losartan-potassium and Anemia--Macrocytic

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Myelophthisic; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Erythrocyte Count; Erythropoiesis; Erythropoietin; Reticulocytes

Topics: Anemia, Macrocytic; Complement System Proteins; Erythropoietin; Folic Acid; Humans; Leukemia; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Blood Platelets; Eosinophilia; Epoetin Alfa; Erythropoietin; Humans; Iron; Leukemia; Polycythemia Vera; Vitamin B 12

Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug's effects on clonal evolution remain unknown. We investigated recurrent mutations by next-generation sequencing in 94 non-del(5q) MDS patients randomized in the GFM-Len-Epo-08 clinical trial to lenalidomide or lenalidomide plus epoetin β. Clonal evolution was analyzed after 4 cycles of treatment in 42 cases and reanalyzed at later time points in 18 cases. The fate of clonal architecture of single CD34(+)CD38(-) hematopoietic stem cells was also determined in 5 cases. Mutation frequency was >10%: SF3B1 (74.5%), TET2 (45.7%), DNMT3A (20.2%), and ASXL1 (19.1%). Analysis of variant allele frequencies indicated a decrease of major mutations in 15 of 20 responders compared with 10 of 22 nonresponders after 4 cycles. The decrease in the variant allele frequency of major mutations was more significant in responders than in nonresponders (P < .001). Genotyping of single CD34(+)CD38(-) cell-derived colonies showed that the decrease in the size of dominant subclones could be associated with the rise of founding clones or of hematopoietic stem cells devoid of recurrent mutations. These effects remained transient, and disease escape was associated with the re-emergence of the dominant subclones. In conclusion, we show that, although the drug initially modulates the distribution of subclones, loss of treatment efficacy coincides with the re-expansion of the dominant subclone. This trial was registered at www.clinicaltrials.gov as #NCT01718379.

Topics: Aged; Anemia, Macrocytic; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Chromosome Deletion; Chromosomes, Human, Pair 5; Clonal Evolution; Clone Cells; DNA Mutational Analysis; Erythropoietin; Female; Humans; Lenalidomide; Male; Myelodysplastic Syndromes; Recombinant Proteins; Thalidomide; Treatment Outcome

Topics: Aged; Anemia, Macrocytic; Bone Marrow; Erythropoietin; Fatigue; Humans; Lenalidomide; Myelodysplastic Syndromes; Stem Cell Transplantation; Thalidomide

The anomalous EVI1 rearrangements/t(3;3)(q21;q26) is more frequently found in myelocytic malignancies. 5q- syndrome is a newly defined subtype of myelodysplastic syndrome (MDS) first proposed by the World Health Organization in 2001. Cases of acute lymphocytic leukemia (ALL) with 5q- anomaly or t(3;3)/EVI1 rearrangement have rarely been reported. We report a rare 5q- syndrome case which ultimately transformed to acute lymphocytic leukemia accompanied by a secondary cytogenetic anomaly of t(3;3)(q21;q26) and EVI1 rearrangement around 3 years after the diagnosis of 5q- syndrome. This rare case suggests that the 5q- clone of MDS may originate from a multipotent cell with a capacity to differentiate toward both myeloid and lymphoid lineages. It also indicates that although the t(3;3)/EVI1 rearrangement is mostly related to myelocytic neoplasms, the t(3;3)/EVI1-rearrangement may also play an important role in the development of ALL. The results of the necessary tests must be analyzed sufficiently prior to making a final diagnosis.

Topics: Adult; Anemia, Macrocytic; Blood Transfusion; Bone Marrow; Cell Differentiation; Cell Lineage; Chromosome Deletion; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 5; Disease Progression; DNA-Binding Proteins; Erythropoietin; Fatal Outcome; Fatigue; Humans; Immunophenotyping; Karyotype; Male; MDS1 and EVI1 Complex Locus Protein; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogenes; Testosterone; Thalidomide; Transcription Factors

While folic acid deficiency causes macrocytic anaemia in non-renal patients, the relevance of altered folate metabolism in anaemia of end-stage renal disease and its response to rHu-EPO is less clear.. Ten haemodialysis patients with macrocytic anaemia due to dietary folic acid deficiency were compared to 10 matched (age, duration of dialysis, degree of anaemia) patients with normocytic normochromic anaemia. Nineteen patients received erythropoietin-alpha intravenously thrice weekly. The study design was a prospective crossover (ABA) comparison of the effects of intravenously administered high doses of folic acid on haemoglobin levels and EPO doses, with 6 months active supplementation (B) and two periods of 6 months duration each without folic acid supplementation (A).. The two patient groups did not differ at recruitment. Red blood cell folate levels were normal in patients with normocytic anaemia, but they were subnormal in all patients with macrocytic anaemia. Compared to the first period without folic acid supplementation, patients with macrocytic anaemia had significantly higher haemoglobin levels despite lower EPO doses after 6 months high-dose folic acid, and red cells had become normocytic. The removal of folic acid supplementation resulted in re-occurrence of macrocytosis and in a significantly lower response to rHu-EPO. In contrast, high-dose folic acid supplementation had no effect on response to rHu-EPO in patients with normocytic anaemia.. Folic acid deficiency may occur in elderly haemodialysis patients with poor dietary folate intake without regular oral supplementation and may cause hyporesponsiveness to rHu-EPO. Macrocytosis is a simple and cheap indicator for folate deficiency in end-stage renal disease patients on maintenance dialysis.

