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PubMed1986

Splenic erythropoiesis in rats under hypoxic and post-hypoxic conditions.

In rats chronic hypoxia causes extramedullary haematopoiesis mainly localized in the spleen. It is not known how splenic erythropoiesis develops and how it regresses after termination of hypoxia. In this study the spleen of rats exposed to chronic hypoxia was studied by light and electron microscopy; the findings were compared to relevant peripheral blood values. Splenic erythropoiesis begins almost immediately after exposure to hypoxia and reaches its maximum after 2-4 weeks. It occurs mainly in the splenic cords drawing upon local erythroblasts and is accompanied by an increase in splenic weight as well as a decrease in splenic iron stores. After termination of hypoxia marked phagocytosis by splenic cord macrophages diminishes the number of erythroblasts and of erythrocytes with a concomitant increase in splenic iron stores. Thus, splenic erythropoiesis appears to be inhibited as part of a rebound phenomenon and returned to normal by phagocytosis of erythroid cells within 4 weeks after cessation of the hypoxic stimulus.

Animals↗
PubMed1993

Myelodysplastic syndromes: immunohistochemical and morphometric evaluation of proliferative activity in erythropoiesis and endoreduplicative capacity of megakaryocytes.

An immunohistochemical and morphometric analysis was performed on bone marrow trephine biopsies in 40 patients with primary myelodysplastic syndromes (MDS) to evaluate the proliferative activity in erythropoiesis and the endoreduplicative capacity of megakaryocytes. Control groups included normal bone marrow and marrow from cases presenting with pernicious anaemia. Double-immunostaining was applied with a monoclonal antibody (PC10) directed against proliferating cell nuclear antigen (PCNA), followed by antibodies against glycophorin C (Ret40f) or platelet glycoprotein IIIa (Y2/51-CD61) for the identification of the erythroid and megakaryocytic cell lineage. Comparison with normal bone marrow showed a reduction of erythropoiesis accompanied by an increase in atypical (micro-) megakaryocytes. Erythroid precursors displayed significant enhancement of PCNA-immunostaining. Megakaryocytes showed no increase in the relative frequency of PC10-positive cells (PCNA-labelling index). In pernicious anaemia, predominance of macrocytic-megaloblastoid erythropoiesis was associated with a striking increase in PCNA-labelling. Cell kinetic studies in this disorder revealed an abnormal arrest, particularly in S-phase which generates an over-expression of PCNA. Similar conditions were believed to be present in MDS with secondary folate deficiency. This mechanism explains the relatively high rate of positively-reacting pro- and erythroblasts which is not invariably accompanied by an increase in cell proliferation. Determination of megakaryocyte size and PCNA-staining capacity resulted in a significant increase in PC10-positive cells among micromegakaryocytes. Our findings on this cell lineage are in keeping with the assumption of a block in endoreduplicative activity at higher ploidy levels, associated with an apparently not-deregulated endomitosis in small-sized megakaryocytes of lower ploidy stages.

Aged↗
PubMed1984

Systemic oxygen transport and erythropoiesis in the mouse.

Removal of 15% of blood volume in the mouse increases erythropoiesis by a factor of 2.2 when measured 12 h after bleeding. Exposure of normal mice to 40% reduced barometric pressure for the same period of time increases erythropoiesis only by a factor of 1.6. The response to hypoxia takes place in the presence of a 40% reduction of oxygen consumption and tissue-venous PO2, changes which are concomitant with a 5-fold increase in plasma erythropoietin activity. The larger response in anemic animals on the other hand occurs without any detectable change in these parameters. These results cast serious doubts about the interpretation of the quantitative homeostatic control of erythropoiesis based solely on the action of erythropoietin.

Anemia↗
PubMed1984

The toxic effects of heavy metals on rat bone marrow in vitro erythropoiesis: protective role of hemin and zinc.

