect is due to readily treatable simple iron deficiency or more complex mechanisms, which do not respond to iron supplementation. Determination of red cell haemoglobin content, reticulocyte analysis and the assay of serum transferrin receptors are new generation parameters developed to address this. Practice pressures and new treatment options have contributed to investigations becoming more complex, especially those of the secondary anaemias, as new tests have become more readily available and often automated. This has resulted in reduced turnaround times and clinical demand has driven request patterns. Initiatives to develop evidence-based anaemia management protocols are welcomed but, wherever possible, should be developed through collaboration between the haematology department and the user unit, and based on available guidelines.

Anemia↗

PubMed2000

Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with postpartum anaemia and blunted erythropoiesis.

BACKGROUND: To compare efficacy between recombinant human erythropoietin (rhEPO) plus parenteral iron vs. iron alone (parenteral vs. oral) in postpartum anaemia. METHODS: Sixty patients (haemoglobin 8.6 +/- 1.1 g dL-1) were randomized to rhEPO plus intravenous (i.v.) iron sucrose (group 1), rhEPO placebo plus i.v. iron sucrose (group 2), or oral iron alone (group 3), daily for 4 days beginning 48-72 h postpartum. Erythropoiesis and iron status were assessed before, and on 4, 7 and 14 days after, starting therapy. RESULTS: On day 7 the group 1 haematocrit increase was 7.7 +/- 3.1% vs. 5.3 +/- 1.9% (group 2, P < 0.01) and 4.4 +/- 3.2% (group 3, P < 0.01), and on day 14, 11.3 +/- 2.9% vs. 9.2 +/- 3.4% (group 2, P < 0.05) and 8 +/- 2.8% (group 3, P < 0.01). The odds of achieving a target haematocrit > 32% on day 7 and > 35% on day 14 were higher on rhEPO (1.5-2.7) than on either iron regimen alone. Group 1 reticulocyte counts were also higher on days 4 (P < 0.05 vs. oral iron) and 7 (P < 0.01 vs. oral and parenteral iron). CONCLUSION: All three regimens were effective in postpartum anaemia, but the haematocrit and reticulocyte responses to rhEPO plus parenteral iron were significantly greater than to iron alone. Benefit was greatest in the blunted erythropoiesis subgroup with elevated post-Caesarean section C-reactive protein levels.

Anemia↗

PubMed1999

Characterization and expression of embryonic globin in the rainbow trout, Oncorhynchus mykiss: intra-embryonic initiation of erythropoiesis.

When fractionated by reverse-phase high performance liquid chromatography (HPLC), the embryonic hemoglobin of the rainbow trout, Oncorhynchus mykiss, consisted of eight globins different from adult globins in terms of retention time. Amino acid sequences of the N-terminal regions of some globins were determined. In addition, four cDNA clones for embryonic globins from 10-day embryos were isolated (at 15 degrees C), sequenced and the amino acid sequences predicted. In comparison with the sequences of previously characterized globins, they corresponded to two alpha-type and two beta-type globins and therefore were named em.alpha-1, em.alpha-2, em.beta-1 and em.beta-2. The N-terminal 36 amino acids of one (E2) of the embryonic globins isolated by HPLC were identical to those of the sequence deduced from a cDNA, em.beta-2. The phylogenetic relationship between the embryonic globins and other globins previously reported was discussed. The present study is the first demonstration of amino acid sequences of embryonic globins in a teleost. To understand the initiation of erythropoiesis in the early development of the rainbow trout, histochemistry using o-dianisidine/hydrogen peroxide, immunohistochemistry using an antibody against embryonic hemoglobin, and northern blotting and whole embryo in situ hybridization using antisense RNA probe for em.beta-2 were performed. Embryonic globin mRNA, globin and hemoglobin appeared first in the anterior part of the intermediate cell mass (ICM) located in the median line beneath the notochord of embryos 6-7 days after fertilization at 15 degrees C (Vernier's stages 16-20). Shortly after that, the expression signal extended to the posterior part of the ICM and spread out laterally to blood islands on the posterior yolk sac. Thus, the initiation of erythropoiesis in the early embryo of rainbow trout is intraembryonic.