Topics: Adult; Aged; Anemia, Macrocytic; Case-Control Studies; Erythropoietin; Female; Folic Acid Deficiency; Follow-Up Studies; Hematopoiesis; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Probability; Recombinant Proteins; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

Topics: Adolescent; Adult; Anemia, Macrocytic; Arthritis, Juvenile; Child; Child, Preschool; Erythropoietin; Female; Humans; Male; Pilot Projects; Recombinant Proteins

Congenital hypoplastic (Diamond-Blackfan) anemia is a rare macrocytic anemia, generally presenting during infancy or childhood. The condition usually occurs sporadically or in a pattern consistent with autosomal recessive inheritance, although autosomal dominant transmission has been proposed in some kindreds. We report the largest known kindred of congenital hypoplastic anemia, with at least 7 affected individuals over 3 generations, and propose that studies of this kindred may be useful for identifying the mechanism by which their genetic abnormality results in congenital hypoplastic anemia. Erythropoietic investigations on relatives show no inhibitors of erythropoiesis in serum, T-lymphocytes, or macrophages. Their erythroid progenitor cells (CFU-E and BFU-E) were generally quantitatively normal, and were capable of rapid proliferation, as judged by cell-cycle shortening. However, their erythroid progenitors displayed a relative insensitivity to recombinant erythropoietin, and produced relatively few normoblasts per erythroid progenitor cell. We propose that these and subsequent studies may be helpful in selecting candidate genes responsible for the molecular defect in this kindred.

Topics: Adolescent; Adult; Anemia, Aplastic; Anemia, Macrocytic; Child, Preschool; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Humans; Male; Pedigree; Recombinant Proteins

The effects of recombinant human erythropoietin (rHuEPO) on anaemic W/Wv and Sl/Sld mice were investigated. rHuEPO was injected every day for a week in doses up to 86,000 iu/kg. Wv/+ and Sld+ mice, which have genetically a weak anaemia, received 17 or 86 iu/kg of rHuEPO and showed dose-dependent increases in haemoglobin, PCV, RBC and reticulocytes to the same extent as that in normal mice. W/Wv mice also showed increases in the haematological parameters in response to 8600 iu/kg of rHuEPO but the dose was much higher than that for normal mice. A reticulocyte increase in W/Wv mice appeared later than in normal mice and was not sustained for 2 weeks even though the rHuEPO treatment was continued. Sl/Sld mice, however, did not show any significant haematological effect from doses up to 86,000 iu/kg. In both W/Wv and Sl/Sld mice receiving 8600 and 86,000 iu/kg of rHuEPO, respectively, an increase in splenic or bone marrow CFU-E was observed regardless of the defect in their haemopoietic systems. The plasma erythropoietin (EPO) level in W/Wv and Sl/Sld mice was inversely correlated with the haemoglobin, indicating that EPO production was not influenced by the haemopoietic defect and was regulated by the hypoxic properties of the anaemia. These results indicate that a large dose of exogenous rHuEPO is effective for the anaemia in W/Wv mice caused by a stem cell defect but not for the anaemia in Sl/Sld mice caused by a defective microenvironment.

Topics: Anemia, Macrocytic; Animals; Bone Marrow Transplantation; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Erythrocyte Count; Erythroid Precursor Cells; Erythropoietin; Hemoglobins; Humans; Male; Mice; Recombinant Proteins; Reticulocytes

We have compared the response of mice heterozygous for the Slj allele-which have a stromal defect resulting in mild macrocytic anemia-and their normal +/+ littermates to manipulations of the erythron to further characterize the effects of the Slj allele on hemopoiesis. CFU-S kinetics in Slj/+ mice following plethorization or induction of anemia did not differ from similarly treated +/+ littermates. Under all circumstances, however, Slj/+ mice had a smaller splenic CFU-S population than similarly treated +/+ mice. Slj/+ and +/+ mice responded similarly to induction of hemolytic anemia with a large rise in 59Fe incorporation in spleen and blood. Hypertransfused Slj/+ mice were shown to have a diminished response to exogenous erythropoietin in spleen and blood as compared with their +/+ littermates. We conclude that the regulation of CFU-S kinetics in mutant Slj/+ mice is not anomalous as has been reported to be the case in Sl/Sld mice. The defective stromal tissue of Slj/+ mice, however, does not support a normal-sized CFU-S population, which leads to decreased influx of progenitor cells into the erythropoietin-responsive cell compartment, causing the diminished response of plethorized Slj/+ mice to exogenous erythropoietin.