The effects of gold (Au), lead (Pb), and cadmium (Cd) on rat bone marrow in vitro erythropoiesis (CFUE) were studied. Au was found to be significantly toxic to CFUE growth at concentrations as low as 10(-9) M whereas Pb and Cd displayed toxicity at 10(-7) M. Addition of Pb plus Cd in combination had a greater toxic effect on CFUE growth than when the metals were added singly, and the toxic effect of Cd was reduced when Zinc (Zn) was added in combination to the cultures. When hemin (10(-6) M) was added to cultures containing 10(-6) M Au, Pb, or Cd, CFUE numbers were obtained that were equivalent to control cultures without hemin. Thus, hemin exerted a protective effect on erythropoiesis in the presence of otherwise toxic amounts of Au, Pb, and Cd. It is concluded that Au, Pb, and Cd have toxic effects on in vitro erythropoiesis and that this toxicity may be overcome in part by Zn or hemin. The possible involvement of the heme biosynthetic and degradative pathways is discussed with respect to these results.

Animals↗
PubMed1992

Stimulating erythropoiesis increases complement receptor expression on primate erythrocytes.

Erythrocyte complement receptors (CR) are unique to primates and play a role in the clearance of immune complexes from the circulation. Immune complex-mediated diseases (e.g., systemic lupus erythematosus, SLE) cause decreased erythrocyte CR levels, resulting in decreased capacity of the erythrocytes to bind immune complexes that form in the circulation. Thus, raising erythrocyte CR levels might benefit patients with immune complex-mediated diseases. Because young erythrocytes express more CR than old erythrocytes, increasing erythropoiesis should increase the average number of CR expressed per erythrocyte. The present study was undertaken to test that hypothesis. Erythropoiesis was stimulated in nine cynomolgus monkeys (CYN) by weekly phlebotomy (30% of blood volume was removed, erythrocytes were discarded, and leukocytes were returned to the animal) for 8 weeks. Sham phlebotomy (30% of blood removed, then all components returned to the animal) was carried out weekly in four additional CYN for a period of 4 to 8 weeks. Sham phlebotomy did not change any of the parameters measured. However, phlebotomy resulted in a progressive increase in the mean number of CR expressed per erythrocyte (CR/erythrocyte): 2780 +/- 700 to 4230 +/- 820, P less than 0.0005. The increase in erythrocyte CR was first detected at about 2 weeks after the start of phlebotomy and was sustained through the course of phlebotomy. The increase in CR/erythrocyte included an increase in the percentage of erythrocyte expressing CR in clusters (37.9 +/- 6.4 vs 50.8 +/- 8.7%, P less than 0.01) as demonstrated by a flow cytometry study of the binding of fluorescent beads coated with anti-CR1 antibody. No significant change in leukocyte or platelet counts were observed. We conclude that stimulating erythropoiesis causes an increase in CR/erythrocyte. The magnitude of the increase suggests that it could be biologically significant.

Animals↗
PubMed1994

The role of cell fusion in erythropoiesis--Part 2.

In a prior study, cell fusion was found to play an important part in erythropoiesis in both the chicken and frog. Erythropoiesis in both organisms could be traced back to groups of embryonic cells which first fused to form an aggregate structure consisting of multiple nuclei enclosed by a common cytoplasm. The cytoplasm of the fused aggregate underwent dissolution to give rise to a set of denuded nuclei which, by manufacturing a haemoglobinized cytoplasm, were transformed into erythroblasts. Following these findings, the question of cell fusion in erythropoiesis in the human was investigated, and the results are reported here. Leishman stained smears of marrow aspirate were used, and care taken to prevent the immature cells coming into contact with plasma. The reason for this was that plasma was found to alter the normal structure of the immature haemopoietic cells, particularly the megakaryocyte series. Free from plasma contact, the nucleus of the megakaryocyte was found to be not multilobulated, but composed of a compact set of small nuclei. The mode of development of the megakaryocyte and its fate could be deciphered in the smears. The megakaryocytes arose as a result of fusion of small basophilic embryonic-like cells. After the megakaryocyte had attained a certain size, fusion ceased and the cytoplasm of the megakaryocyte underwent dissolution and was shed in the form of platelets, thus denuding the nuclei. The latter, bared of cytoplasm, were transformed directly into erythroblasts. The fate of the denuded nuclei in this manner goes against the accepted view that the denuded nucleus is phagocytosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Anemia and impaired stress-induced erythropoiesis in aceruloplasminemic mice.