Amino Acid Sequence↗

PubMed1999

Role of the macrophage in erythropoiesis.

Macrophages, which are derived from precursor cells in the bone marrow, differentiate specifically under the influence of the local microenvironment. Resident macrophages in hematopoietic tissues can be distinguished from other stromal cells and monocytes by immunostaining with monoclonal antibody F4/80 and anti-Forssman glycosphingolipid antibody, respectively. Erythroid colony-forming units adhere to a resident macrophage and differentiate to erythroblasts in the presence of erythropoietin (EPO), resulting in the formation of an erythroblastic island. Resident macrophages play a supportive role in erythropoiesis, probably by preventing apoptosis of the erythroid precursors via adhesive interaction between very late activation antigen 4 and vascular cell adhesion molecule 1. Herein is proposed a model of erythropoiesis based on cooperative interaction between EPO and resident macrophages.

Animals↗

PubMed1992

The effect of oral iron supplementation on erythropoiesis in autologous blood donors.

The effect of oral iron supplementation on erythropoiesis was studied prospectively in 34 autologous blood donors. The subjects, all of whom were to undergo total hip surgery, had normal iron status at the start of the study. During the preoperative period, in which 4 units of blood were collected, 17 patients received oral iron supplementation with 287 mg of ferrous sulfate (105 mg of elemental iron/day), while 17 patients did not use any iron supplementation. Oral iron supplementation during the 4-week preoperative period lessened the decrease in ferritin levels after two phlebotomies. Neither the decrease in hemoglobin nor the increase in erythropoietin levels was influenced by iron supplementation. In both iron-supplemented and control patients, serum erythropoietin levels returned to initial values within a few days after surgery. In autologous blood donors with a normal iron status, the use of supplemental iron does not affect erythropoiesis and is insufficient to maintain iron stores.

Administration, Oral↗

PubMed1997

A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis.

BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta-thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/- 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/- 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements decreased from 137 +/- 26 to 104 +/- 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/- 1515 to 1187 +/- 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis.

Adolescent↗

PubMed2001

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy.

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(-1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.

Adult↗

PubMed2001

Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer.

Anaemia is a common haematologic disorder in patients with cancer and has a multifactorial aetiology, including the effects of the malignancy itself and residual effects from previous therapy. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa), a protein with additional sialic acid compared with erythropoietin (EPO), stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO) but it is biochemically distinct. NESP, with its approximately 3-fold greater serum half-life, can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure and do so with less frequent dosing. We investigated the ability of NESP to safely increase haemoglobin levels of anaemic patients with non-myeloid malignancies not receiving chemotherapy. NESP was administered under the supervision of a physician at doses of 0.5, 1.0, 2.25 or 4.5 mcg kg(-1)wk(-1)for a maximum of 12 weeks. This report includes 89 patients completing the study by November 2000. NESP was well tolerated, with no reported dose-limiting toxicities or treatment-related severe adverse events. Increasing doses of NESP corresponded with increased efficacy. The percentage (95% confidence interval) of patients responding ranged from 61% (42%, 77%) in the 1.0 mcg kg(-1)wk(-1)group to 83% (65%, 94%) in the 4.5 mcg kg(-1)wk(-1)group.

Adult↗

PubMed2004

Sustained swimming increases erythrocyte MCT1 during erythropoiesis and ability to regulate pH homeostasis in rat.

