losartan-potassium and Pancytopenia

During the past 15 years, important progress has been made in the understanding of the biology and prognosis of myelodysplastic syndrome (MDS). MDS is a clonal disorder characterized by ineffective hematopoiesis, which can lead to either fatal cytopenias or acute myelogenous leukemia (AML). Risk-adapted treatment strategies were established because of the high median age (60-75 years) of the MDS patients and the individual history of the disease (number of cytopenias, cytogenetic changes, transfusion requirements). Allogeneic bone marrow transplantation currently offers the only potentially curative treatment, but this form of therapy is not available for the typical MDS patient, who is >60 years of age. Therapy with erythropoietin and G-CSF has improved the quality of life of selected patients. The development of small molecules directed against specific molecular targets with minimal adverse effects is the hope for the future. Innovative uses of immunomodulatory agents and the optimizing of cytotoxic treatment should continue to help in the treatment of MDS.

Topics: Aged; Bone Marrow Transplantation; Cause of Death; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Middle Aged; Myelodysplastic Syndromes; Pancytopenia; Prognosis; Survival Rate

The myelodysplastic syndromes are a heterogeneous family of hematologic disorders characterized by ineffective hematopoiesis. Because of the interpatient variability regarding prognosis and morbidity, management of myelodysplastic syndromes continues to be a challenge to clinical hematologists. Pancytopenia and defective function of neutrophils and platelets carry a high risk of infectious or hemorrhagic complications. Erythropoietin is perhaps the most commonly used therapeutic option, second only to transfusion; improvement of erythropoiesis is seen in approximately 20% of patients, mainly in those with relatively preserved erythroid function and no or low transfusion requirements. Coadministration of erythropoietin with either granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor may increase the response rate up to 50%. Although prophylactic administration of granulocyte- or granulocyte-macrophage colony-stimulating factor cannot be recommended, treatment of febrile neutropenia might benefit from administration of granulocyte- or granulocyte-macrophage colony-stimulating factor in addition to antibiotics.

Topics: Apoptosis; Cytokines; Erythropoietin; Hematopoietic Stem Cell Mobilization; Humans; Myelodysplastic Syndromes; Pancytopenia; Risk Factors

The phosphorylated aminothiol agent amifostine (Ethyol) protects bone marrow and other tissues from toxicity due to ionizing radiation and antineoplastic drugs, and stimulates progenitors from normal and myelodysplastic bone marrow. Contrasting results have been published so far on the effectiveness of amifostine in correcting cytopenia in patients with myelodysplastic syndromes (MDS).. In a pilot phase II study we treated 26 patients with low risk MDS (13 RA, 2 RARS, 2 CMML, 9 RAEB with blasts < 10%) with amifostine (200 mg/m(2 )x 3/week for 4 weeks).. Hemoglobin concentration, reticulocyte, neutrophil and platelet counts increased respectively in 6 (23%), 11 (42%), 13 (50%) and 9 (34%) of patients. Red cell transfusions were reduced (> 50%) in 4/26 patients and abolished in 1/26. Unexpectedly a significant decrease in soluble transferrin receptor level at week 4 of therapy, compared to the basal level (p<0.04), was observed in the whole population of patients.. Amifostine can ameliorate cytopenia in some patients with MDS, with few and mild side effects. Neutropenia is more likely to be corrected than anemia or thrombocytopenia. Mechanisms underlying this biological effect remain to be clarified.

Topics: Aged; Aged, 80 and over; Amifostine; Blood Cell Count; Erythropoietin; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Pancytopenia; Pilot Projects; Radiation-Protective Agents; Receptors, Transferrin; Thrombopoietin

Ectopic pregnancy (EP) is an emergency condition in the gynecologic field. Methotrexate (MTX) is a drug of choice for the medical treatment of EP. Severe adverse events are rare among patients treated with MTX for this condition.. We describe a woman with severe multi-organ involvement experiencing about six days of instability after treatment with just a single-dose MTX for EP. This life-threatening condition is not common with a single dose of MTX. A 30-year-old healthy woman was treated medically with MTX for an EP. Three days later the patient was admitted to the emergency department of our hospital with generalized pustular rashes, alopecia, hyperpigmentation, nausea and vomiting, oral ulcers, and raised Creatinine level. Four days later due to pancytopenia, fever, and loss of consciousness, she was transferred to the intensive care unit and was intubated.. After 38 days of hospitalization, treatment was successful with leucovorin and supportive care and the patient's symptoms and clinical manifestations were regressed.