Ceruloplasmin (Cp) is an abundant, copper-containing plasma protein with an important role in iron homeostasis. Patients with hereditary Cp deficiency have iron deposits in liver and other organs, consistent with impaired iron flux. The mild anemia reported in some patients suggests a possible role for Cp in iron delivery to red cell precursors during erythropoiesis. To investigate this function of Cp, we determined the hematologic parameters in Cp-deficient mice under normal conditions and after erythropoiesis-inducing stress. Cp(-/-) mice have below normal hematocrit, red cell hemoglobin and volume, and serum iron. Red cell number and turnover and reticulocyte counts were identical in Cp(-/-) and Cp(+/+) mice. Thus, Cp(-/-) have mild microcytic, hypochromic anemia consistent with normal red cell formation but defective iron availability. Cp(-/-) and Cp(+/+) mice subjected to phenylhydrazine-induced hemolytic anemia exhibited identical decreases in hematologic parameters, but Cp(-/-) mice showed diminished recovery after removal of the stress. Administration of purified human Cp or iron-saturated transferrin to Cp(-/-) mice partially restored hemoglobin formation in reticulocytes. The mild anemia in Cp(-/-) mice and the diminished response to stress may reflect inefficient recycling of iron between the reticuloendothelial and erythropoietic systems. Our findings suggest a role for Cp in erythropoiesis by providing sufficient iron to the erythroid tissue and that the requirement for Cp is raised after erythropoietic stress.

Anemia, Hypochromic↗
PubMed2004

Modulation of the expression and activity of cyclooxygenases in normal and accelerated erythropoiesis.

OBJECTIVE: The present study was aimed at characterizing the expression and activity of cyclooxygenase (COX) isoenzymes in erythropoiesis. METHODS: The expression and activity of cyclooxygenase (COX) and prostaglandin (PG) synthases were investigated in: 1) erythroblasts developed in culture from human CD34(+) hematopoietic progenitors, 2) erythroblasts in bone marrow specimens, and 3) peripheral erythrocytes isolated from healthy donors and from patients with a high regeneration rate of erythrocytes. RESULTS: While COX-1 protein was observed at each stage of erythroblast development, COX-2 protein was induced at later stages through a p38/MAPK-dependent pathway. Both COX isoforms were also observed in mature erythroblasts of the bone marrow. Erythroblasts developed in culture synthesized significantly more PGE(2) than TXB(2) and indomethacin delayed erythroid maturation. COX-1 and COX-2 were also observed in erythrocytes by immunostainings, although COX expression was confined to a fraction of circulating erythrocytes. Peripheral erythrocytes synthesized low but detectable amounts of PGE(2) and TXB(2). Similarly to erythroblast progenitors, PGE(2) was the prevalent prostanoid released by erythrocytes. This biosynthetic capacity was significantly increased in erythrocytes from patients with accelerated erythropoiesis as compared to controls. CONCLUSIONS: Both COX isoforms are present and enzymatically active during human erythropoiesis, although with different kinetics, and COX-derived prostanoids may play a role in erythroid maturation. Furthermore, peripheral erythrocytes retain in part the capacity of expressing COX and synthesizing prostanoids, which may contribute to the hemostatic/thrombotic response to vascular injury in different diseases, including congenital hemolytic disorders.

Adult↗
PubMed2005

Increased erythropoiesis in polycythemia vera is associated with increased erythroid progenitor proliferation and increased phosphorylation of Akt/PKB.