We investigated the effect of sustained swimming exercise on the increase in monocarboxylate transporter 1 (MCT1) concentration and its ability to regulate pH homeostasis in rat erythrocytes. Male Sprague-Dawley rats aged 9 weeks were divided into sedentary and swimming groups for both 1- and 3-week experiments. The exercise group swam for 30 - 60 min/day, 5 days/week. Before and 1 and 3 weeks after initiation of the exercise, blood was collected for lactate concentration measurement during pre-exercise rest and post-exercise recovery periods. On the last day of each experiment, venous blood and erythroid cells in bone marrow were collected to assay the capacity for erythropoiesis and MCT1 concentration. In the swimming group at 0 weeks (p < 0.05), 1 week (p < 0.01) and 3 weeks (p < 0.001), the blood lactate concentration post-exercise was significantly higher than at rest. The ratio of young erythrocytes to total erythrocytes was significantly higher in the 3-week swimming group than in the sedentary group (p < 0.05). The MCT1 concentration in erythrocytes was higher in the 3-week swimming group than in the sedentary group (18 %, p < 0.05), which was found in young erythrocytes (22 %, p < 0.05) when total erythrocytes were separated into young and old fractions. The MCT1 concentration in erythroid cells was higher in both the 1-week and 3-week swimming groups than in either of the sedentary groups (27 and 28 %, respectively, p < 0.05). The pH recovery of erythrocyte suspensions at 10, 15 and 20 seconds after addition of lactate to the suspension medium was significantly faster in the 3-week swimming group than in the sedentary group (p < 0.001). These findings suggest that erythrocyte MCT1 is increased during erythropoiesis in bone marrow and that the increase of the transporter facilitates, at least partly, lactate/proton co-transport due to sustained swimming exercise in rats.

Acid-Base Equilibrium↗

PubMed2006

The role of JAK2 V617F mutation, spontaneous erythropoiesis and megakaryocytopoiesis, hypersensitive platelets, activated leukocytes, and endothelial cells in the etiology of thrombotic manifestations in polycythemia vera and essential thrombocythemia.

Exaggerated erythropoiesis and megakaryocytopoiesis are present at a variable extent in polycythemia vera (PV) and essential thrombocythemia (ET). With the recent discovery of the V617F mutation in the Janus kinase 2 (JAK2) tyrosine kinase in almost all cases of PV and in a subset of patients with ET, studies are now pending to assess the role of this mutation in the hematopoietic cell activation process and/or in the occurrence of thromboses in ET and PV. The JAK2 V617F point mutation makes the normal hematopoietic progenitor cells hypersensitive to thrombopoietin, erythropoietin, and myeloid progenitor cells, leading to trilinear hematopoietic myeloproliferation. This will have three main clinical consequences during long-term follow-up. First, spontaneous growth of enlarged mature megakaryocytes in ET/PV with overproduction of hypersensitive platelets results in a broad spectrum of platelet-mediated microvascular circulatory disturbances, which are very sensitive to low-dose aspirin. Second, spontaneous growth of erythropoiesis with the overproduction of erythrocytes leads to classic PV with increased hemoglobin, hematocrit, and red cell mass. This is associated with a high frequency of major arterial and venous thrombotic complications in addition to platelet-mediated microvascular circulatory disturbances of thrombocythemia. Third, the slowly progressive myeloid (granulocytic) metaplasia in bone marrow and spleen is complicated by secondary myelofibrosis caused by a megakaryocytic/granulocytic cytokine storm in about one fourth to one third of JAK2 V617F-positive PV patients after long-term follow-up, with no tendency of leukemic transformation as long as they are not treated with myelosuppressive agents. Randomized clinical trials directly comparing phlebotomy versus hydroxyurea or interferon alpha versus hydroxyurea in PV with progressive disease are lacking. Heterozygous V617F mutation is enough to produce the clinical picture of ET with a slight tendency to increased hemoglobin and hematocrit (early PV mimicking ET). Homozygous V617F mutation is associated with the clinical picture of classic PV and with a higher tendency to secondary myelofibrosis, but with no increased leukemia unless other biological or genetic factors come into play, such as myelosuppressive agents or the acquisition of additional biologic or genetic defects. Depending on the biological background of individual patients, heterozygous and homozygous JAK2 V617F ET/PV may preferentially induce myeloid metaplasia with myelofibrosis with a relative suppression of megakaryocytic and erythropoietic myeloproliferation leading to clinical pictures of fibrotic chronic idiopathic myelofibrosis (CIMF) or agnogenic myeloid metaplasia. The main conclusion is that JAK2 V617F is a 100% specific clue to a new distinct clonal myeloproliferative disorder. JAK2 V617F-positive ET/PV and CIMF should be distinguished from wild-type JAK2 ET, rare cases of PV, and CIMF, and should be evaluated during life-long follow-up.