Topics: Abortifacient Agents, Nonsteroidal; Adult; Alopecia; Anti-Bacterial Agents; Drug Hypersensitivity; Erythropoietin; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Hyperpigmentation; Meropenem; Methotrexate; Pancytopenia; Platelet Transfusion; Pregnancy; Pregnancy, Ectopic; Pseudomonas aeruginosa; Pseudomonas Infections; Unconsciousness

In recent years, we have detected autoantibodies in bone marrow (BM) hemopoietic cells in some patients with idiopathic cytopenia of undetermined significance (ICUS), termed immunorelated pancytopenia (IRP). However, we know little about the targets of these autoantibodies.. Twenty-six newly diagnosed IRP patients with IgG autoantibody on nucleated erythrocytes and 20 healthy donors as controls were enrolled in this study. The serum erythropoietin (EPO) level was examined by ELISA. Expression of EPO receptor (EPOR) and IgG autoantibody on the membrane of nucleated erythrocytes were detected by flow cytometry before and after autoantibody stripping.. The serum EPO level of the untreated patients was 199.9 ± 106.4 mIU/mL, which was significantly higher than that of normal controls (13.2 ± 8.41 mIU/mL, p < 0.01). EPOR expression on nucleated erythrocytes in the patients was 1.38 ± 0.73%, lower than that of normal controls (2.33 ± 1.73%), but there was no significant difference; EPOR in these patients was inversely correlated with IgG autoantibody on erythrocytes (r = -0.479, p = 0.013). The regression equation was Y = 0.116-0.479X; EPOR expression on the membrane increased significiantly (5.63 ± 4.99%, p < 0.01) after stripping the autoantibodies. After immunosuppressive treatment, median hemoglobin increased from 72 g/L to 98 g/L, and median reticulocytes increased from 1.46% to 3.56%.. IgG autoantibodies might block or competitively inhibit EPOR on nucleated erythrocytes in some cases of ICUS.

Topics: Adolescent; Adult; Autoantibodies; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Erythroblasts; Erythropoietin; Female; Flow Cytometry; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Middle Aged; Pancytopenia; Predictive Value of Tests; Receptors, Erythropoietin; Treatment Outcome; Young Adult

Topics: Acute Kidney Injury; Adult; Blood Component Transfusion; Bone Marrow; Cell Lineage; Combined Modality Therapy; Darbepoetin alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Pancytopenia; Pericarditis; Prednisone; Proteinuria; Recombinant Proteins

Serous atrophy or gelatinous transformation of the bone marrow (GMT), often seen with severe nutritional deprivation in Anorexia Nervosa (AN), is characterized by hypocellularity and patchy or diffuse replacement of the bone marrow with hyaluronic acid-like mucopolysaccharide material. Treatment with nutritional support alone is often temporary due to the relapsing nature of AN. We present the case of a patient with pancytopenia due to GMT who had multiple prior hospitalizations for infections and blood transfusions. Nutritional support was inadequate in restoring her bone marrow function. She was successfully treated with hematopoietic growth factors and achieved a sustained hematopoietic recovery. In addition, use of growth factors resulted in a 91% reduction in the cost of health care delivered to this patient.

Topics: Adult; Anorexia Nervosa; Bone Marrow; Bone Marrow Diseases; Darbepoetin alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Cell Growth Factors; Humans; Pancytopenia; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome

Topics: Adult; Anemia; Erythropoietin; Female; Humans; Myelodysplastic Syndromes; Pancytopenia; Pregnancy; Pregnancy Complications, Neoplastic; Recombinant Proteins

Multicytokine therapy may be useful to counteract radiation-induced myelosuppression. We assessed the stem cell factor + glycosylated erythropoietin + pegylated granulocyte colony-stimulating factor combination (SEG) as an emergency treatment. SEG in highly irradiated monkeys efficacy appeared to be restricted to granulopoiesis. Early administration of Erythropoietin did not prevent radiation-induced anemia.