OBJECTIVE: The aim of this study was to explore the mechanism by which increased erythropoiesis occurs in polycythemia vera (PV). METHODS: CD34(+) and erythroid colony-forming cells (ECFC) were purified from normal or PV peripheral blood and then incubated in the presence of erythropoietin (EPO) to generate erythroid progenitor cells. Measurement of proliferation by Ki-67 staining, TUNEL assays to measure apoptosis, and Western blots for detection of Akt/PKB and glycogen synthase kinase 3 (GSK3) phosphorylation were performed in both normal and PV erythroid progenitors. RESULTS: Polycythemia vera erythroid progenitor cells generated 60% more cells compared to normal cells in liquid medium cell cultures. TUNEL assays revealed no difference between PV and normal erythroid progenitors, but Ki-67 staining for cell proliferation showed many more positive cells in the PV samples. A marked increase of phosphorylation of Akt/PKB occurred in the day-8 erythroid progenitors of 4/5 PV patients, compared to normal cells, after incubation with either stem cell factor (SCF) or EPO. PV cells also had much greater glycogen synthase kinase 3 (GSK3) alpha,beta phosphorylation compared to normal cells after incubation with SCF or EPO. These results are parallel to the cellular hypersensitivity of PV cells to SCF and EPO previously reported. CONCLUSIONS: Increased erythropoiesis in PV is associated with increased cellular proliferation and increased phosphorylation of Akt/PKB and GSK3. This study provides additional insight into the pathogenesis of PV and the regulation of normal erythropoiesis, even though a specific molecular defect of the disease is still not apparent.

Adult↗
PubMed2005

Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity.

OBJECTIVE: A deficiency of pyruvate kinase (PK) is the most common cause of hereditary nonspherocytic anemia due to glycolytic enzyme defects. Red cells are poorly deformable due to adenosine triphosphate depletion in individuals with a PK deficiency and are destroyed in the microcirculation of the reticuloendothelial system, leading to extravascular hemolysis. The pathophysiology of PK deficiency has been widely studied in PK-deficient mice (PK-1(slc)). We examined the effects of a PK deficiency on erythroid progenitor maturation using these mice. MATERIALS AND METHODS: The appearance of apoptotic cells in spleen of PK-1(slc) mice was examined by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) staining. We also assayed hematopoietic stem cell colony formation in vitro in the spleen of PK-1(slc) mice, to investigate erythropoiesis, and annexin V binding, as a measure of apoptotic cells in constitutive erythroid colonies, to evaluate the maturation of erythroid progenitors. RESULTS: The number of hematopoietic progenitors including colony-forming unit erythroids, burst-forming unit erythroids (BFU-E), colony-forming unit granulocyte-macrophages, and multilineage colony-forming units in the spleens of PK-1(slc) was remarkably increased indicating hematopoiesis, and enhanced erythropoiesis in particular. TUNEL assays identified apoptotic cells in the splenic red pulp of the PK-1(slc) mice. Two-color flow cytometry detected apoptotic cells among anti-TER119-positive cells, suggesting that apoptotic cells were of erythroid lineage. Cells undergoing apoptosis were detected in cultures of BFU-E generated from bone marrow cells of PK-1(slc) mice. CONCLUSIONS: The results in this study indicate that the metabolic disturbance in PK deficiency alters not only the survival of red cells but also the maturation of erythroid progenitors, resulting in ineffective erythropoiesis.

Animals↗
PubMed2003

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status.

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency.

Animals↗
PubMed1984

Inhibition of erythropoiesis in chronic renal failure: the role of parathyroid hormone.

Sera from 20 anemic patients with chronic renal failure (CFR) were studied for their effect on bone marrow in vitro erythroid colony formation (CFUE) and the observations correlated with parathyroid hormone (PTH) and ionized calcium levels in the patients' sera. Results demonstrated that 17 out of 20 patients' sera significantly inhibited in vitro erythropoiesis by 47% to 97%. No significant elevation in ionized calcium was found in 16 of the patients tested. Furthermore, assay of PTH levels in these patients revealed that 9 out of 20 had elevated levels of PTH. No correlation was found between PTH serum levels and the degree of in vitro inhibition of erythropoiesis (CFUE) by the patients' sera. Addition of up to 2,000 pg/mL (far above the patients' levels) of exogenous N-terminal or C-terminal PTH with in vitro bone marrow cultures resulted in no inhibitory effect on CFUE. It is concluded that the circulating inhibitor of erythropoiesis which has been shown to exist in the sera of this particular group of patients with CRF, is not PTH.

Adult↗
PubMed2000

Ineffective erythropoiesis in beta-thalassemia major is due to apoptosis at the polychromatophilic normoblast stage.

