losartan-potassium and Anemia--Megaloblastic

Haematological abnormalities are common in systemic lupus erythematosus (SLE) and may be manifested by anaemia of different pathogenesis. The objective of this article was to describe some data concerning autoimmune haemolytic anaemia, aplastic and megaloblastic ones accompanying SLE and also to present erythropoietin (EPO) function in the above mentioned diseases. In SLE many factors are produced which disturb the organism haematological balance both on the peripheral level and in the bone marrow. It is assumed that the autoantibodies produced in SLE are the main cause of anaemia. However it should be considered that quantitative changes in the number of erythrocytes observed in this disease are also caused by chronic inflammatory condition, which as the element of autoimmune disease impairs the endocrine function of the kidneys in EPO production. It influences bone marrow, iron metabolism and then haemopoiesis. Apart from humoral factors the role of mechanisms connected with immune cellular response is also considered.

Topics: Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Anemia, Megaloblastic; Erythropoietin; Humans; Immunity, Cellular; Kidney; Lupus Erythematosus, Systemic

Automated counting of reticulocytes has markedly increased the precision and accuracy of this assay compared with the traditional manual counts. In addition, several new reticulocyte parameters are now available to clinicians and pathologists. This review examines the potential role of these parameters in the diagnosis and management of anemias. Reticulocyte maturity can now be assessed based on the staining intensity of reticulocytes, which is proportional to their RNA content. However, the clinical value of the numerical estimate of the immature reticulocyte fraction has not been yet demonstrated. In the bone marrow transplant setting, there is no clear evidence that the use of this index results in improved care of these patients, and many studies have failed to show its superiority compared with the traditional white cell count, especially for autologous transplants. Direct measurement of reticulocyte volume, hemoglobin concentration, and hemoglobin content are now available. Studies have shown that these parameters, and hemoglobin content in particular, allow a real-time assessment of the functional state of the erythroid marrow. In the setting of recombinant human erythropoietin therapy, studies of hemoglobin content have shown that this index allows an early detection of functional iron deficiency. Preliminary studies have also shown that this index may be helpful in the diagnosis of iron deficiency and in the monitoring of iron replacement therapy.

Topics: Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Sickle Cell; Bone Marrow; Bone Marrow Diseases; Bone Marrow Transplantation; Cell Size; Cellular Senescence; Erythropoietin; Graft Survival; Hematologic Diseases; Hemoglobins; Humans; Iron Deficiencies; Recombinant Proteins; Reference Values; Reticulocyte Count; Reticulocytes; RNA; Staining and Labeling

In summary, anemia developing in a patient with cancer can be due to several different factors. A relative failure of erythropoiesis, in conjunction with a modestly shortened erythrocyte survival, is the most likely explanation for the anemia and can occur in patients with or without bone marrow invasion. Several theories have been proposed to explain the mechanism of limited red cell production in cancer. Internal iron starvation and cancer toxic factors have been widely implicated. Immunoglobulin inhibitors of erythropoiesis occur in the rare entity, pure red cell aplasia, which is sometimes associated with thymomas. Autoimmune hemolytic anemia and microangiopathic hemolytic anemia can also occur in patients with solid cancers, pointing out the need for a complete evaluation of anemia in any patient with recent-onset anemia. Successful treatment and prognostic implications of anemia in cancer is dependent on proper diagnosis.

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Megaloblastic; Anemia, Myelophthisic; Bone Marrow; Erythropoiesis; Erythropoietin; Humans; Intestinal Absorption; Iron; Mononuclear Phagocyte System; Neoplasms

Topics: Adolescent; Adult; Anemia; Anemia, Hypochromic; Anemia, Megaloblastic; Animals; Child; Child, Preschool; Dapsone; Drug Combinations; Erythropoietin; Female; Hookworm Infections; Humans; Infant; Iron-Dextran Complex; Leishmaniasis, Visceral; Macaca mulatta; Malaria; Male; Mice; Middle Aged; Protein-Energy Malnutrition; Pyrimethamine; Schistosomiasis; Socioeconomic Factors; Tropical Medicine; Trypanosomiasis, African

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Megaloblastic; Danazol; Erythropoietin; Humans; Male; Recombinant Proteins