Topics: Animals; Blood Transfusion; Cytokines; Drug Evaluation, Preclinical; Drug Therapy, Combination; Emergencies; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Interleukin-3; Macaca fascicularis; Membrane Proteins; Pancytopenia; Polyethylene Glycols; Radiation Injuries, Experimental; Recombinant Proteins; Stem Cell Factor; Thrombopoietin

Topics: Adult; Antiviral Agents; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Iron; Male; Pancytopenia; Polyethylene Glycols; Receptor, Interferon alpha-beta; Recombinant Proteins; Ribavirin; Signal Transduction

Erythropoiesis in the adult mammal depends critically on erythropoietin, an inducible cytokine with pluripotent effects. Erythropoietin gene expression increases under conditions associated with lowered oxygen content such as anemia and hypoxia. HIF-1alpha, the founding member of the hypoxia-inducible factor (HIF) alpha class, was identified by its ability to bind and activate the hypoxia-responsive enhancer in the erythropoietin regulatory region in vitro. The existence of multiple HIF alpha members raises the question of which HIF alpha member or members regulates erythropoietin expression in vivo. We previously reported that mice lacking wild-type HIF-2alpha, encoded by the EPAS1 gene, exhibit pancytopenia. In this study, we have characterized the etiology of this hematopoietic phenotype. Molecular studies of EPAS1-null kidneys reveal dramatically decreased erythropoietin gene expression. EPAS1-null as well as heterozygous mice have impaired renal erythropoietin induction in response to hypoxia. Treatment of EPAS1-null mice with exogenous erythropoietin reverses the hematopoietic and other defects. We propose that HIF-2alpha is an essential regulator of murine erythropoietin production. Impairments in HIF signaling, involving either HIF-1alpha or HIF-2alpha, may play a prominent role in conditions involving altered hematopoietic or erythropoietin homeostasis.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Erythropoietin; Female; Gene Expression; Hematopoiesis; Hypoxia; Kidney; Male; Mice; Mice, Mutant Strains; Pancytopenia; Phenotype; RNA, Messenger; Trans-Activators

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticulate skin pigmentation, nail dystrophy, mucosal leucoplakia, and bone marrow failure. Pancytopenia is difficult to manage in patients with this disorder. We describe a 13-month-old-boy who presented with reticulate skin lesions, paleness, and hepatosplenomegaly. Anemia and leukopenia developed by the age of 43 months. The patient was treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) (5 microg/kg/d, subcutaneously) for 19 months and erythropoietin (150 U/kg 3 days in a week, subcutaneously) for 8 months, with excellent neutrophil and hemoglobin response. Recurrent infections were not developed after starting GM-CSF, and packed red blood cell transfusion was not given to the patient after starting erythropoietin. GM-CSF combined with erythropoietin may be used in the treatment of bone marrow failure in patients with DC without an HLA-identical donor.

Topics: Blood Cell Count; Bone Marrow; Child, Preschool; Deferoxamine; Disease Susceptibility; Dyskeratosis Congenita; Erythropoietin; Ferritins; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Pancytopenia; Respiratory Tract Infections

Topics: Aged; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Carcinoma, Hepatocellular; Cell Differentiation; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Humans; Hypersplenism; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Myelodysplastic Syndromes; Pancytopenia; Reticulocyte Count; Reticulocytes

Transient treatment with cytokines appears to improve hematopoietic function in Fanconi anemia; however, the effectiveness or adverse effect of long-term treatment is not known. The mitomycin C-treated Fancc(-/-) mouse provides a valuable model to address long-term efficacy of such treatment. Fancc(-/-) mice injected with granulocyte colony-stimulating factor, erythropoietin, or both cytokines showed a delay in mitomycin C (MMC)-induced bone marrow (BM) failure compared to untreated mice. However, long-term cytokine exposure followed by MMC challenges did not protect mice from the reduction of peripheral blood counts or the number of early myeloid progenitors. These results suggest that cytokine treatment may be beneficial only in the short-term, while long-term treatment is not protective for BM aplasia.