Beta-thalassemia major is characterized by ineffective erythropoiesis, although it is difficult to define the dynamics of this process from the static information revealed by analysis of bone marrow (BM) aspirates. We aimed to study the kinetics of sequential erythroid differentiation in beta-thalassemia major. We isolated the progenitor cells (CD34(+) and CD34(+)CD38(-) cells) from BM of thalassemia major patients and studied in vitro erythropoiesis. This is the first report of an in vitro study in human beta-thalassemia major from purified BM CD34(+) progenitor cells, using erythroid culture conditions, which allow unilineage differentiation to mature enucleated red blood cells. In contrast to normal donors, a high proportion of BM CD34(+) and CD34(+)CD38(-) progenitors from beta-thalassemia major coexpressed the late erythroid lineage-specific protein glycophorin A and generated a higher proportion of erythroid colonies. However, despite the marked increase in erythroid clonogenicity of the progenitor population, erythroid cultures initiated from beta-thalassemia major BM CD34(+) cells expanded 10- to 20-fold less than from normal BM. There were less viable cells during differentiation, specifically after the polychromatophilic normoblast stage. There was a progressive increase in the apoptotic erythroid progeny with differentiation, and apoptosis occurred predominantly at the polychromatophilic normoblast stage. In thalassemia major, BM progenitor cells show increased erythroid clonogenicity, increased expression of late erythroid lineage-specific proteins, and accelerated erythroid differentiation. However, despite the apparent increased erythroid commitment, ineffective erythropoiesis occurs due to apoptosis at the polychromatophil stage. Identification of the differentiation stage at which apoptosis occurs will permit further studies of the underlying mechanisms and target therapeutic strategies to improve red cell production.

ADP-ribosyl Cyclase↗
PubMed1999

Modulation of erythropoiesis in rat bone marrow erythroblastic islands by cyclooxygenase inhibition.

We designed our study to explore how the inhibition of prostaglandins (PGs) could affect erythropoiesis in bone marrow erythroblastic islands (EIs). To this end, we used hypoxic-stimulated rats-hypobaric hypoxia (42.55 kPa/6 h)-pretreated or not with indomethacin (4 mg/kg/3 days). Blood sampling was done at 0 h, 24 h, and 72 h after hypoxia. The study included estimations of the plasma erythropoietin (EPO) level (by radioimmunoassay), peripheral blood, number of EI from classes I to V per femur, rate of immature cell's differentiation into erythroblasts, and rate of repeated participation of macrophages in new EI reconstruction. Plasma EPO rose significantly (p < 0.01) in all hypoxic rats: 40.5+/-10.15 mU/ml and 46.75+/-16.28 mU/ml and at 0 h versus 13.83+/-6.82 mU/ml in controls. An increased rate of cell differentiation into erythroblasts in EIs (p < 0.01), an enhanced reconstruction in involuted EIs, and a reduced number of maturing EIs (p < 0.01) were observed in all hypoxic animals. However, in indomethacin-pretreated rats, the stimulation of bone marrow erythropoiesis was better expressed. Our results favor the concept that PG inhibition does not attenuate the erythropoietic response to hypoxia and support the hypothesis about the important role of EI macrophages as a local regulator of bone marrow erythropoiesis.

Animals↗
PubMed2002

Mechanisms underling the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation.

We studied the effects of adaptogens extracts of Siberian ginseng, Rhodiola rosea, bergenia, and ginseng and pantohematogen, on erythropoiesis after paradoxical sleep deprivation. Adaptogens stimulated bone marrow erythropoiesis in the early stage, but decreased the count of bone marrow erythrokaryocytes 3-7 days after treatment. The effect of adaptogens on erythropoiesis is associated with modulation of the state of brain neurotransmitter systems followed by changes in functional activity of cells in the hemopoiesis-inducing microenvironment.

Animals↗
PubMed1994

Erythropoiesis after withdrawal of enalapril in post-transplant erythrocytosis.