Topics: Anemia, Hemolytic; Anemia, Macrocytic; Animals; Blood Transfusion; Bloodletting; Bone Marrow; Erythropoietin; Female; Hematopoiesis; Hematopoietic Stem Cells; Male; Mice; Mice, Mutant Strains; Phenylhydrazines; Polycythemia; Spleen

Mice homozygous for Hertwig's anemia, an/an, have a mild macrocytic anemia and are refractory to the potentially curative action of exogenously administered erythropoietin (EP). Both red and white blood cell numbers are decreased. One possible explanation is that a precursor stem cell population is in short supply. We have examined this possibility through comparisons of CFU-S, BFU-E, and CFU-E numbers in an/an and +/+ mouse bone marrow. The response of erythroid-committed stem cells to EP in vitro has also been determined. Our findings suggest that EP resistance is due to diminished numbers rather than decreased EP sensitivity of responsive cells. In mice with Hertwig's anemia, the relative numbers of both BFU-E and CFU-E are reduced. The erythroid-committed stem cells are more severely affected than their progenitors, the CFU-S. The data show that cells are lost during the progressive differentiation from stem cell to erythrocyte.

Topics: Anemia, Macrocytic; Animals; Cell Differentiation; Colony-Forming Units Assay; Erythropoietin; Hematopoietic Stem Cells; Homozygote; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Radiation Chimera

Adult SI/SI-d mutant mice have severe macrocytic, normochromic anemia. Moreover these animals are unresponsive to the stimulation of erythropoietin in vivo. By means of a bone marrow cell suspension culture system, the present investigation shows that in adult SI/SI-d marrow, there are cells capable of responding in vitro to erythropoietin in a normal fashion. Moreover, the erythropoietin present in SI/SI-d serum is biologically active in vitro without any prior biochemical modification. These observations support the suggestion that there is a defect in differentiation in the erythroid cell lines of SI/SI-d mice in vivo due to an abnormal hemopoietic microenvironment.

Topics: Anemia, Macrocytic; Animals; Bone Marrow Cells; Cells, Cultured; Erythropoiesis; Erythropoietin; Femur; Heme; Iron Radioisotopes; Mice; Mutation; Sheep

Topics: Agranulocytosis; Anemia, Aplastic; Anemia, Macrocytic; Bone Marrow Examination; Bone Neoplasms; Breast Neoplasms; Dihydrotestosterone; Erythropoiesis; Erythropoietin; Female; Hepatitis; Humans; Iron; Iron Radioisotopes; Male; Oxymetholone; Prednisolone; Sepsis; Transfusion Reaction

Topics: Anemia; Anemia, Macrocytic; Animals; Cell Differentiation; Erythropoiesis; Erythropoietin; Glycosaminoglycans; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Histocytochemistry; Mice; Mice, Inbred Strains; Regional Blood Flow; Spleen; Transplantation, Homologous

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Bilirubin; Erythropoietin; Humans; Iron; Neoplasms

Topics: Anemia, Macrocytic; Animals; Atmospheric Pressure; Blood Volume; Bone Marrow Cells; Erythropoiesis; Erythropoietin; Genotype; Hematocrit; Hemorrhage; Hypoxia; Mice; Mice, Inbred Strains; Mutation; Phenylhydrazines; Spleen

Topics: Anemia, Macrocytic; Animals; Bone Marrow Transplantation; Cell Differentiation; Cells, Cultured; Chromosomes; Erythropoietin; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mice; Radiation Chimera; Spleen; Transplantation, Homologous

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Diagnosis, Differential; Erythrocytes; Erythropoietin; Half-Life; Hemorrhage; Humans; Iron; Neoplasms; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Macrocytic; Animals; Bone Marrow; Bone Marrow Diseases; Daunorubicin; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Phenylhydrazines; Rabbits; Radiation Effects

Topics: Aged; Anemia, Macrocytic; Calcium; Duodenal Ulcer; Erythropoietin; Hemoglobinometry; Humans; Iron; Leukocyte Count; Male; Phosphorus Isotopes; Polycythemia Vera; Postgastrectomy Syndromes; Uric Acid; Vitamin B 12

Topics: Anemia, Macrocytic; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Erythrocytes; Erythropoietin; Female; Friend murine leukemia virus; Genotype; Hypoxia; Male; Mice; Spleen; Transplantation, Homologous; Virulence

Topics: Anemia, Macrocytic; Animals; Erythropoietin; Gastrointestinal Hemorrhage; Mice

Topics: Adolescent; Anemia, Hypochromic; Anemia, Macrocytic; Animals; Blood; Blood Cell Count; Blood Chemical Analysis; Erythropoietin; Female; Humans; Hypothyroidism; Iodine Isotopes; Male; Middle Aged; Rabbits; Rats; Thyroid Hormones; Thyroidectomy

Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Anemia, Macrocytic; Blood Platelets; Bone Marrow Cells; Drug Therapy; Epoetin Alfa; Erythropoietin; FIGLU Test; Folic Acid; Folic Acid Deficiency; Glutamates; Hemoglobins; Humans; Infant; Infusions, Parenteral; Injections, Intravenous; Iron; Iron-Dextran Complex; Megakaryocytes; Reticulocytes; Thrombocytopenia; Thrombocytosis; Vitamin B 12