Topics: Animals; Bone Marrow; Erythrocyte Count; Erythropoietin; Fanconi Anemia; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cells; Leukocyte Count; Mice; Mice, Inbred BALB C; Mice, Knockout; Mitomycin; Pancytopenia; Survival Rate

We reported a rare case of pancytopenia caused by allopurinol. A 61-year-old man was first admitted in May 1993, because of thrombocytosis. He had suffered from chronic glomerulonephritis. He was administered allopurinol for hyperuricemia from March 1993. On first admission the laboratory findings revealed leukocytosis (10,100/microliter) and thrombocytosis (971 x 10(3)/microliter) in the peripheral blood. Myelofibrosis was strongly suspected due to increased number of MgK and reticular fiber in the bone marrow. Two months later, he readmitted due to pancytopenia (WBC 1,300/microliter, Hb 6.2g/dl, Plt 10 x 10(3)/microliter). His bone marrow showed markedly hypocellular. Because we suspected that pancytopenia was induced by allopurinol, we discontinued allopurinol and administered oxymetholone, G-CSF, and EPO, WBC, RBC, and platelet count had been recovered about one and half months later. In vitro co-culture indicated that CFU-G, E, and Meg in the bone marrow cells after recovery from pancytopenia were markedly suppressed in the presence of patient's serum and oxipurinol. Pancytopenia due to allopurinol was reported to be rare, and some authors showed that it will sometimes be fatal. Because pancytopenia of this case had been recovered in a relatively short time with cytokine therapy, it was thought to be effective for pancytopenia due to drug like this case.

Topics: Allopurinol; Antimetabolites; Drug Therapy, Combination; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Myeloproliferative Disorders; Oxymetholone; Pancytopenia; Recombinant Proteins

An 11-year-old castrated male Dachshund was determined to have pancytopenia on the basis of results of CBC and bone marrow cytologic examination. Pancytopenia was believed to have resulted from administration of captopril, which had been administered for treatment of chronic mitral insufficiency, because other causes of pancytopenia were not found. Treatment consisted of discontinuing captopril and stimulating the bone marrow with recombinant human erythropoietin and granulocyte colony-stimulating factor. Although neutralizing antibodies will develop against the heterologous human protein, recombinant human granulocyte colony-stimulating factor should be considered for short-term treatment of neutropenias associated with adverse drug reactions, canine parvovirus infections, and bone marrow suppression from primary bone marrow disease, cancer chemotherapy, or total body irradiation before bone marrow transplantation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biopsy, Needle; Blood Cell Count; Bone Marrow; Captopril; Chronic Disease; Dog Diseases; Dogs; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematocrit; Male; Mitral Valve Insufficiency; Pancytopenia; Recombinant Proteins

Topics: Anemia, Refractory; Blood Transfusion; Chronic Disease; Combined Modality Therapy; Erythropoietin; Hepatitis C; Humans; Male; Middle Aged; Pancytopenia; Recombinant Proteins; Recurrence; Remission Induction; Splenectomy

Topics: Erythropoietin; Hemochromatosis; Humans; Pancytopenia; Recombinant Proteins; Renal Dialysis

In patients with hairy cell leukemia (HCL), we measured serum levels of monocyte colony-stimulating factor (M-CSF), interleukin-6 (IL-6), and erythropoietin during various degrees of pancytopenia characteristic for this disease. Serial sera from 12 HCL patients during various stages of the disease were analyzed. No correlation was found between the levels of M-CSF or IL-6 and the numbers of circulating monocytes or platelets, normal values of M-CSF (4 to 10 mg/l), and IL-6 (3-50 U/ml) being detected during all stages of the disease. In contrast, erythropoietin levels were inversely related with the hemoglobin concentration (r = -0.79), indicating the presence of a normal feedback mechanism for this factor in patients with HCL.

Topics: Erythropoietin; Humans; Interleukin-6; Leukemia, Hairy Cell; Macrophage Colony-Stimulating Factor; Pancytopenia; Time Factors

Human urinary erythropoietin has been purified to homogeneity. The seven-step procedure yielded a preparation with a potency of 225,000 U/mg protein. SDS-polyacrylamide gel electrophoretic analysis of the purified hormone revealed a single protein band with a molecular weight of about 35,000 that migrated with the biological activity. As to its stability, the purified hormone retained its activity in the presence of 0.001% Tween 20.