Enalapril effectively decreases hematocrits in patients with postrenal transplant erythrocytosis (PTE). We studied the effect of enalapril withdrawal on erythropoiesis in 18 patients with PTE who had been treated for 13 +/- 8 months. Hematocrit, reticulocyte count, plasma erythropoietin, and plasma insulin-like growth factor I were measured biweekly for six weeks. Red cell mass, plasma volume, transferrin saturation, and plasma angiotensin II were measured at withdrawal and six weeks later. Hematocrit increased by at least 0.04 in 13 patients ('responders') but changed by -0.08 to 0.01 in five patients ('nonresponders'). In the responder subgroup, hematocrit increased from 0.43 +/- 0.05 to 0.51 +/- 0.05 (P < 0.001), red cell mass increased from 25.4 +/- 5.9 to 28.9 +/- 5.9 ml/kg body weight (P < 0.001), and transferrin saturation decreased from 41 +/- 16 to 27 +/- 9 percent (P < 0.01). Reticulocyte count increased two weeks after withdrawal of enalapril. Plasma volume did not change significantly. No measurement changed in the nonresponder subgroup. Plasma levels of erythropoietin, total erythroid stimulating activity, insulin-like growth factor I, and angiotensin II did not change significantly in either subgroup. Enalaprilat did not inhibit erythropoiesis in cell culture. Thus, erythropoiesis increased in 13 of 18 patients after stopping enalapril and was independent of changes in circulating concentrations of several erythropoietic factors, including erythropoietin. The pathogenesis of PTE and mechanism underlying the beneficial effect of angiotensin converting enzyme inhibition remain undetermined.

Blood Proteins↗
PubMed2004

The Rb tumor suppressor is required for stress erythropoiesis.

The retinoblastoma tumor suppressor gene plays important roles in cell cycle control, differentiation and survival during development and is functionally inactivated in most human cancers. Early studies using gene targeting in mice suggested a critical role for pRb in erythropoiesis, while more recent experiments have suggested that many of the abnormal embryonic phenotypes in the Rb null mouse result from a defective placenta. To address this controversy and determine whether Rb has cell intrinsic functions in erythropoiesis, we examined the effects of Rb loss on red cell production following acute deletion of pRb in vitro and under different stress conditions in vivo. Under stress conditions, pRb was required to regulate erythroblast expansion and promote red cell enucleation. Acute deletion of Rb in vitro induced erythroid cell cycle and differentiation defects similar to those observed in vivo. These results demonstrate a cell intrinsic role for pRb in stress erythropoiesis and hematopoietic homeostasis that has relevance for human diseases.

Anemia, Aplastic↗
PubMed1998

Characterization of the erythropoiesis in myelodysplasia by means of ferrokinetic studies, in vitro erythroid colony formation and soluble transferrin receptor.

In refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) a discrepancy is observed between the decreased in vitro erythroid colony formation and the normal or increased number of normoblasts in the bone marrow. To study the in vivo and in vitro erythropoiesis in more detail erythron transferrin uptake (ETU), soluble transferrin receptor (sTfR) and erythroid in vitro colony formation were performed in 24 patients with RA and five patients with RARS. These results were correlated with bone marrow morphology and transfusion dependency. Increased (mean, 124.9; range, 74-225 micromol/l blood/day) and normal (mean, 60.6; range, 50-71) ETU values were observed in 51% and 28% of the cases, whereas 21% of the cases demonstrated a diminished ETU value (mean, 35.8; range, 28-46), which correlated significantly with sTfR in cases with RA (P < 0.05, r = 0.64). A significant difference in ETU values was observed between RA (mean, 77.6; range, 28-189) and RARS (mean, 144.0; range, 59-225, P < 0.05). Most of the cases (73%) with increased ETU values showed an augmented percentage of erythroblasts in the bone marrow, which was inversely related with the serum Epo levels (P < 0.05, r = 0.51). However no correlation was found between the ETU values and the in vitro erythroid colony formation. Transfusion dependency was associated with normal to increased ETU levels (P < 0.05) and cytogenetic abnormalities (P < 0.05). These observations demonstrate that different patterns of defects can be observed in the erythropoiesis of RA and RARS patients whereby normal to increased ETU levels and the presence of cytogenetic abnormalities differentiate between cases of RA with ineffective erythropoiesis associated with regular transfusions and cases who are relatively transfusion independent.

Adult↗