Blood Platelets↗

PubMed1984

Effects of oxygen inhalation on endogenous erythropoietin kinetics, erythropoiesis, and properties of blood cells in sickle-cell anemia.

The role of oxygen therapy in sickle-cell anemia is not established, and its effects on erythropoiesis and on the rheologic properties of sickled erythrocytes are controversial. When three patients with sickle-cell anemia who were not in crisis or infected breathed oxygen at a rate of 5 liters per minute continuously through nasal prongs for five days, there was a rapid decline in erythropoietin levels that had initially been elevated, a delayed fall in the number of reticulocytes, and a fall in the number of irreversibly sickled cells, which, in two of the subjects, preceded the suppression of reticulocytosis. After cessation of oxygen therapy, erythropoietin levels and the number of irreversibly sickled cells increased promptly, followed by an increase in the number of reticulocytes. Calculated erythropoietin half-lives were 1.51 to 2.92 hours, and clearances were 43 to 84 ml per minute during oxygen administration. These are normal values. In two subjects, the number of irreversibly sickled cells rose to exceed base-line values after oxygen therapy was discontinued, and both subjects had acute painful episodes at this time. We conclude that in patients with sickle-cell anemia, substantial changes in erythropoiesis and in the rheologic properties of blood occur in association with oxygen inhalation and that when oxygen therapy is administered to such patients, it should be given intermittently rather than continuously.

Anemia, Sickle Cell↗

PubMed2003

Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates.

OBJECTIVES: Human fetuses and neonates ingest erythropoietin (Epo) when they swallow amniotic fluid, colostrum, and human milk. This study was designed to determine whether enterally dosed recombinant Epo (rEpo) stimulates erythropoiesis in preterm neonates. METHODS: Preterm infants (<1500 g birth weight) were randomly assigned to receive feedings supplemented with either rEpo (1000 U/kg per day) or placebo for 14 days (n=36). Reticulocyte counts, serum Epo concentrations, hematocrit, and zinc protoporphyrin to heme ratios were measured at baseline and after 7 and 14 days of study drug administration. Transfusion guidelines were followed. Transfusion requirements, medications, feeding tolerance, and clinical diagnoses were documented. RESULTS: Enteral rEpo was well tolerated. There were no differences in erythropoietic indexes based on treatment group. Serum Epo concentrations were not different in the treatment versus placebo group, nor were transfusion requirements. CONCLUSIONS: Enterally dosed rEpo (1000 U/kg/day) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period, nor does it elevate the serum Epo concentration in preterm or term infants. Oral administration of rEpo is not an effective substitute for parenteral administration.

Administration, Oral↗

PubMed2002

The synergistic effect of thrombopoietin in erythropoiesis with erythropoietin and/or IL-3 and myelopoiesis with G-CSF or IL-3 from umbilical cord blood cells of premature neonates.

The authors sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with other cytokine(s) on burst-forming unit-erythroid (BFU-E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony formations from cord blood of premature neonates. Cord blood nonadherent mononuclear cells (MNC) from normal premature neonates were cultured in a methylcellulose system. When cultured with 1 x 10(4) MNC/mL, erythropoietin (EPO) 2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 100 ng/mL, the addition of TPO to EPO gave rise to more BFU-E-derived colonies (p = .000). The addition of TPO to EPO + IL-3 gave rise to more BFU-E-derived colonies (p = .002) also. TPO synergizes erythropoiesis from cord blood of premature neonates. Likewise, the addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies (p = .000) also. TPO synergizes myelopoiesis from cord blood of premature neonates. Thus, TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord blood of premature neonates.

Cells, Cultured↗