Topics: Anemia, Aplastic; Animals; Biological Assay; Chromatography, High Pressure Liquid; Drug Stability; Electrophoresis, Polyacrylamide Gel; Erythropoietin; Humans; Hydrogen-Ion Concentration; Molecular Weight; Pancytopenia; Rats; Rats, Inbred Strains

Altogether 21 patients were examined for an erythropoiesis inhibitor contained by the IgG fraction of the blood plasma. All these patients suffered from hemopoiesis depression. The inhibitor identified in the immunoglobulin fraction of the blood plasma of 40% of the patients manifested itself at the stage of erythroid precursors of bone marrow cells. The role of the humoral inhibitor in the development of erythropoietic disorders in these patients is under discussion.

Topics: Animals; Blood Proteins; Erythropoiesis; Erythropoietin; Female; Humans; Immunoglobulin G; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Pancytopenia; Polycythemia

A 60-year-old patient with a myelodysplastic syndrome (MDS) corresponding to refractory anemia with an increase in blast cells (RAEB) was treated with granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO) for severe symptomatic pancytopenia. During the GM-CSF treatment a distinct increase in granulocytes was observed, but the reticulocytes and thrombocytes decreased to the point where treatment had to be discontinued after eight days. After subsequent treatment with EPO the reticulocyte count rose from 0% to 2%. However, this rise alone was insufficient to decrease the number of blood transfusions required. The thrombocyte count rose to the original values after the cessation of GM-CSF therapy while continuing treatment with EPO. Bone marrow investigations were performed before and after GM-CSF treatment and indicated a distinct increase in the myeloid precursor cells after therapy, without an increase in blasts. On the other hand, an obvious decrease in erythro- and megakaryopoiesis was observed.

Topics: Anemia, Refractory, with Excess of Blasts; Blood Platelets; Colony-Stimulating Factors; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Male; Middle Aged; Pancytopenia; Stem Cells

3 different methods, (1) assays of CFU-Cs and CFU-Es, (2) responsiveness of CFU-Cs and CFU-Es to low doses of CSF and ESF, respectively and (3) effects of ALG on CFU-C colony formation in vitro, were used to evaluate the quantitative and qualitative defects of stem cells in 28 patients with aplastic anaemia. Some patients with aplastic anaemia who had attained complete remission several years previously, exhibited severely depressed in vitro CFU-C colony formation. This suggests that the defect persists for a long time after clinical complete remission. Residual marrow CFU-Cs and CFU-Es did not have defective responses to the humoral stimulating factors, CSF and ESF. No patient showed a rise of colony number after treatment with ALG in vitro.

Topics: Anemia, Aplastic; Colony-Forming Units Assay; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Erythropoietin; Female; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Pancytopenia

In the last decade a large increase of our basic understanding concerning erythropoietin and the regulation of erythropoiesis has led to improved methods for the cell culture of human bone marrow cells. These culture methods in turn have been applied to bone marrow failures with a remarkable increase in our knowledge of the pathogenesis of some of these conditions, particularly the aplasias. The pathogenesis of pure red cell aplasia has been elucidated, and 60% of these patients have been shown to respond to cytotoxic, immunosuppressive treatment. Bone marrow transplantation has proved to be very helpful in the treatment of aplastic anemia and has provided impetus for increased knowledge concerning the pathogenesis of the aplasia. Some of these patients may have suppression of marrow hematopoiesis by the marrow T-cells and can be successfully treated with antilymphocyte globulin or high-dose prednisolone. The future looks bright for further clinical advances concerning the bone marrow failures, but more must be learned about the pathogenesis of these anemias if improved methods of treatment are to be developed.

Topics: Aged; Anemia, Aplastic; Anemia, Sideroblastic; Animals; Bone Marrow; Cyclophosphamide; Erythropoiesis; Erythropoietin; Female; Humans; Pancytopenia; Prednisone; Primary Myelofibrosis