In rats, in contrast with human subjects who develop megaloblastic anaemia due to vitamin B12 deficiency, haematological abnormalities with anaemia were not observed under normoxic conditions even though plasma vitamin B12 concentration was reduced to <15 % of a normal concentration by depleting dietary vitamin B12. To elucidate whether erythropoiesis was affected by vitamin B12 deficiency in rats, these vitamin B12-deficient rats were exposed to hypoxia (10.5 % O2) to stimulate erythropoiesis. In the vitamin B12-sufficient control rats, erythrocyte count was significantly (P<0.05) increased 1 week after starting the hypoxic exposure. However, the hypoxia-induced erythropoiesis was affected by vitamin B12 deficiency, and no significant increase in the erythrocyte count was observed even after 6-week exposure to hypoxia in the vitamin B12-deficient rats. In the vitamin B12-deficient rats in hypoxia, erythrocytes became abnormally enlarged, and haemoglobin concentration in peripheral blood was increased in proportion to the increase of mean corpuscular volume. However, the level of the increase in the haemoglobin concentration was significantly (P<0.05) lower in the vitamin B12-deficient rats compared with that in the -sufficient controls. In addition, in the vitamin B12-deficient rats, in contrast to the -sufficient rats, serum erythropoietin concentration was not normalized even after 6-week exposure to hypoxia. These results indicate that a megaloblastic anaemia-like symptom is induced when the vitamin B12-deficient rats are exposed to hypoxia.

Topics: Analysis of Variance; Anemia, Megaloblastic; Animals; Erythrocyte Count; Erythropoietin; Hypoxia; Male; Methylmalonic Acid; Models, Animal; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Aged, 80 and over; Anemia, Megaloblastic; Drug Resistance; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Folic Acid; Hemoglobins; Humans; Male; Recombinant Proteins; Renal Dialysis; Vitamin B 12

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.

Topics: Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Megaloblastic; Antineoplastic Combined Chemotherapy Protocols; beta-Thalassemia; Bone Marrow Transplantation; Erythrocyte Indices; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Feedback; Folic Acid; Hodgkin Disease; Humans; Iron; Kidney; Receptors, Transferrin; Transplantation Conditioning; Vitamin B 12

Topics: Adult; Aged; Anemia, Megaloblastic; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Folic Acid; Humans; Male; Middle Aged; Radioimmunoassay; Reticulocyte Count; Reticulocytes; Vitamin B 12

Topics: Anemia, Megaloblastic; Erythropoietin; Humans; Vitamin B 12

In order to further study the relation between transferrin receptor and erythropoiesis we examined serum receptor levels in megaloblastic anemia, which is the classic example of ineffective erythropoiesis. We studied 33 patients with unequivocal cobalamin deficiency, only 22 of whom were anemic. High serum transferrin receptor levels were found in 12 patients, all of whom were anemic and had high lactate dehydrogenase (LDH) levels; in contrast, only 10 of the 21 patients with normal receptor levels were anemic. Receptor correlated most strongly with LDH (r = 0.573, p < 0.001) and, inversely, with hemoglobin values (r = -0.560, p < 0.001); it also correlated with ferritin and total bilirubin levels, but not with cobalamin, MCV or erythropoietin. No association was found with the hemolytic component of megaloblastic anemia, represented indirectly by haptoglobin levels. Changes induced by cobalamin therapy were also examined in 13 patients. Transferrin receptors rose in all 6 patients who initially had high levels and in 2 of 3 patients who had borderline levels, but not in the 4 patients with initially normal levels. The receptor levels began to rise within 1-3 days, peaked at about 2 weeks and returned to normal at about the 5th wk. The findings indicate that serum transferrin receptor levels reflect the severity of the megaloblastic anemia. The elevated receptor levels rise further with cobalamin therapy, however, as effective erythropoiesis replaces ineffective erythropoiesis, and these persist until the increased erythropoiesis returns to normal.

Topics: Anemia, Megaloblastic; Bilirubin; Biomarkers; Blood Volume; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Receptors, Transferrin; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

Patients with various types of anaemia, but with comparable haemoglobin levels, show a wide range of serum erythropoietic activity. We have developed a method for the fractionation of serum by HPLC followed by bioassay of the individual fractions, using the mouse spleen cell microassay. Up to three distinct peaks of erythropoietic activity corresponding to molecular weights (MW) greater than 300,000, 250,000-300,000 and 40,000 have been found in serum from both normal and anaemic subjects. The erythropoietic profiles of the sera examined differ markedly in anaemias of different aetiology. The chemical nature and the physiological significance of the stimulators remain to be investigated.

Topics: Adolescent; Aged; Anemia; Anemia, Aplastic; Anemia, Megaloblastic; Animals; Biological Assay; Chromatography, High Pressure Liquid; Erythropoietin; Female; Hemoglobins; Humans; Leukemia; Male; Mice; Mice, Inbred C57BL; Middle Aged; Spleen